A University of Manchester scientist has been awarded the prestigious by the Royal Society for his work documenting the history of biology as both an author and a broadcaster.

The medal, given for excellence in a subject relating to the history, philosophy or social function of science, was awarded to Professor Matthew Cobb last week.

Professor Cobb joined The University of Manchester in 2002 as a lecturer in animal behaviour; he is currently a Professor of Zoology in the Division of Evolution, Infection and Genomics, but will shortly retire, becoming Professor Emeritus.

While most of Professor Cobb’s research has been on behaviour and communication in animals, his Royal Society medal is in recognition of his contribution to the history of science.

Professor Cobb said: “This is a tremendous honour for me – the Medal is the fusion of three awards, one of which goes back 80 years, and has been won by some extraordinary people.

“It is really quite humbling to be in such company. And a vindication of The University of Manchester’s embrace of multidisciplinarity, and of the School of Biological Sciences’ enthusiasm for its students’ taking courses from the Centre for the History of Science, Technology and Medicine.”

In 2021, Professor Cobb presented a BBC radio series on the history of genetic engineering, He has also presented programmes about the history of academic publishing, the development of CRISPR gene editing, as well as programmes about the origins of animals and the life of the revolutionary scientist Sydney Brenner.

Alongside his BBC series, Professor Cobb is known to a wider audience through his books which have received commercial success. In 2022, he published The Genetic Age: Our Perilous Quest to Edit Life. In 2020, The Idea of the Brain was chosen as one of The Sunday Times' ‘Books of the Year’.

The Wilkins, Bernal and Medawar lectures were originally delivered as three separate lectures, before they were combined under one title in 2007. Previous winners include Melvyn Bragg in 2010, Professor Jim Al-Khalili OBE FRS in 2020, and most recently Professor Sarah Franklin, who in 2023 delivered the lecture, ‘Talking Embryos: Changing Public Perceptions of Embryo Research’.

Professor Cobb’s passions extend beyond science. He has written two books on the French Resistance during World War II, one of which won the Anglo-French Society Award.

For this work he was made a Chevalier dans l’Ordre des Palmes académiques, an award conferred by the French government for significant contributions to the advancement of intellectual, scientific and artistic pursuits.

Professor Cobb is currently finishing a biography about Francis Crick, the co-discoverer of the DNA double helix; Crick’s extraordinary career will potentially inform the subject of Cobb’s Royal Society lecture. The date of his prize lecture is yet to be confirmed.

• To read more on the Royal Society’s 2024 award recipients visit .

Awarded by the not-for-profit Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC), the accreditation is seen as a considerable achievement for the unit and the University. 

91ֱ�� joins 20 other establishments in UK with AAALAC accreditation, though only a handful are from higher education institutions. 

AAALAC evaluates organizations that use animals in research, teaching or testing around the world. Those that meet or exceed AAALAC standards are awarded accreditation. 

Dr Maria Kamper, Director of the unit – also known as the biological services facility (BSF) - said: “This  accreditation is testament to the University’s unwavering commitment to the highest standards of animal welfare and quality in research. 

"I would like to thank every member of the BSF team and the wider University community for their contribution to achieving this milestone. 

“Together, we look forward to building on this success, fostering an environment where excellence in science goes hand in hand with the highest standards of care and ethics." 

The  application process, which took a year, involved drafting a detailed description of the unit’s  animal care and use programme, outlining its practices, protocols, and commitment to animal welfare. 

The report was followed up by a site visit by an AAALAC Council member, accompanied by an ad hoc consultant, who conducted in-depth reviews of the facilities and operations.

Dr Kamper added: "We feel this achievement can only enhance our reputation among our peers, funding bodies, and industry partners as being at the forefront of responsible, cutting-edge research.

“They can rest assured that our dedication to responsible research and animal care is formally recognised by the world’s leading accreditation body for animals in science.

"Though we celebrate this achievement, our commitment to improvement continues, ensuring that our practice reflects the latest in animal welfare and research integrity. “

Patrick Hackett,  Registrar, Secretary and Chief Operating Officer and Establishment Licence Holder at of The University of  91ֱ�� said:  “We are extremely proud to have secured AAALAC accreditation for our University.

“This is a highly prestigious achievement, which is testimony both to our commitment to 91ֱ��’s excellence in animal care and research, and to the significant efforts and success of the BSF team working in partnership with a wide range of other colleagues here.”

• Image  from left to right:  Victoria Perks and  Dr Jo Stanley  join  Registrar, Secretary and Chief Operating Officer and establishment licence holder, Patrick Hackett  who receives the AAALAC accreditation plaque  from  BSF Director Dr Maria Kamper next to  Dr Ian Millar 

Antibiotics are given to kill bad bacteria, however with just one mutation a bacteria can evolve to become resistant to that antibiotic, making common infections potentially fatal.

The new research, published today in the journal , used high-performance computing to simulate more than 8,000 years of bacterial evolution, allowing scientists to predict mechanisms that control mutation rates. They then made more than 15,000 cultures of E. coli in lab conditions to test their predictions - that’s so many that if you lined up all of the bacteria in this study, they would stretch 860,000km, or wrap around the Earth more than 20 times!

The tests revealed that bacteria living in a lowly populated community are more prone to developing antibiotic resistance due to a naturally occurring DNA-damaging chemical, peroxide. In crowded environments, where cells are more densely packed, bacteria work collectively to detoxify peroxide, reducing the likelihood of mutations that lead to antibiotic resistance.

The finding could help develop "anti-evolution drugs" to preserve antibiotic effectiveness by limiting the mutation rates in bacteria.

Lead researcher from The University of Manchester, said: "Antibiotic resistance presents an existential challenge to human health. Bacteria rapidly evolve resistance to the antibiotic drugs we use to treat infections, while new drugs aren’t being developed fast enough to keep up.

“If we can’t keep antibiotics working, routine surgery could be a life-or-death encounter, with common infections becoming untreatable.

“By understanding the environmental conditions that influence mutation rates, we can develop strategies to safeguard antibiotic effectiveness. Our study shows that bacterial mutation rates are not fixed and can be manipulated by altering their surroundings, which is vital on our journey to combat antibiotic resistance."

Peroxide, a chemical found in many environments, is key to this process. When E. coli populations become denser, they work together to lower peroxide levels, protecting their DNA from damage and reducing mutation rates. The study showed that genetically modified E. coli that is unable to break down peroxide had the same mutation rates, no matter the population size. However, when helper cells that could break down peroxide were added, the mutation rate in these genetically modified E. coli decreased.

The research builds on previous findings by group, which indicated that denser bacterial populations experience lower mutation rates. The current study uncovers the specific mechanism behind this phenomenon, highlighting the role of collective detoxification in controlling mutation rates.

The research team, part of the Microbial Evolution Research in 91ֱ�� (MERMan) collective, conducted this extensive study with contributions from researchers at all career stages. The lab work was primarily carried out by a PhD student, alongside six undergraduate and master's students, under the guidance of four lab group leaders.

The researchers from The University of Manchester, along with Loughborough and Birmingham City Universities, revealed a freshly eaten fish still attached to its hook in the beast’s stomach, which probably killed it.

Using specialist software in combination with X-ray and CT scanning, the scientists were able to virtually extract the hook from the mummy, and then construct a replica first in plastic and then cast in its original material, bronze.

The age of the animal mummy - kept at Birmingham Museum and Art Gallery and known by its accession number, 2005.335  –  could be anything from between 2,000 and 3,000 years old, when the practice of mummifying animals was at its peak.

The study funded by the Arts and Humanities Research Council and the Leverhulme Trust is published in the journal Digital Applications in Archaeology and Cultural Heritage.

The croc had swallowed considerable numbers of small stones known as gastroliths while alive to break down of chunks of meat and regulate buoyancy.

The presence of more gastroliths higher up in the digestive tract, say the authors, indicate an attempt to break down the animal’s last meal, and showed it died before they reached its stomach.

The skeletal integrity of the fish also suggests that it was swallowed whole and had not yet been affected by the harsh digestive enzymes present in the first chamber of the crocodile’s stomach or the abrasive action of the gastroliths.

The apparent short time span between the ingestion of the fish and the death of the crocodile also suggest, say the researchers, it was deliberately caught in the wild and processed for mummification as an offering to the crocodile god Sobek shortly afterwards.

Healthy crocodiles were associated with fertility and plentiful agriculture. The Egyptians also believed you could protect yourself from danger by wearing clothing made from the skin of the animal.

Lead author Dr Lidija Mcknight Research Fellow from The University of Manchester, said: “Crocodile mummy 2005.335 was a unique opportunity to apply scientific analysis to a large animal mummy.

“Our work revealed a great amount of information, both about the life of the crocodile and the post-mortem treatment of it remains.

“Mummies have long been a source of fascination for museum visitors of all ages. Our work provides a unique opportunity to connect visitors to the story of this animal.”

She added: “Whereas earlier studies favoured invasive techniques such as unwrapping and autopsy, 3D radiography provides the ability to see inside without damaging these important and fascinating artefacts.

“We took take the process a step further by replicating the hook in its original material, bronze.

“The Egyptians probably used a hardened clay mould into which the molten metal, melted over a charcoal-based heat source, would have been poured.

“Despite the passing of several millennia between the production of the ancient fish hook and the modern replica, the casting process remains remarkably similar.”

Images :

• Crocodile in the CT scanner
• The reconstructed hook
• The skeleton with gastroliths in stomach, obscuring the hook
• Xray showing hook in the animal

The Consultant in Genomic Medicine, 91ֱ�� Centre for Genomic Medicine, Saint Mary’s is one of 58 exceptional biomedical and health scientists elected to the Academy’s Fellowship for 2024 – an endorsement of an individual's significant impact in their field.

Professor Newman, who is also Rare Conditions Co-Theme Lead at the National Institute for Health and Care Research (NIHR) 91ֱ�� Biomedical Research Centre (BRC), said: “I am honoured and delighted to receive this acknowledgment from the Academy of Medical Science.

“This award reflects the work and commitment of all the patients, researchers and clinicians that I have worked with, who have supported the many initiatives in which I have been privileged to lead.

“I look forward to joining the Fellowship of researchers, at the heart of the Academy's work, including nurturing the next generation of researchers and shaping research and health policy in the UK and worldwide.”

Through his work in pharmacogenetics which involves understanding why patients respond differently to their medication, he has also led innovative point of care genetic studies to prevent critically ill newborn babies, usually treated with a common antibiotic, from going deaf. This has resulted in a ground-breaking bedside test that is now being used in routine clinical practice in maternity settings at 91ֱ�� University NHS Foundation Trust (MFT) and will be rolled out at NHS trusts across Greater 91ֱ�� in the summer. This work has been supported by the NIHR 91ֱ�� BRC, hosted by MFT.

In addition to this, Bill’s national leadership roles include Chair of the British Society for Genetic Medicine and President Elect of the European Society of Human Genetics, having led the education committee for the past five years.

The new Fellows will be formally admitted to the Academy at a ceremony on Wednesday 18 September 2024.

The Academy of Medical Sciences is the independent, expert body representing the diversity of medical science in the UK. Its mission is to advance biomedical and health research and its translation into benefits for society. The Academy's elected Fellows are the most influential scientists in the UK and worldwide, drawn from the NHS, academia, industry and the public service.

The  findings of the University of Oxford led study, published in , are an exciting first step towards the development of future  treatments for the disorders which have devastating impacts on learning, behaviour, speech, and movement.

While most NDDs are thought to be genetic and caused by changes to DNA, to date around 60% of individuals with the conditions do not know the specific DNA change that causes their disorder.

Nearly all genes known to be involved in NDD are responsible for making proteins. However the team discovered that the gene RNU4-2 instead makes an RNA molecule that plays an important role in how other genes are processed in cells.

The study estimates that these specific changes in the RNU4-2 gene can explain 0.4% of all NDD cases globally, potentially impacting hundreds of thousands of families across the world.

While previous studies have only looked at genes that make proteins, data from the , used by the team meant they could sequence entire genomes enabling changes in genes that don’t make proteins, like RNU4-2, to be analysed as well.

The study was led by Nicola Whiffin, Associate Professor at the Big Data Institute and Centre for Human Genetics at the University of Oxford.

The team found mutations in RNU4-2 in 115 people with NDDs, many of whom had the exact same variant which adds a single extra base at an important position in the RNA.

The second haJamie Ellingford is  Senior Research Fellow at The University of Manchester and Lead Genomics Data Scientist at Genomics England

He said: “This is a really powerful discovery which shows just how far we have developed as a global scientific and clinical community.

“It provides evidence of how we now have the capability to pinpoint all types of differences in people's DNA which can be drivers of disease, and can rapidly connect families and researchers from across the world.

“The University of Manchester has an excellent track record at the cutting edge of human genomics research and the discovery of new types of diseases.

This finding builds upon jointly led work at the University of Manchester and the University of Oxford to understand the impact of DNA differences in the part of the human genome that doesn't directly encode for protein, once called "junk DNA" because of its unknown role.

“The close alliances between computational science, genomics and clinical discovery at The University of Manchester will hopefully enable future discoveries like this that help families and other researchers better understand genomic diseases."

Nicole Cedor, mother to 10-year-old Mia Joy, said: “When Undiagnosed Network told us about three years ago that there was nothing else they could do, we resigned ourselves to the fact that we may never find out.

“So, you can imagine our shock to get this news. With the information we have gained, we are getting blood work to check iron levels, getting a DEXA bone scan next week, and we have a referral in for endocrinology.”

“We are so grateful to each person on the research teams that worked tirelessly to find this diagnosis.  It is one thing to write papers and crunch all that data, then another to see a family with a precious unique child who is living it day by day.  This where the data meets real life. We like to refer to RNU4-2 as "renew", as our family is being renewed by this new information and hope for the future.”lf goes here.

Professor Whiffin said: “What is most remarkable about this discovery is how often changes in this gene result in NDD. Most protein-coding genes involved in NDD are thousands of DNA bases long. RNU4-2 is around 50 times smaller but changes in this gene are almost as frequent a cause of NDD as these protein-coding genes. Including RNU4-2 in standard clinical genetic testing will end diagnostic odysseys for thousands of NDD patients worldwide and provide long-awaited hope to families.”

The study, published in, challenges current scientific models which argue that by 2050, coral reef fish could shrink by 14-39 percent in size due to increasing temperatures under climate change.

The researchers from NYU Abu Dhabi, the Hawaii Institute of Marine Biology and The University of Manchester, identified how coral reef fish living in the Arabian Gulf - the warmest waters on earth - have adapted to survive extreme temperatures.

It was led by John Burt, co-principal Investigator at at NYU Abu Dhabi and Jacob Johansen, Associate Research  Professor at the  Hawaii Institute of Marine Biology.

Though they studied two kinds of fish the findings are likely to be relevant to other species.

Professor Holly Shiels was also on the team, along with her PhD students Dan Ripley and Grace Vaughan.

She said: “The Arabian/Persian Gulf is a window to future ocean conditions and working together with colleagues in the region we have used this natural laboratory to provide new insight into impact of rising water temperatures on fish.

“Our study offers hope for some marine species in a continuously warming world.”

According to the researchers, adaptations in both metabolism and swimming abilities helped the fish to survive extreme conditions in the Arabian Gulf.

The warming of our oceans is anticipated to drastically affect marine life and the fishing industry, potentially upsetting entire ecosystems and economic structures reliant on these habitats.

However, the study’s findings challenge the prevailing view that oxygen supply limitations in larger fishes are the main reason for smaller fish in warmer waters – known as the “shrinking fish phenomenon.”

The researchers instead argue the decrease in fish size and their survival in increasingly warm oceans might be more closely related to an imbalance between how much energy fish species can obtain and how much they need to sustain themselves.

The researchers compared two species of fish, the Blackspot snapper and the Arabian monocle bream, surviving under the elevated temperatures within the Arabian Gulf to those of similar age living in the cooler, more benign conditions in the nearby Gulf of Oman.

They determined the qualities reef fish in the Arabian Gulf have that enable them to survive there, where typical summer water temperatures are comparable to worst-case ocean warming projections for many tropical coral reefs globally by 2100.

John Burt said: “The hottest coral reefs in the world are an ideal natural laboratory to explore the future impact of rising water temperatures on fishes.

“Our findings indicate that some fish species are more resilient to climate change than previously understood and help explain why smaller individuals are evolutionarily favored at high temperatures.

This has significant implications for our understanding of the future of marine biodiversity in a continuously warming world.”

• “Causes and consequences of ocean warming on fish size reductions on the world’s hottest coral reefs” is published in the journal

The 91ֱ�� Hair Research Group team unexpectedly discovered the link in a lab experiment where they were testing a drug to see if it cultivates human scalp hair follicles in a dish.

The study inadvertently led to a link to the cellular stress response - an ancient biological mechanism which occurs across life from yeast and roundworms through to humans.

The team hope that by targeting the pathway, treatments for hair loss might one day be found.

Known in full as the Integrated Stress Response-  or ISR-  it is triggered in stressful cellular conditions such as poor nutrient availability, viral infection, or when there is a build-up of misshaped proteins in cells.

The ISR allows cells to put a brake on regular activities by making less new proteins, entering a partial stasis to adapt and deal with the stress. However, if it doesn’t work, it can cause cells to die.

ISR is already the subject of great interest to scientists studying cancer, neurodegenerative disorders and ageing.

The study is published in the peer-review open access journal PLOS ONE today (insert date).

Dr Talveen Purba, Research Fellow at The University of Manchester and senior author of the study said “We were testing a drug that targets metabolism in human hair follicles to influence how cells generate energy, which based on the work of others, we expected to stimulate stem cells.”

“However we found the opposite was true: hair growth was instead blocked, as cells, including stem cells, quickly stopped dividing.”

They also found signs that mitochondria, the power plants inside cells,  were dysfunctional, and there were disruptions in how cells communicate with each other.

Using a combination of experimental approaches to look more closely, they found signs that ISR activation was to blame.

Derek Pye, chief technician of the research group and co-author of the study said “When we look at hair follicles under the microscope, it’s striking how consistent the response is between hair follicles from different people.”

Following on from this early-stage research, the team are now looking to better understand the broader implications of the ISR in hair follicles, and look at its activity in people with hair loss conditions.

Dr Purba added: "We're incredibly hopeful as we believe the activation of this pathway could play an important biological role in restricting hair growth in people with hair loss conditions, meaning that targeting it could lead to new treatments”.

The research paper entitled “Activation of the integrated stress response in human hair follicles” is  available online in the journal PLOS ONE :

Image:    Side by side comparison of untreated (left) and stressed (right) hair follicles highlighting changes to mitochondrial distribution (red)

has been awarded an OBE for his services to public health, to epidemiology and to adult social care, particularly during Covid-19, has been awarded an OBE for his for services to the advancement of the science of radiation protection, Professor Paul Klapper has been awarded an OBE for services to viral diagnostic testing, and Professor Paul Howarth has been awarded a CBE for his significant contribution and service to the nuclear industry and to UK research and development (R&D).

The list celebrates individuals who have had an immeasurable impact on the lives of people across the country - such as by creating innovative solutions or driving real change in public life.

Ian Hall is a Professor of Mathematical Epidemiology and Statistics at The University of Manchester. He is a long-standing member of SPI-M (the pandemic disease modelling advisory group) and played a critical role in the operations of this group during the swine flu and Covid-19 pandemics.

During the Covid-19 pandemic he was academic chair of the SAGE working group of Social Care and participated in the SAGE Environmental Modelling Group as well as attending SAGE itself. He was also involved in a number of research projects, including the national core study on transmission () and Project TRACK to understand and control the risks on public transport. He also helped analyse data from a new heat map, providing a national picture of the spread over time.

Since the pandemic, Professor Hall has continued working with UKHSA through an honorary contract, notably with Health Equity Division on vaccination strategies in prison and homeless settings.

His other research interests include the impact of diseases on vulnerable populations and the study of vector-borne infectious diseases and environmental infections, such as Legionnaires Disease.

Richard Wakeford is an Honorary Professor in Epidemiology in the Centre for Occupational and Environmental Health (COEH), having been Professor in Epidemiology at the Centre before retiring at the end of 2019. He specialises in the epidemiology of exposure to ionising radiation, particularly as related to radiological protection.

Professor Wakeford is a member of various committees, including the UN Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. He was a member of the Scientific Advisory Group for Emergencies (SAGE) following the Fukushima nuclear accident in Japan, and for 25 years was Editor-in-Chief of the Journal of Radiological Protection.

Richard completed his PhD in high energy physics at the University of Liverpool in 1978 and worked for British Nuclear Fuels Ltd (BNFL) for nearly 30 years. It was the many challenges faced at BNFL where he developed his skills in radiation epidemiology and radiological protection. He was privileged to work with Sir Richard Doll during this time. After taking early retirement from BNFL, Richard joined the University, initially through an association with Dalton Nuclear Institute and then joining COEH.

Paul Klapper is Professor of Clinical Virology at The University of Manchester. He began his career in virology in 1976 working as a laboratory technician at Booth Hall Children’s Hospital. He completed his PhD while working at 91ֱ�� Royal Infirmary on the diagnosis of herpes simplex encephalitis - a topic he continued to work on for over 20 years and led to the development of a reliable molecular diagnostic test for the condition. He also helped establish independent quality assurance testing in the infancy of viral molecular diagnostic testing. 

Throughout his career, Professor Klapper has been at the forefront of several key developments of viral diagnostic testing. Notably, he worked with the Greater 91ֱ�� Hepatitis C testing strategy, developing community-based testing methods to aid control of the HCV pandemic. In 1981, he became an NHS Clinical Scientist, working in both 91ֱ�� and Leeds as a Consultant Clinical Scientist. Ten years later, in 1991 became a Fellow of the Royal College of Pathology. 

On retiring from the NHS in 2012, Professor Klapper joined The University of Manchester as a Professor of Clinical Virology.  Early in 2020, he volunteered to help with establishment of large scale Covid-19 testing and became the clinical lead for the Alderley Park testing facility. He also served as a Clinical Advisor for testing with the Department of Health.

 Professor Klapper continues to conduct vital research in blood-borne virus infection and in congenital human cytomegalovirus infection.

Paul Howarth is Professor of Nuclear Technology at The University of Manchester and Chief Executive of National Nuclear Laboratory. 

Professor Howarth has had a distinguished career working in and for the nuclear sector, building a reputation as one of the leading figures in the UK nuclear sector and around the global industry. After completing his degree in Physics and Astrophysics and PhD in Nuclear Physics, he started his career working on the European Fusion Programme. Early in his career he was awarded a prestigious Royal Society Fellowship to work in Japan on their nuclear programme. On returning to the UK he continued to work on nuclear fission leading the UK’s advanced reactor programme while working at British Nuclear Fuels, co-founding the at the University  and working closely with UK Government on building the case for new nuclear build.

Professor Howarth was appointed CEO for the National Nuclear Laboratory (NNL) in 2011 following its creation as a public corporation, having been instrumental in its establishment from British Nuclear Fuels Limited (BNFL). During his tenure as CEO, NNL has been transformed into a successful business and a true national laboratory, delivering profits to reinvest into nuclear science and technology and critical support to nuclear organisations in the public and private sectors. 

The birthday honours are awarded by the King following recommendations by the prime minister, senior government ministers, or members of the public.

The awards recognise active community champions, innovative social entrepreneurs, pioneering scientists, passionate health workers and dedicated volunteers who have made significant achievements in public life or committed themselves to serving and helping Britain.

To see the full Birthday Honours List 2024, visit: https://www.gov.uk/government/publications/the-kings-birthday-honours-list-2024  

Described by the ERC as among the EU’s most prestigious and competitive grants, today’s funding has been awarded to the following senior research leaders:

• , Professor of Emerging Optoelectronics, based in the and , to investigate scalable nanomanufacturing paradigms for emerging electronics (SNAP). The program aims to develop sustainable large-area electronics, a potential game-changer in emerging semiconductor markets, that will help reduce society's reliance on current polluting technologies while enabling radically new applications.
• , Chair in Evolutionary Biology, in the School of Biological Sciences, to investigate how genomic complexity shapes long-term bacterial evolution and adaptation.
• , in the Department of Physics and Astronomy, and Director of the Photon Science Institute to develop a table-top nuclear facility to produce cold actinide molecules that will enable novel searches for new physics beyond the standard model of particle physics.
• Professor Sir Andre Geim, who isolated graphene in 2004 with Professor Sir Konstantin Novoselov, to explore 2D materials and their van der Waals assemblies.
• , to lead work into chemically fuelled molecular ratchets. Ratcheting underpins the mechanisms of molecular machinery, gives chemical processes direction, and helps explain how chemistry becomes biology.
• , in the Department of Chemistry and  91ֱ�� Institute of Biotechnology, to develop enzymatic methods for peptide synthesis (EZYPEP). Peptides are fundamental in life and are widely used as therapeutic agents, vaccines, biomaterials and in many other applications. Currently peptides are produced by chemical synthesis, which is inefficient, expensive, difficult to scale-up and creates a huge amount of harmful waste that is damaging to the environment. EZYPEP will address this problem by developing enzymatic methods for the more sustainable, cleaner and scalable synthesis of peptides, including essential medicines to combat infectious diseases, cancer and diabetes.
•  , based in the Department of Physics and Astronomy, to explore Top and Higgs Couplings and extended Higgs Sectors with rare multi-Top multi-Higgs Events with the ATLAS detector at the LHC. This project aims at deeper insight into the most fundamental properties of nature beyond our current understanding.

The University of Manchester received seven of the 42 grants awarded to UK institutions.

The grant recipients will join a community of just 255 awarded ERC advanced grants, from a total of 1,829 submissions.

As a result of today’s announcement, the ERC will be investing nearly €652 million across the 255 projects.

Head of Department for Physics and Astronomy, which received three of the seven grants, said: “Today’s triple award reflects our department’s continued leadership in pioneering research. We’re home to Jodrell Bank, host of the Square Kilometre Array Observatory – set to be the largest radio telescope in the world; the National Graphene Institute – a world-leading centre for 2D material research with the largest clean rooms in European academia; we lead experiments at CERN and Fermilab; and – crucially – we host a world-leading community of vibrant and collaborative researchers like Professors Flanagan, Geim and Peters who lead the way. Today’s announcement recognises their role as outstanding research leaders who will drive the next generation to deliver transformative breakthroughs.”

, Vice-Dean for Research and Innovation in the Faculty of Science and Engineering at The University of Manchester, added: “Our University’s history of scientific and engineering research is internationally recognised but it does not constrain us. Instead, it’s the work of our researchers – like the seven leaders celebrated today – and what they decide to do next, that will define us.  We are proud to have a culture where responsible risk-taking is nurtured and transformative outcomes delivered, and we look forward to these colleagues using this environment to deliver world-leading and world-changing research.”

, Vice-Dean for Research and Innovation in the Faculty of Biology, Medicine and Health, said: "These awards are welcome recognition of the world-leading and transformative frontier science that The University of Manchester researchers are delivering. The compelling and innovative research supported by these ERC awards builds on the excellent local environment at 91ֱ�� and are cornerstones of the University’s strategy for excellence and leadership in research and innovation. The positive and real-world global impact from these research awards could deliver are genuinely tangible.

"As we enter our third century, the awards made in a highly competitive environment, are evidence that we do so with a continued pioneering approach to discovery and the pursuit of knowledge that our research community was built on."

Iliana Ivanova, Commissioner for Innovation, Research, Culture, Education and Youth at the ERC, said: “This investment nurtures the next generation of brilliant minds. I look forward to seeing the resulting breakthroughs and fresh advancements in the years ahead.”

The ERC grants are part of the EU’s Horizon Europe programme.

The bid was delivered by a coordination team, which includes and from the University and has secured £49.35m from the UKRI Infrastructure Fund to establish C-MASS - a national hub-and-spoke infrastructure designed to integrate and advance the country’s capability in mass spectrometry.

Mass spectrometry is a central analytical technique that quantifies and identifies molecules by measuring their mass and charge. It is used across science and medicine, for drug discovery, to screen all newborn babies for the presence of metabolic disorders, to monitor pollution and to tell us what compounds are in the tails of comets.

Researchers at The University of Manchester develop and apply mass spectrometry in many of its research centres and institutes, including the , the , , , the , and the

C-MASS will enable rapid methodological advances, by developing consensus protocols to allow population level screening of health markers and accelerated data access and sharing. It will bring together cutting-edge instrumentation at a range of laboratories connected by a coordinating central hub that will manage a central metadata catalogue. Together, this will provide unparalleled signposting of data and will be a critical measurement science resource for the UK.

The bid for the funding has been developed over the last 10 years and has included input and support from more than 40 higher education institutes, 35 industrial partners and numerous research institutes.

91ֱ�� is renowned for its expertise in mass spectrometry. J.J. Thomson, who was an alumnus of The University of Manchester, built the first mass spectrometer - originally called a parabola spectrograph - in 1912. Later, another alumnus, James Chadwick, commissioned the first commercial mass spectrometer, built by the 91ֱ�� firm Metropolitan Vickers, for use in the second world war to separate radioactive isotopes.

Now, many decades later, the University receives more funding in mass spectrometry than any other higher education institution in the UK and more mass spectrometers are made in the 91ֱ�� region than any other in Europe.

At the University, researchers across a range of disciplines including , , use mass spectrometry for wide range of world-leading research. Just some of those projects include: , improving the testing and diagnosis of womb cancer, improving our understanding of Huntington’s disease and rheumatic heart disease, diagnosing Parkinson’s disease and finding treatments for blindness.

The mass spectrometry laboratories at the University boast a range of industry-leading instrumentations, not just for staff and students, but also collaborating with many external companies. 

The evolution of solutions is creating new opportunities to transform patient care and personal health outcomes. From remote monitoring and wearables, to artificial intelligence and machine learning, digital technologies are enabling health data collection and analysis and offering new insights, diagnosis and therapies.

Here is an overview of the Citation Impact on Digital Health Top 25 Rankings. The complete list can be accessed in ’s article.

Research into digital health has grown massively nowadays, whereas the scale of growth in digital health research is remarkable. Based on Clarivate data, publications on digital health topics – which include everything from wearable devices and mobile apps to AI analytics, telemedicine and 3D printing of drugs – have risen nearly 70-fold between 2013 and 2022, from a mere 39 Web of Science-indexed papers to 2,641 – while UK researchers were involved in 20 per cent of all papers.

The statistics demonstrate that the University currently has 75 digital health papers in the Web of Science, 1582 citations, 32 per cent of papers in the top 10 per cent by citation, scoring 2.50 category normalised citation impact (CNCI). It showcases 91ֱ��’s consistent efforts to advance digital health research that benefits the public.

Previously, the immense volumes of medical data from numerous wearable devices or mobile phones might have overwhelmed even the most data-savvy researcher. However, artificial intelligence now enables researchers to effectively navigate such vast amounts of information without requiring advanced coding skills. Likewise, hospitals and health centres worldwide are sharing patient records in a manner that allows algorithms to detect trends, including identifying emerging pandemics at their onset.

Recent University of Manchester research, alongside Oxford University and Cancer Research UK used Artificial Intelligence to reveal a new form of aggressive prostate cancer which could revolutionise how the disease is diagnosed and treated in the future.

For more information:

The cutting-edge 131,000 sq ft new building, of which UK Biobank will occupy three floors, will include laboratory space and a latest-generation robotic freezer that stores and retrieves UK Biobank’s 20 million biological samples four times faster than before, revolutionising the pace of scientific discovery. It will increase UK Biobank’s capacity, speed and efficiency and is supported by a £127.6m award from the UK Research and Innovation (UKRI) Infrastructure Fund for the next phase of UK Biobank’s development².

UK Biobank will be located alongside fast-growth life science businesses working in diagnostics, genomics, biotech and precision medicine in the highly specialist purpose-built building, which includes specialist labs and features such as increased vibration resistance, piped gas distribution systems, enhanced cooling and ventilation systems, high security access and 100GB superfast connectivity. The new facility will be 100% electric and net zero carbon in construction and operation in its shared spaces - one of the first lab spaces in the UK to be so.

Professor Dame Ottoline Leyser DBE FRS, Chief Executive of UKRI, said: “UK Biobank is a unique resource, powering research and innovation in the biomedical sciences, creating jobs, and connecting pioneering organisations. UKRI is investing significantly in UK Biobanks’ future. Recent enhancements to UK Biobank, such as the addition of whole genome sequencing data of its half a million participants, are drawing even more scientists to the database, increasing its potential to improve public health. This new facility will help to drive research and innovation on disease prevention and treatment.” 

The Secretary of State was joined by senior representatives from UKRI, the University of Manchester, Bruntwood SciTech, and UK Biobank. To mark this celebration, the Secretary of State completed the planting of the ‘living wall’ hoarding for the site, which will be maintained throughout construction before becoming part of a 7m high, two-storey green wall³ wrapping around the building to act as a layer of insulation, increase biodiversity and improve air quality.

The Secretary of State for Science, Innovation and Technology, Michelle Donelan, said: “UK Biobank makes an unparalleled contribution to science across the whole world, by putting invaluable information at researchers’ fingertips. It is already unlocking insights with the potential to detect Parkinson’s sooner, and tackle heart disease. It is without question a jewel in the crown of UK science, and an envy of the world. UK Biobank’s new home at 91ֱ�� Science Park – supported with an accelerated £21 million from Government – will mean it has the state-of-the-art facilities it needs, to keep its place at the forefront of our understanding of human health.”

The campus is one of the UK’s most well-established life science and technology hubs, home to 150 startups, scaleups, and globally leading businesses, and is located within the heart of the Oxford Road Corridor innovation district - Europe’s largest clinical academic campus. Supported by the University of Manchester, the new building importantly puts UK Biobank near leading institutions operating across research, academia, business and the NHS. This will provide UK Biobank with new opportunities for collaboration between multi-disciplinary researchers and industry which will stimulate innovation, health impact and economic growth in the 91ֱ�� region and beyond.

Dr Kath Mackay, Chief Scientific Officer for Bruntwood SciTech, said: “The UK's ambition to be a global leader in life sciences is contingent on the success and continued growth of regional hubs like 91ֱ�� Science Park. The arrival of UK Biobank at the campus marks an exciting milestone in its evolution, further cementing its position as one of the UK’s primary locations for innovation, collaboration, and discovery, and where businesses can gain direct access to some of the world’s most pioneering research, and a fully integrated clinical and academic ecosystem."

Professor Dame Nancy Rothwell FRS FMedSci, President and Vice-Chancellor of the University of Manchester and member of UK Biobank’s Board, said: “91ֱ�� is home to a globally acclaimed science and technology base and I’m really excited for UK Biobank to join this bustling hub of terrific research organisations which work closely with the University of Manchester to push the boundaries of science.”

The new centre is due to open in 2026 and will house UK Biobank’s biological samples, laboratories, headquarters and around half of its 250 staff. It will dramatically increase the speed at which UK Biobank can supply samples to researchers, allow for the storage of more samples as UK Biobank expands, and be more environmentally efficient. With a new home to store more samples, and in 2023, UK Biobank can now embark on pilot projects which will provide unrivalled data on human health and disease, such as:

●&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����; Repeating the first measures taken at recruitment for every participant. This will gather incredibly useful information about how people’s minds and bodies change over middle and old age and how this is related to disease development. It will also provide an opportunity to collect new measures to enable research into healthy ageing.

●&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����; Investigating different types of dementia and cancer. In the UK 1 in 10 people over the age of 65 have dementia, and 1 in 2 people will develop some form of cancer during their lifetime. There are several types of dementia, and even more forms of cancer. With more data from UK Biobank participants on these diseases there can be more research into their potential causes and the development of targeted treatments.

●&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����;&�Բ�����; Trialling remote forms of assessment, such as apps and wearable technology. This will open up a new way of collecting detailed data on participants’ health, including objective measures of movement and sleep.

     Professor Sir Rory Collins FRS FMedSci, Principal Investigator and CEO of UK Biobank, said: “This new facility is an essential step forward in ensuring that researchers across the globe can more efficiently access our millions of samples to turn them into data which can be used to propel research and innovation. My huge thanks go to UKRI whose generous funds have made the development of this new facility possible.”

This ceremony is particularly timely as it coincides with two UK Biobank milestones: 10,000 peer-reviewed papers have been published using UK Biobank's data, and 80,000 participants have had full body image scans collected as part of our efforts to complete the world's largest of 100,000 volunteers.

“None of this could exist without our amazing participants who give up their time and energy to provide the scientific community with the ultimate toolbox for investigating human health. I offer my eternal thanks to those half a million altruistic people,” added Professor Collins.  

Photo credit:  UK Biobank/Tim Ainsworth 

Caption: Jessica Bowles, Director of Strategic Partnerships and Impact, Bruntwood SciTech, Secretary of State Michelle Donelan, Prof. Dame Nancy Rothwell, University of Manchester & UK Biobank Board member, John Busby, Chief Operating Officer, UK Biobank 

The in , published by Elsevier, mean microRNA-29s, a class of small RNAs, could benefit patients affected by large-area or deep wounds prone to dysfunctional scarring.

The findings offer hope for an eventual to solution to the global problem of non-healing wounds, thought to cost between £11.25 billion and  £16.5 billion per year.

, from the University’s Division of Cell Matrix Biology and Regenerative Medicine, was lead investigator of the study.

She said: “We had data showing microRNAs can regulate skin growth. However, microRNAs do not code for proteins, so it wasn’t clear how such small molecules can make changes to the skin. We therefore studied underlying mechanisms that could be targeted to improve wound healing in the skin.”

There is already good understanding of the molecular events during early wound healing stages of inflammation and tissue formation, showing microRNAs are important factors in healing and may regulate functions in skin repair. However, the mechanisms underlying tissue remodeling are unclear.

Scientists studying wound healing in mice with microRNA-29 switched off have suggested the release of microRNA-29 targets promote wound healing by regulating skin regeneration.

That is done by binding long RNAs -  molecules carrying instructions from our DNA to different parts of the cell to make proteins – which code for a structural protein of the skin called laminin C2 (LAMC2).

LAMC2 is a crucial part of the glue that holds our cells in place and helps maintain the integrity and structure of tissues throughout the body, restoring the normal skin structure.

In the 91ֱ�� study, the researchers found that wild type mice healed quite well, but the skin of transgenic mice devoid of microRNA-29 regenerated even better.

To understand the reasons, they conducted deep microscopic analysis of the transgenic wounds and observed deposition of Lamc2—usually found in one of the skin layers in wild mice—around blood vessels inside the wounds of microRNA-29–deficient transgenic mice.

The observation showed microRNA-29 may be inhibiting the expression of Lamc2, and deletion in the transgenic mice relieved the inhibition, resulting in faster wound healing. Importantly, in human wounds, the new areas of LAMC2 deposition was found in wound matrix around small blood vessels under regenerating wound.

Dr Kurinna said: “These processes are likely to be mediated by the removal of microRNA-29, which improves cell matrix adhesion - the way cells in our body stick to and interact with the network of proteins and other molecules that surrounds cells known as the extracellular matrix.

“Our results further suggest a link between LAMC2, improved creation of new blood vessels (angiogenesis), and re-epithelialization -   the body's way of closing a wound.

“We expected the removal of microRNA-29 would help outer layers of the skin to grow faster. But it was the deep matrix of the wound that actually showed an improvement, and that was tremendously exciting.”

The findings demonstrate the role of microRNA-29 in epidermal repair and suggest the release of microRNA-29 targets, particularly LAMC2, promotes wound healing.

That could mean the inhibition of microRNA-29 and/or overexpression of LAMC2 may be a new and effective strategy for improving wound healing.

Dr Kurinna added: “Our findings are of particular interest because they describe the mechanism which restores normal skin structure, rather than a wound closure by scar tissue. Any improvement of normal skin repair would therefore help many patients affected by large-area or deep wounds prone to dysfunctional scarring.”

Some of the leading thinkers on different sides of  the debate around the topic spoke to  staff and students last month.

The audience at the event, called Culture of care or culture of concern: let’s debate animal research, put questions to the  panellists and debated them with audience members .

On the panel was Wendy Jarrett CEO of Understanding Animal Research (UAR), Penny Hawkins Head of the Animals in Science Department, RSPCA Science and Policy Group and  Celean Camp from CEO of the Fund for the Replacement of Animals in Medical Experiments (FRAME).

The event kicked off with the signing of a public pledge to a culture of care at The University of Manchester’s animal research unit by its Director, Dr Maria Kamper.

The panel was also  chaired by Mike Addelman, communications lead for animal research at The University of Manchester. 

He said: “This event was conducted in the best possible way. Our panelists, leading thinkers in the field, were constructive in what they had to say, and  engaged a lively and appreciative audience. 

"We covered many of the hotly debated areas in animal research, including alternatives to animal research,  sentience,  and if institutions who work with animals are transparent  enough.

“Audience members told me they went home  feeling as though they had learned something -  and that they understood more of the issues. "

If you want to watch the video of the debate-  split into three sections -  just click on the links below. And if you want to know more about the University's openness agenda,  email animal.research@manchester.ac.uk

Though the study, published in Nature Communications today (14/11/23) was in mice, the scientists suggest there is a high probability human cartilage and intervertebral discs - which have very similar physiological properties -will respond in a comparable way.

It also helps to contextualise an observation posed 300 years ago by a Reverend Mr Wasse, rector of Aynho in Northamptonshire, to a Dr Mead, concerning the difference in the height of a human body, between morning and night.

In the letter published by the Royal Society, the Reverend cited his observations of soldiers discharged from the army for being too short, arguing we are over half an inch taller after a good night’s sleep.

Daily rhythms in mammalian behaviour and physiology are generated by a circadian system which tunes into environmental cues such as light and feeding.

Scientists have long known that misalignment between the central body clock in the brain and other organs which have their own body clock – can increase the risk of pathology and diseases such as  diabetes and cardiovascular disease.

However until now, very little was understood about the relationship between the clocks in joint cartilage – which has no nerve or blood supply – and the brain.

The project was funded by consecutive grants from the Medical Research Council and Versus Arthritis.

Professor Qing-Jun Meng, a senior author and body clock expert from The University of Manchester said: “Not only have we identified that misalignment between cartilage and intervertebral disc clocks and our central clock in the brain can occur through exercising at an inappropriate time, we have found the mechanism by which this happens and that skeletal clocks can resynchronise to daily patterns of physical activity.

“Our earlier work discovered internal body clocks in intervertebral discs and cartilage that dampen with ageing.  Importantly, healthy cartilage and intervertebral discs have no nerves and no blood supply, so until now it was not clear how their internal clocks synchronise with the brain.”

Professor Judith Hoyland, another senior author and spine/intervertebral disc expert from The University of Manchester said: “Among the many health challenges, the age-related musculoskeletal decline - and its adverse consequences -is a major burden to individuals.

“Loss of bone density, degraded articular cartilage and degeneration of the intervertebral discs are primary features of the ageing skeleton, all of which can contribute to pain and loss of mobility.

“Importantly, we have identified a new clock mechanism underlying skeletal ageing, which could have far-reaching impacts on understanding frailty and designing more efficient treatment timing of exercise and  physiotherapy to maintain good skeletal health and mobility.”

Dr Michal Dudek, lead author from The University of Manchester said: “While we are standing and moving around during the day, water is pressed out of intervertebral discs in our spine as well as the cartilage in hips and knees, making us slightly shorter by the end of the day – just as the Reverend Mr Wasse identified 300 years ago.

“But what he didn’t know was that this causes increase in osmolarity of the tissue because the same amount of minerals is now dissolved in less water so the actual concentration increases. Cells sense this change in osmolarity and synchronise the clocks within these skeletal tissues.”

“The water comes back at night when we rest and osmolarity decreases, though this direction of change had no effect on the clock.

The scientists examined the mice who were given daily exercise on a treadmill during their resting time to show what happened to the clocks in the cartilage, intervertebral disc and the brain.

They confirmed the findings by compressing mouse intervertebral discs or cartilage explants in the lab or exposing them to higher osmolarity culture medium within a normal physiological range. Both resulted in a similar clock synchronising effect.

Professor Qing-Jun Meng said: “We have in effect identified a new mechanism to understand how our body clocks align to the external environment.

“The clocks have evolved to prepare you for predictable rhythmic changes in the environment.

“Our results showed that physical activities in the morning, associated with daily patterns of sleep/wake cycle, convey timing information from the light-sensitive central clock in the brain to the weight bearing skeletal tissues.  In effect it’s telling your skeletal system it’s time to wake up.

“But when this alignment is uncoupled with the brain, then like in other organs and tissues it can result in adverse impacts on your physical health.

“If you are constantly changing the time you exercise, you may be more prone to this desynchronisation.

“However, if you change when you exercise, but then maintain that regime for some time, we show that your body clocks will eventually re-align with each other and you will adapt to it.”

He added: “So, for example,  frequently switching time zones to compete in sports events-  a facet of the life of the international athlete for example, may undermine athletic performance and could make individuals more prone to injury.

“And our work showed that clocks in skeletal tissues of older animals remain responsive to daily patterns of exercise.  As such,  walking groups organised for older people could be more beneficial for their health if they happen at a similar time every day.”

Lucy Donaldson, Director of Research & Health Intelligence at Versus Arthritis, said: "We already know that exercise is one of the best ways to reduce the pain and impact of arthritis, and this very early research shows that exercising at certain times of day might bring added benefits for people with arthritis.

"The daily 24-hour cycle that our bodies follow, such as our internal temperature dropping when we sleep and our blood pressure rising at certain times of day, is known as our circadian rhythm. There are processes inside our body which keep this rhythm going, known as 'clocks', which are all linked to our central body clock in the brain.

"This early research in mice explores a link between the local clocks in joint cartilage and the central body clock in the brain, which the results suggest contribute to how quickly our bones and cartilage deteriorate over time. The findings show that when these clocks go out of sync, our bones and cartilage deteriorate faster, but when they're aligned, the process is slowed down. Exercising at certain times of day helps to keep the clocks in sync and so could slow the progression of arthritis.

"This is an important discovery because it could help us to develop more targeted treatments for musculoskeletal conditions such as arthritis using exercise and physical activity."

 The DOI for this paperis 10.1038/s41467-023-42056-1 and  is available to view online

This list coincides with the publication of the Home Office’s report on the statistics of scientific procedures on living animals in Great Britain in 2022.

These ten organisations carried out 1,434,403 procedures, 52% or just over half of the 2,761,204 procedures carried out on animals for scientific research in Great Britain in 2022*. Of these 1,434,403 procedures, more than 99% were carried out on mice, fish and rats and 82% were classified as causing pain equivalent to, or less than, an injection.

The ten organisations are listed below alongside the total number of procedures they carried out in 2022. Each organisation’s name links to its animal research webpage, which includes more detailed statistics. Case studies explaining how animal research has been used in recent medical research are also provided in the Notes to Editors section. This is the eighth consecutive year that organisations have come together to publicise their collective statistics and examples of their research.

UAR has also produced a of 64 organisations in the UK that have publicly shared their 2022 animal research statistics. This includes organisations that carry out and/or fund animal research.

All organisations are committed to the ethical framework called the ‘3Rs’ of replacement, reduction and refinement. This means avoiding or replacing the use of animals where possible, minimising the number of animals used per experiment and optimising the experience of the animals to improve animal welfare. However, as institutions expand and conduct more research, the total number of animals used can rise even if fewer animals are used per study. 

All organisations listed are signatories to the , which commits them to being more open about the use of animals in scientific, medical and veterinary research in the UK. More than 125 organisations have signed the Concordat including UK universities, medical research charities, research funders, learned societies and commercial research organisations.

Wendy Jarrett, Chief Executive of Understanding Animal Research, which developed the Concordat on Openness, said:

“Animal research remains a small but vital part of the quest for new medicines, vaccines and treatments for humans and animals. Alternative methods are gradually being phased in, but, until we have sufficient reliable alternatives available, it is important that organisations that use animals in research maintain the public’s trust in them. By providing this level of information about the numbers of animals used, and the experience of those animals, as well as details of the medical breakthroughs that derive from this research, these Concordat signatories are helping the public to make up their own minds about how they feel about the use of animals in scientific research in Great Britain.” 

Dr Joanna Stanley, Named Training and Competency Officer and 3Rs manager at The Biological Services Facility, University of Manchester, said:

“At the University of Manchester, we ardently advocate for the 3Rs – Replacement, Reduction, and Refinement of animal usage in research. The 3Rs are ingrained in all aspects of our work, from striving to replace animals in research procedures whenever feasible, to implementing the most up-to-date refinements in our housing and husbandry practices. We are deeply committed to this approach, as it allows us to conduct the most pertinent and reproducible research while maintaining the highest standards of animal welfare.”

Professor Anne C Ferguson-Smith, Pro-Vice-Chancellor (Research & International Partnerships) and Arthur Balfour Professor of Genetics, University of Cambridge, said:

“In Cambridge we have careful monitoring of our animal usage, applying reduction, replacement and refinement of animal work to ensure that they are only used when there is no alternative. For example, animals are used in research tackling neurodegenerative diseases like Parkinson’s and Multiple Sclerosis, and in repairing damaged nerves to restore movement to paralysed limbs.

We want to make major improvements to people’s lives, and we have a moral responsibility to ensure new treatments or procedures are safe, by assessing them first on animals, before developing approaches to apply them to humans.”

Dimitrios Anastasiou, Senior Group Leader, and Chair of the Crick’s 3Rs Committee, said:

“We want to understand more about how living things work to help improve treatment, diagnosis, and prevention of human disease. The Crick research infrastructure offers easy access to a range of non-animal methodologies. However, animals are still needed to provide insights into how complex organisms work and what goes wrong in disease. If we use animals, we do so with the least number of animals, while ensuring the most optimal conditions to minimise the impact on animal welfare.”

Dr Catherine Martin, Vice-Principal Corporate Services, University of Edinburgh, said:

“The University of Edinburgh uses animals in research only when their use is justified on scientific, ethical and legal grounds and when no suitable alternatives are available. We demonstrate our commitment to the 3Rs – Replacement, Reduction and Refinement – in numerous ways, including the development and use of non-animal models, such as in vitro methods, computer modelling and human subjects, where appropriate. We will keep working on the implementation of these principles across the University of Edinburgh to address scientific challenges while continuing to strive to reduce the numbers of procedures carried out in animals.”

Professor Geraint Rees, UCL Vice-Provost (Research, Innovation & Global Engagement) said:

“Animal research forms a small but vital part of biomedical research at UCL, contributing to life-saving medical advances from cancer to dementia to Covid-19 and beyond. Our scientists use animals in their research only when necessary, while continually striving to develop new ways to replace animals in their research, reduce their usage, or refine their methods to mitigate harm, without detracting from the quality and potential impact of the research.”

Claire Newland, MRC Director of Policy, Ethics and Governance, said:

“The MRC, part of UKRI, supports the highest quality research that has led to the development of life-saving treatments and advanced our understanding of basic human biology. The use of animals has been necessary for many of these developments, including recent breakthroughs in our understanding of metabolism-associated diseases.

MRC-funded research has the highest possible level of animal welfare and is guided by the principles of replacing, refining and reducing the use of animals, MRC upholds the commitments of the recently published .”

Dr Julie Keeble, Interim Director of Biological Services at King’s College London, said:

“At King's we are committed to enabling world class research that puts animal welfare first. Research on animals is only carried out where there are no alternatives and where an integrated whole-body system is required to advance research.”

David Duncan, University of Glasgow Deputy Vice Chancellor and Chief Operating Officer, said:

“Research using animals makes a vital contribution to the understanding, treatment and cure of a range of major diseases and viruses in humans such as cancer, Alzheimer’s and COVID-19. While the University is committed to the development of alternative methods – such as computer modelling, tissue culture, cell and molecular biology, and research with human material – some work involving animals must continue for further advances in medical sciences to be made. Animals are used in research only where it is essential, and the University remains committed to the principles of reduction, refinement, and replacement. All research undertaken on animals is conducted under strict ethical and welfare guidelines, under licence by the Home Office.”

Professor Marina Botto, Director of Bioservices, Imperial College London, said:

“Imperial continues its commitment towards the 3Rs principles and openness around animal research. At Imperial animals are used only when there is no other viable alternative to understand human diseases and how they can be treated. Imperial is committed to the highest standards of animal welfare and this is reflected in our accreditation by AAALAC International, which promotes the humane treatment of animals in science.”

Case studies for each institution, including The University of Manchester,  are available

*The Home Office recorded 2,761,204 completed procedures in 2022, 1,434,403 (52%) of which were carried out at these ten organisations.

The scheme aims to improve understanding of how changes to molecular networks surrounding cells lead to tissue decline, with the potential to positively impact chronic diseases including cancer and fibrosis.

Scientists argue that discovery research has near limitless potential to transform our understanding of life, health and wellbeing and improve people’s lives.

Sometimes, however, researchers are faced with substantial practical, technological and methodological barriers which prevent the pursuit of exciting new discoveries in their field.

But by overcoming the barriers, researchers will be able to ask even more creative and boundary-defying questions.

Graham Lord, Vice-President and Dean of the Faculty of Biology, Medicine and Health at the University of Manchester, said: “Our success in this competition, one of only eight awards, is underpinned by the excellence in fundamental research at the University of Manchester. The Discovery Research Platform for Cell-Matrix Biology is built upon many years of discovery science at our institution and will accelerate the understanding of mechanisms that underpin tissue structure and lead to the development of new insights directly relevant to human health.”

As a third of body mass, extracellular matrix surrounds cells, defines tissue architecture, and provides instructive signals for diverse cellular processes. Altered matrix is a hallmark of almost all genetic and acquired disorders leading to debilitating tissue degeneration and fibrosis. However, there are key conceptual and technical barriers to understanding how altered matrix leads to tissue decline. By innovating and improving technologies, this Discovery Research Platform aims to overcome these barriers and develop strategies to reprogramme the matrix and prolong tissue health.

Professor Rachel Lennon, Director of the 91ֱ�� Cell-Matrix Centre, said: "We have a bold vision to reprogramme extracellular matrix and prevent tissue decline. This exciting award will enable us to overcome major barriers that currently prevent the study of matrix in both time and space. We will share new tools and resources, and we aim to attract, inspire and nurture matrix researchers from diverse backgrounds."

Discovery Research Platforms will bring together researchers, teams and networks of collaborators to develop new tools, knowledge and capabilities, with the hope of accelerating progress for the benefit of the wider global research community.

Breaking down barriers to discovery research also relies on researchers being able to work in creative environments which include a diverse range of people and perspectives. Discovery Research Platforms will seek to deliver a positive and inclusive research culture that provides conditions for researchers to conduct their best work.

Michael Dunn, Director of Discovery Research at Wellcome, said: "Discovery research is essential to advancing our ability to understand and improve health. But in addition to researchers’ bold and imaginative ideas, we know that new tools, methods, and capabilities are also needed to unlock new avenues of research that can disrupt and transform the research landscape globally."

The funding is part of Wellcome's pledge to spend £16 billion over the next ten years to help solve some of the world’s most urgent health challenges. This includes supporting discovery research to provide researchers with the time, freedom, and resources to take on challenging questions that improve understanding of life, health, and wellbeing.

Michael Dunn added: "As part of our commitment to fund curiosity-driven discovery research, we want to tackle some of the barriers and bottlenecks across fields which hold back progress and limit the ability of researchers to take on big, challenging questions. Discovery Research Platforms are a brand-new approach for Wellcome. By providing substantial support focused on specific research challenges, these environments have the potential to revolutionise fields and provide maximum possible benefit for researchers around the world. I am particularly excited that Discovery Research Platforms span such an exciting range of disciplines, showcasing our increasingly inclusive approach to funding.”

Wellcome plans to convene all eight Discovery Research Platforms over the next year to encourage collaboration and the exchange of best practice between researchers and teams working in these environments.

Discovery Research Platforms are a part of Wellcome’s long-standing and enthusiastic commitment to funding fundamental science that shapes the world around us.

Images:  

• Matrix Centre group photo
• Prof Rachel Lennon (director of the centre) and research fellow Richard Naylor
• Goup of researchers: Rachel, Richard, Maryline Fresquet, Nikki Koudis and Louise Hopkinson

Matthew Cobb, from The University of Manchester and  Nathaniel Comfort from the John Hopkins University School of Medicine make the case for the scientist in a comment article in this week’s .

The seminal paper by James Watson and Francis Crick on the discovery of the DNA double helix was published in Nature 70 years ago this week.

Many believe the eureka moment came when Watson was shown an X-ray image of DNA taken by Franklin, without her permission or knowledge.

Known as Photograph 51, the image is treated as “the philosopher’s stone of molecular biology”, write Cobb and Comfort. “It has become the emblem of both Franklin’s achievement and her mistreatment,” they explain.

n this version of events, Franklin is portrayed as a brilliant scientist, but one who was ultimately unable to decipher what her own data were telling her about DNA. She supposedly sat on the image for months without realizing its significance, only for Watson to understand it at a glance.

But when visiting Franklin’s archive at Churchill College in Cambridge, the authors found a hitherto unstudied draft news article — written by journalist Joan Bruce in consultation with Franklin and meant for publication in Time magazine — as well as an overlooked letter from one of Franklin’s colleagues to Crick.

Together, she documents show that Franklin did not fail to understand the structure of DNA. Cobb and Comfort argue that Franklin was “an equal member of a quartet who solved the double helix”. Along with Maurice Wilkins, she was “one half of the team that articulated the scientific question, took important early steps towards a solution, provided crucial data and verified the result”.

Getting Franklin’s story right is crucial, write Cobb and Comfort. “She was up against not just the routine sexism of the day, but also more subtle forms embedded in science — some of which are still present today.”

One highlight was the stall organised by The University of Manchester’s Biological Services Facility (BSF) – otherwise known as the animal research unit.

Over the course of two days, the BSF engaged with hundreds of people including schoolchildren, teachers, parents and the public, who were wowed by what was on show.

The youngsters tried their hands at building mouse cages and learning about the types of enrichment the unit provides, while their parents and teachers asked detailed questions about animal research and the type of studies the BSF carries out.

Visitors got to try their hand at a ‘match the animal with the research’ mini game, guessing which species of animal help scientists understand and develop treatments for different diseases, including cancer, diabetes and stroke.

In another interactive game they learned that mice were the most commonly used species in research.

They also tried out the virtual tour of the unit, available on the University website and learned what an embryonic Zebrafish looks like under the microscope

British Science Week is coordinated by the British Science Association and is funded by UK Research & Innovation (UKRI).

It is a ten-day celebration of thousands of events running throughout the whole of the UK with the aim of celebrating science, technology, engineering, and maths.

The organisers aim to make science relevant to everyone and help them discover their own connections with a series of inspiring activities, events and content.

Zach Bowden Communications, Data and Quality Assurance Officer at the BSF said: “British Science Week was a brilliant experience and a vital opportunity for us to engage with the public about Animal Research.

“Our aim was to highlight our proud record on animal welfare and the contribution animals make to scientific research.

“The mini games were particularly popular and our visitors were really fascinated to learn about the types of research carried out and why.

“We’re certain we changed the viewpoints of many groups  with our ‘Which animals are used most in research game’.

“Many people still thought rats and monkeys were common species used by scientists, but we were able to change that and explain how we now focus on alternative species such as Zebrafish.”

Rachael Bowden, a Deputy Manager in the unit said: “It was really lovely to see so many people both school children and the public - actively engaging with discussions on animals in research and the technician’s role in this industry.”

Also on the team was Deputy Manager Natasha Allen. She said: “I did not anticipate the amount of engagement we would receive from the public, so it was a very positive experience.

“Kids of all ages got really stuck into the activities, and they asked a lot of questions. People left our stand feeling more informed, and I really enjoyed the openness of it all.”

"Alport syndrome affects around 1 in 5,000 individuals and is caused by alterations in collagen genes leading to kidney failure, hearing loss, and eye problems,” said , Pediatric Nephrologist and Director of the Wellcome Centre for Cell-Matrix Research at the University of Manchester.

Though there are treatments that can slow the progression of the kidney disease, there are currently no therapies that address the root cause of Alport syndrome, genetic variants that disrupt the genes encoding collagen IV, which is found throughout the body in a protein meshwork called the basement membrane.

"Fixing collagen in the kidney basement membrane is exciting, as this should also open new therapies for basement membrane-associated pathologies in other organ systems, such as in blood vessels, muscles, eyes, and ears.” , Jerry G. and Patricia Crawford Hubbard Professor of Biology at Duke University.

, Director of Scientific Collaborations, Duke University Liaison to Four Points Innovation said: "This project has great potential and illustrates the unique opportunity presented by this funding mechanism. It’s seizing on the strengths of the research coming from both Duke and The University of Manchester and catalyzing a milestone-driven research plan. In the absence of this arrangement with Deerfield, it is difficult to envision that this project would have gotten off the ground through more customary funding vehicles."

Through Four Points Innovation, Deerfield has committed up to $130 million of funding for 10 years for Duke-affiliated preclinical development of new drugs for improved quality of life and cures for disease.

"We are excited to launch our first project with Four Points and begin our collaborative work to translate this novel therapy into a potential treatment" said Michael Foley, PhD, CEO, Deerfield Discovery and Development at Deerfield.

Researchers are looking for over-50s who have a family history of neurodegenerative conditions.

Studies have linked indoor and outdoor air pollutants to various health problems, including increased risk of cardiac and lung diseases, and changes to brain health - including a strong association between air pollution and dementia onset.

Funded by the Natural Environment Research Council (NERC), the Hazard Identification Platform to Assess the Health Impacts from Indoor and Outdoor Air Pollutant Exposures through Mechanistic Toxicology (HIPTox) project unites researchers from the Universities of Birmingham and 91ֱ�� with medics from NHS 91ֱ�� Foundation Trust.

The team will examine the impact on the human body of pollutants such as diesel exhaust, cleaning products, and cooking emissions. 

Project co-investigator Thomas Faherty, a research Fellow at the University of Birmingham, commented: “We're excited to launch the HIPTox programme – it’s an ambitious project and the largest of its kind. The study results will help us to better understand the most toxic common pollutants and further explore the link between air quality and dementia”.

Project co-investigator Jacky Smith, a professor at the University of Manchester, commented: “A key part of the study involves investigating potential genetic risk factors, which is why we are recruiting participants who have had a family member diagnosed with a neurodegenerative disorder, such as dementia, to determine if they are at higher risk of cognitive decline from air pollution.” 

Project lead Gordon McFiggans, a professor at the University of Manchester, commented: “Using the 91ֱ�� Aerosol Chamber facility, we can safely control exposure to several common air pollutants. Volunteers will attend the 91ֱ�� Clinical Research Facility, on Grafton Street, before and after the pollutant exposures to measure cognitive and physiological functions.”

Further information can be found by:

• visiting ;
• emailing cough.research@manchester.ac.uk; or
• calling 0161 297 9292.

The study was funded by Orchard Therapeutics, sponsored by The University of Manchester and conducted at 91ֱ�� University NHS Foundation Trust.

It found four out of five patients diagnosed with Sanfilippo have continued to gain cognitive skills in line with development in healthy children after being given the investigational gene therapy, OTL-201.

However, the researchers urge caution as the majority of patients have not reached the age of 4-5 years where the most severe stages of disease progression typically present.

The trial patients were 6 to 24 months of age at the time of administration of OTL-201, and the preliminary results are based on a median follow-up of 2 years (range: 9-30 months).

Patients enrolled in the trial will be followed for a minimum of 36 months during which time the study investigators will continue to report additional biochemical and clinical outcomes.

The rare genetic metabolism disorder called Sanfilippo syndrome Type A- or Mucopolysaccharidosis Type IIIA (MPS-IIIA)- is a genetic disease with devastating effects on the central nervous system affecting around 1 in 70,000 children.

Patients with MPS-IIIA have a mutation in the SGSH gene, causing them to lack an enzyme which normally breaks down large sugar molecules.

These molecules then accumulate in the cells of the body causing irreparable damage to many organs including the brain, leading to inflammation and damage to brain tissue.

The investigational gene therapy OTL-201 works by collecting a patient’s own blood stem cells and inserting a working copy of the SGSH gene using a modified virus, known as a lentiviral vector.

The patient’s modified blood stem cells, now including a working copy of the SGSH gene, are then given back to the patient.

This enables patients to then make this missing SGSH enzyme and provide it throughout the body from blood cells made in the bone marrow. These stem cells can make monocytes, which are specialised blood cells able to enter the brain. This means they can release SGSH enzyme to potentially help stop damage to the brain.

The results showed:

• An improvement in neurocognitive assessments compared with natural progression of the disease in one of the children at 18-months post-treatment.
• Three additional patients are currently within the normal cognitive development range at 9 to 18 months post-treatment, but require longer follow-up to assess outcomes.
• After a median of two years, OTL-201 which was generally well tolerated in all the patients, achieved sustained engraftment in the bone marrow.
• Higher amounts of the SGSH enzyme were seen than would be normally found in the blood and cerebrospinal fluid of healthy children.

Six serious adverse events (SAEs) have been reported in patients in the study and were considered to be caused by procedures required for the administration of OTL-201 or background disease. No SAEs were considered related to OTL-201 and no fatal cases have been reported, to date.

Professor Brian Bigger, Chair in Cell and Gene Therapy at the University of Manchester, who carried out the preclinical work said: “We have been hopeful this therapy will be transformative for patients- and these early results are very encouraging - but there’s still a long way to go.”

“Importantly, the safety profile of the investigational therapy is currently considered favourable in these patients, with the lentiviral vector reporting a polyclonal pattern of integration, and blood stem cells engrafting and producing cells in the blood system which are able to make the missing enzyme in patients.

“The human monocyte-specific promoter in the lentiviral vector was designed to have a very low risk of causing insertional mutagenesis - the accidental switching on of genes causing cancer. This is critical for the future safety of the patients and the developmental potential of this therapy.”

Professor Robert Wynn, Chief Investigator on the trial at The Royal 91ֱ�� Children’s Hospital, part of Manchester University NHS Foundation Trust (MFT) said: “These are encouraging results for children living with MPS-IIIA and their families, who currently have no effective treatment options.”

“In addition to sustained engraftment of gene-corrected cells and supraphysiological SGSH enzyme levels in the periphery, the early neurocognitive findings show most patients are gaining skills in line with the development of healthy children. In one patient, we also have seen a marked improvement from disease natural history, and we hope to see similar results in the other patients with longer follow-up.”

Professor Simon Jones, Consultant in Paediatric Inherited Metabolic Disease at the 91ֱ�� Centre for Genomic Medicine at Saint Mary’s Hospital and Clinical Director of NIHR 91ֱ�� Clinical Research Facility at Royal 91ֱ�� Children’s Hospital, said: “There are currently no other treatment options for children with MPS-IIIA. We hope this therapy will have a positive impact on the lives of our children and their families, improving the symptoms of this devastating disease.’

Leslie Meltzer, Ph.D., chief medical officer of Orchard Therapeutics said: “These promising early findings continue to show the ability of our HSC gene therapy platform to enable the migration of gene-corrected cells into the central nervous system and the localized delivery of therapeutic enzymes and proteins to the brain to potentially correct neurodegeneration in multiple severe conditions, building on our programs in neurometabolic disorders.”

“While these early results are encouraging, longer follow up is needed, as the majority of the patients in this trial have not reached the age where the most severe stages of disease progression typically manifest. We are working with our collaborators at The University of Manchester and Royal 91ֱ�� Children’s Hospital to continue following patients in this ongoing study and more fully characterize the clinical and safety profile of OTL-201.”

The results were presented at the WORLD ™2023 on Lysosomal Diseases on 24/02/23.

The paper, published in Nature today (22/02/23) makes significant advances in our understanding of how animals sense and respond to magnetic fields in their environment.

This new knowledge could also enable the development of novel measurement tools where the activity of biological cells - including potentially those in humans - can be selectively stimulated using magnetic fields.

The team show for the first time that a molecule present in all living cells called Flavin Adenine Dinucleotide (or FAD for short), can, at high enough amounts, impart magnetic sensitivity on a biological system.

Scientists already know that species such as the monarch butterfly, pigeon, turtle and other animals use the earth’s magnetic field to navigate over long distances.

But the discovery could mean the biological molecules required to sense magnetic fields are present- to a greater or lesser extent-  in all living things.

The study was funded by the Biotechnology and Biological Sciences Research Council.

Co-lead researcher and neuroscientist Professor Richard Baines from The University of Manchester said: “How we sense the external world, from vision, hearing through to touch taste and smell, are well understood.

“But by contrast, which animals can sense and how they respond to a magnetic field remains unknown.

“This study has made significant advances in understanding how animals sense and respond to external magnetic fields - a very active and disputed field.”

To do so, the research team exploited the fruit fly (Drosophila melanogaster) to manipulate gene expression to test out their ideas.

The fruit fly, although very different on the outside, contains a nervous system that works exactly the same way as ours and has been used in countless studies as a model to understand human biology.

Magnetoreception - as the sixth sense is called - is much more difficult to detect than the more familiar five-senses of vision, smell, hearing, touch and taste.

And that, says co-lead researcher and neuroscientist Dr Adam Bradlaugh from The University of Manchester, is because a magnetic field carries very little energy, unlike photons of light or sound waves used by the other senses which, by comparison, pack a big punch.

To get around this, nature has exploited quantum physics and Cryptochrome – a light-sensitive protein found in animals and plants.

Dr Alex Jones, a quantum chemist, from the National Physical Laboratory and also part of the team said: “The absorption of light by the Cryptochrome results in movement of an electron within the protein which, due to quantum physics, can generate an active form of Cryptochrome that occupies one of two states.

“The presence of a magnetic field impacts the relative populations of the two states, which in turn influences the ‘active-lifetime of this protein.”

Dr Bradlaugh said: ”One of our most striking findings, and one that is at odds with current understanding, is that cells continue to ‘sense’ magnetic fields when only a very small fragment of Cryptochrome is present.

“That shows cells can, at least in a laboratory, sense magnetic fields through other ways.”

He added: “We identify a possible ‘other way’ by showing that a basic molecule, present in all cells can, at high enough amounts, impart magnetic sensitivity without any part of Cryptochromes being present’.

“This molecule - Flavin Adenine Dinucleotide (or FAD for short) – is the light sensor that normally binds to Cryptochromes to support magnetosensitivity.”

The findings, say the researchers, are important because understanding the molecular machinery that allows a cell to sense a magnetic field provides us with better ability to appreciate how environmental factors (for example, electromagnetic noise from telecommunications) may impact on animals that rely on a magnetic sense to survive.

The magnetic field effects on FAD in the absence of Cryptochrome also provide a clue as to the evolutionary origins of magnetoreception, in that it seems likely that Cryptochrome has evolved to utilize magnetic field effects on this ubiquitous and biologically ancient metabolite.

Co-lead author Professor Ezio Rosato from The University of Leicester said: “This study may ultimately allow us to better appreciate the effects that magnetic field exposure might potentially have on humans.

“Moreover, because FAD and other components of these molecular machines are found in many cells, this new understanding may open new avenues of research into using magnetic fields to manipulate the activation of target genes

“That is considered a holy-grail as an experimental tool and possibly eventually for clinical use.”

The  paper ‘Essential elements of radical pair magnetosensitivity in Drosophila’ is available here

Photo credit: Anna Munro

The development of the method called ClinCirc could one day help doctors to target patients at risk of long term health problems caused by clock disruption, which is thought to be common in patients admitted to hospital.

With the help of ClinCirc, the study concluded that body clock disruption is common in patients:

• Reduced blood clock oscillations were observed in half of intensive care patients. This was associated with high levels of inflammation.
• The body clock was shifted, like jet lag, in nearly all kidney transplant patients immediately after their operation.

The body clock is known to regulate how animals respond to infection and whether they develop disease, but until now it has been difficult to measure in patients. Shift work or jet lag is likely to break the clock, a potential explanation for why these activities are linked to diseases, including obesity and diabetes.

The test devised by the team measures blood clock dysfunction in patients. This clock was altered in nearly all kidney transplant recipients (22 patients) and half of patients (13 patients) admitted to critical care.

The team, which includes researchers from Exeter University and 91ֱ�� University NHS foundation Trust, say that it is too early to tell the medical implications of their results, however, researchers can now explore medical hypothesis involving clock dysfunction because they can tell the body clock time accurately.

ClinCirc, which involves a series of blood tests over 24 to 48 hours, is described in a paper published in the Journal of Clinical Investigation today (20/12/22)

ClinCirc combines two existing mathematical methods: the Lomb-Scargle periodogram and cosinor analysis to determine whether specific genes follow a regular cycle of increase and decrease over 24-hours.

The investigators then used the technique to measure molecular oscillator “the body clock” in blood. This molecular oscillator is a core mechanism which drives many of the body clock outputs. 

The method was used to measure the body clock in 13 intensive care unit patients at 91ֱ�� Royal Infirmary and Wythenshawe hospital, some of whom had inflammation.

It was also used to measure the body clock in 22 Kidney transplant patients, receiving anti-inflammatory drugs immediately after the operation.

The study was funded by the Medical Research Council, National Institute of Academic Anaesthesia, Asthma and lung UK, the Engineering and Physical Sciences Research Council and Kidneys for Life organisation.

Dr John Blaikley from The University of Manchester and senior author on the study said: “We have proved that ClinCirc is a robust method which can enable us to characterise the patient’s body clock from blood samples.

“Using this system, we show that for many patients admitted to hospital their body clock may be altered by disease or the treatment they receive.”

Peter Cunningham and Gareth Kitchen both from The University of Manchester who performed the analysis of blood samples said “Other people have already shown that various hospital outcomes are affected by when they occur, therefore it will be interesting to see if this is linked by the alterations in the body clock described in this study”

Professor Andrew Hazel, a mathematician based at The University of Manchester, developed and configured the ClinCirc mathematical method working with Callum Jackson, a PhD student.

He said: “One of the great strengths of mathematics is that techniques originally developed for one application, in this case analysis of irregularly spaced astrophysical data, can be adapted to make progress in completely different areas of science.” 

The paper ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients is available here

Image by from

91ֱ�� researchers, based at Saint Mary’s Hospital, part of Manchester University NHS Foundation Trust (MFT), worked with The University of Manchester and 91ֱ��-based firm genedrive Plc on the Pharmacogenetics to Avoid Loss of Hearing (PALOH) study. Together, they developed the pioneering, rapid bedside genetic test which was .

Using a cheek swab, the test can identify in 26 minutes whether a critically ill baby admitted to intensive care has a gene change that could result in permanent hearing loss if they are treated with a common emergency antibiotic, Gentamicin.

While Gentamicin is used to safely treat approximately 100,000 babies a year, one in 500 babies carry the gene change that can lead to permanent hearing loss when given the antibiotic.

The new test means that babies found to have the genetic variant can be given an alternative antibiotic within the ‘golden hour’ and could save the hearing of 200 babies in England every year.

PALOH study lead, Professor Bill Newman, Consultant in Genomic Medicine at MFT and Professor of Translational Genomic Medicine at The University of Manchester, said: “I am delighted for the team to receive this recognition of their fantastic efforts and their innovative approach in bringing this test to fruition.”

The new swab test technique, which was piloted at MFT, replaces a test that traditionally took several days and is the first use of a rapid point of care genetic test in acute neonatal care.

Dr Ajit Mahaveer, Consultant Neonatologist, Rachel James, Senior Research Coordinator and Nicola Booth, Research Nurse Manager on the Newborn Intensive Care Unit at Saint Mary’s Hospital, attended the awards ceremony in London and accepted the award on behalf of the team.

Dr Mahaveer said: "I am incredibly proud to be part of the team who made this study a reality and to be recognised at this year’s New Statesman Positive Impact Awards. It’s an honour to accept the award on behalf of the team, knowing the work we have put into delivering this research will truly make a difference to hundreds of babies’ lives each year.

“As a doctor dealing daily with infection, my main concern was how easy and quickly the test was to conduct, as it’s important that we do not delay antibiotic treatment. Our experience of using this test has been very positive. It’s straight-forward, non-invasive and will have a huge impact on our patients’ lives.”

Professor Newman, Theme Co-Lead Lead for Rare Conditions, National Institute for Health and Care Research, 91ֱ�� Biomedical Research Centre, continued: “I am absolutely thrilled with the success of the study and that this test is now being used in routine clinical practice. This test will make a real difference, helping to ensure babies are not going to lose their hearing for a preventable reason.”

It is expected the test could save the NHS £5 million every year by reducing the need for other interventions, such as cochlear implants.

Professor Dame Sue Hill, Chief Scientific Officer for England and Senior Responsible Officer for Genomics in the NHS said: “This ground-breaking bedside test for detecting whether an antibiotic could cause deafness in babies in intensive care is another example of how the NHS is harnessing the power of genomic medicine to transform patient care. This award is a tribute to the hard work of Professor Bill Newman and his team in 91ֱ��.”

Dr Gino Miele, R&D Director, genedrive plc, said: “The collaboration of our company with the research and clinical team at MFT is a shining example of the NHS working with a commercial company to deliver real improvements in patient outcomes in a cost-effective way.”

Caption: Rachel James, Senior Research Coordinator; Nicola Booth, Research Nurse Manager, Newborn Intensive Care Unit and Dr Ajit Mahaveer, Consultant Neonatologist at Saint Mary’s Hospital, part of MFT receiving the award on behalf of the PALOH team. (Photo credit: New Statesman Positive Impact Awards)

Animal research communications lead Mike Addelman and Communication officer at the University’s animal unit Zach Bowden received the award from renowned cardiovascular researcher Professor Cherry Wainwright at a ceremony in London.

The judging committee were wowed by this year’s openness campaign, which used social media platforms to promote a YouTube video depicting a day in the life of an animal technologist featuring the University’s Rachael Bowden.

The campaign also promoted three case studies   penned by science writer Richard Berks - on the University’s pioneering 3Rs work on reducing animals numbers, finding ways to replace them, and refine projects to maximise animal welfare.

It is the second time 91ֱ�� have won the award - organised by (UAR); the University received recognition -  and widespread praise - for its pioneering website in 2016.

The website contains case studies, minutes, project non-technical summaries governance information and facts and figures, and a virtual tour of the unit.

UAR is a not-for-profit organisation which promote the broad understanding of the humane use of animals in medical, veterinary, scientific and environmental research in the UK.

They manage the Concordat on Openness on Animal Research, a set of commitments for UK-based life science organisations to enhance their animal research communications.

Launched by UAR in 2014, the Concordat currently has 128 signatories including the University. 91ֱ�� was one of 12 to be designated Leader in Openness status in 2019, which was renewed this year.

Maria Kamper, Director of the animal unit said: “Transparency has always been a cornerstone of our work. This stems from our strong conviction to support ground-breaking research  at 91ֱ�� and the high standards of animal welfare we foster.”

Animal research communications lead Mike Addelman said: “This award is the culmination of many years of work- in which we have transformed The University of Manchester into one of the most open institutions in the UK -  and beyond in animal research.”

Zach Bowden, communications officer for the University of Manchester animal unit said: “We are very proud of this achievement, and look forward to continuing our work on openness in the coming year through some new and exciting projects.”

The former chair of the Spine Section for  the American Orthopaedic Research Society started her research career in in 91ֱ�� in 1985, received the award for her research in on molecular mechanisms underlying disc generation.

She has published over 190 papers  in the area of musculoskeletal tissue cell and molecular biology and pathology.

She has internationally renowned expertise in the cell biology of musculoskeletal tissues, particularly intervertebral disc  and its degeneration and more recently tissue engineering and cell-based regeneration of the  intervertebral disc .

The PSRS Lifetime Research Achievement Award was created in 2013 to honour an investigator who has established him or herself with sustained and long-lasting contributions in the area of spine research.

The award is given biennially when at the Orthopaedic research society PSRS International Research Symposium.

Past recipients include  Professor Irving Shapiro, the Anthony and Gertrude DePalma Professor of Orthopaedic Surgery and Director of Orthopaedic Research at Thomas Jefferson University, Professor Peter Roughley, Shriners Hospital for Children, Montreal, Jill Urban, PhD, Senior Research fellow Emeritus in the Department of Physiology, Anatomy and Genetics Oxford University and Professor Michele Battie, University of Alberta.

The Lifetime Achievement Award carries an honorarium of $1,000 and a commemorative plaque. The formal presentation of the award will take place during the PSRS 6th International Spine Research Symposium, November 6-10, in, Pennsylvania.

Professor Hoyland said: “I am truly honoured to receive this prestigious award from the ORS PSRS and thank those who nominated me. I am very grateful for the recognition I have received for my research work  into the biology of the intervertebral disc and the pathogenesis of disc degeneration - a major cause of low back pain.

“Of course, it isn’t just me that has achieved this but the team of researchers I have worked with and the infrastructure provided at The University of Manchester that has enabled me to progress research in this area over the last 20 or so years  to  make a  substantial impact in the field and thus I would like to say a  huge thank you to all those I have worked with.”

The study of mice and published in Current Biology is also the first to show that the well-established protective effects of fasting are at least in part mediated by the brain, rather than a lack of nutrients as generally thought.

Funded by the Medical Research Council, the scientific team show that tricking the brain into thinking it is fasting is sufficient to induce effects of real fasting in otherwise well-fed mice.

Scientist have long known that periodic fasting can help promote a range of health benefits including reducing the severity of chronic inflammation, immune system regeneration, alleviating side effects of chemotherapy and even promote longevity.

But the researchers now show it is possible to induce some of the beneficial effects of fasting in mice, without them actually fasting.

The team developed a way to switch on a group of about 5,000 specialist brain cells called AgRP neurons  -a tiny figure compared to the 70 million or so nerve cells in the whole brain   which are responsible for generating the feeling of hunger.

Using specialist imaging techniques they were able to visualise the effect of a systemic inflammation in the mice who’s specialist brain cells had been engineered to glow fluorescently.

Loss of appetite and negative energy balance are common features of infection and inflammation in all animals, but are thought to have protective roles by reducing nutrient availability to host and pathogen metabolism.

However, the team discovered that the AgRP neurons detect reduced level of nutrients and respond by sending back to the body signals which have anti-inflammatory effects. Artificially turning on these specialist brain cells was also sufficient to generate anti-inflammatory effects.

Senior of author Dr Giuseppe D’ Agostino from The University of Manchester said: “Though it can be seen as paradoxical, the beneficial effects of fasting during sickness are well known”.

“We have now discovered that the brain plays an important role in this mechanism.”

Dr Gabriella Aviello from the University of Naples added: “There is obviously a long way to go, but the hope is that if we can exploit this mechanism, there could be a way to develop fasting memetic therapies which generate the beneficial effects of fasting, in those medical conditions where calorie restrictions is less desirable or counterproductive.”

The paper Hypothalamic AgRP neurons exert top-down control on systemic TNF-α release during endotoxemia is available

In the study, published in , 26 people were shown pictures of objects that were either natural, such as fruit, tress, flowers,  or man-made such as a computer mouse and telephone.

In the study funded by the Wellcome Trust, the scientists trained the participants to expect man-made or natural objects using cues such as a triangle or a square.

The whole experiment was then repeated with another 24 people having a functional MRI scan to reveal which regions of the brain were used to learn and retrieve the information.

When an expected event – such as a triangle preceding a man-made object  - followed a similar but unexpected event – a triangle preceding a natural object – the participants’ memory was boosted.

The second study in the MRI scanner gave exactly the same behavioural results, and showed activation in the brain’s hippocampus – the memory centre , midbrain regions – which release dopamine, and occipital cortex - the vision centre.

In contrast, a sequence of two unexpected similar events also triggered visual areas in the brain, but did not enhance memory performance.

Lead author Dr Darya Frank, a cognitive neuroscientist from The University of Manchester, said: “We already know that if expectation is violated before or during learning, it triggers an adaptive mechanism resulting in better memory for unexpected events.

“This experiment shows how the mechanism is also affected when we are trying to retrieve information.”

The hippocampus encodes  - or creates -  memories but also  retrieves memories. With only a finite amount of resource to allocate to either, the two mechanisms  are in conflict.

So when something unexpected happens, our brain focuses on the outside environment so it can learn something new, something it did not initially expect.

Scientists already know that surprise turns on the brain’s learning mode, add link however, the current study is the first to investigate how the brain uses the mechanism when we are trying to retrieve information.

Dr Frank added: “Though our study did not assess the impact of these findings on exam revision and performance, it is logical to see its implications.

“So when the goal is to retrieve information -  encountering surprising events like revising in a café or other unfamiliar surroundings would engage an encoding mechanism that may enhance memory for a future exam.

“But the reverse is also true: when trying to remember something already learned during the exam itself, a familiar and expected environment could be helpful, and support retrieving information from memory.

The discovery published in Current Biology shows that the fruit trees, which develop rubbery branches when infected, mirrors how scientists are trying to  genetically modify trees.

Apple rubbery wood virus (ARWV) -which causes apply rubbery wood disease - is now largely, if not totally, eliminated from commercial apple trees.

However, an extensive survey in the UK during the 1950s when ARWV was widespread revealed that in some cases, over 50% of apple trees sampled were infected with the virus

The widespread  presence of the virus  across the globe is well documented.

Though their branches become more flexible, no adverse effects to humans who have eaten fruit from the infected trees have been recorded and there have been no adverse environmental consequences..

Funded by the , the study also provides important insight into how scientists might one day be able to process woody plant tissue so that it efficiently produces sugars needed for biofuels.

Woody plant material represents a vast renewable resource that has the potential to produce biofuels and other chemicals with more favourable net carbon dioxide emissions.

However, scientists haven’t yet worked out an efficient way to release its substantial store of sugars estimated to be at around 70%.

The scientific team showed  that the symptoms of ARWV infections arise from a reduction in  lignin - a complex organic polymer that forms key structural material supporting the tissues of most plants.

Using next generation sequencing (NGS)  to analysis the expression of all the genes in the rubbery apple tree branches, they discovered that phenylalanine ammonia lyase (PAL), an enzyme responsible for lignin biosynthesis was suppressed.by the plant in response to the infection

The response to ARWV infection results in the plant generating a multiple ‘small interfering RNAs, known as (vasiRNAs)

The vasiRNAs then target several of the plants own genes to be downregulated-  or degraded-   in what is assumed to be part of an antiviral defence response.

One of the genes downregulated by the plant is PAL and this leads to the decrease in lignin biosynthesis that gives the increased flexibility of the branches and facilitates the release of sugars.

The mechanism used by the apple rubbery wood virus  to alter lignin closely resembles how scientists have  been altering lignin in genetically modified trees to make it easier to process.

Despite the altered lignin the trees manage to grow normally.

Lead author Professor Simon Turner said: “Widespread genetic engineering of many plants is limited by regulatory hurdles and public opposition, and this appears particularly true for trees. These research findings offer an important contribution to that debate.

“It is apparent from our work that technologies considered as new and under regulatory oversight exhibit similarities to events considered to occur naturally.

“It seems that unbeknown to us, the ARWV infections have been performing something akin to a huge field trial”

“Since the disease has been present across the globe for many decades, even conservative estimates would suggest that many thousands of infected apple trees were propagated.

“Millions of apples from ARWV-infected trees were eaten with no known adverse health or environmental consequences despite the siRNA-induced alterations in lignin caused by the plant’s response to the virus.”

He added: “Currently, the biofuel industry uses huge areas of agricultural land to  produce corn starch that is used to generate 60 Billion litres of bioethanol.

“That’s relatively inefficient in terms of CO2 savings, but may also impact on global food production systems.

“But our increased understanding of this mechanism may one day unlock the potential to isolate the sugars within the woody tissue, making the production of biofuels much more efficient.”

An international group of leading scientists publish for updating existing standards for determining the disease-causing potential of genomic variants, harnessing insights from Genomics England rare disease participants

The work was led by scientists at Genomics England, The University of Manchester and The University of Oxford, coordinating an expert team of scientists and clinicians from academic and healthcare institutions across the UK, US and Australia. The proposed expanded guidelines will enable clinicians and researchers to take better advantage of the full range of variation in whole-genome sequence (WGS) data. They are presented in a paper, 'Recommendations for clinical interpretation of variants found in non-coding regions of the genome,' appearing today in the online edition of the open-access journal .

The recommendations address a major challenge in the diagnosis and understanding of rare disease: to date, most genetic testing has been focused on coding sequence variants – that is, those variants that disrupt regions of genes that directly encode proteins. The standards and guidelines developed over the past decade for interpreting the results of these tests – including single-gene assays and gene panels, as well as whole-exome sequencing, which encompasses all of the coding regions of the genome – have similarly focused on these types of variants.

Yet while these standards have provided a solid, evidence-driven framework for delivering consistent and reliable diagnoses using such tests, coding regions account for at most 2% of the genome. With the advent of affordable WGS and its growing use in clinical practice, ever larger numbers of potentially disease-causing variants of many different types are being detected, but without similarly systematic criteria for the community to assess their impact on disease. The result has been the proliferation of 'variants of uncertain significance’ (VUS), some of which have the same downstream clinical impact as pathogenic coding variants but work through different mechanisms and so are more difficult to assess.

In proposing updates to these guidelines for the WGS era, the authors focus explicitly on recommending adaptations and expansions that sit alongside the existing guidance, and using the same strategy of consultation and consensus-building that was used to create them. Taking advantage of Genomics England's leading expertise in clinical WGS, and data from the  participants, the recommendations were drafted by a panel of nine clinical and research scientists from major genomics laboratories in the UK. These include four of the NHS Genomic Laboratory Hubs serving the Genomic Medicine Service (GMS) and the Wellcome Centre for Human Genetics at the University of Oxford. The draft recommendations were tested by an additional group of clinical scientists using 30 test variants; refined by a group of variant interpretation experts from the UK, the  in Cambridge, Massachusetts, and the  and  in Australia, among others.

Dr. Jamie Ellingford , Lead genomic data scientist for rare disease at Genomics England, Research Fellow at The University of Manchester, and co-lead of the study said: "We are very pleased to be able to present these recommendations to the global clinical and scientific community. We hope that their adoption will serve as a useful starting point for standardising and refining the characterisation of ever more VUS. In doing so we believe that we will be able to target a subset of VUS, and provide guidelines for how to create appropriate functional evidence to interrogate pathogenicity for these variants and deliver more diagnoses for patients in the UK and around the world.

Dr Nicky Whiffin, group leader and Sir Henry Dale, fellow at the University of Oxford and co-lead of the study said: Our aim is to catalyse getting more valuable genetic diagnoses to patients. As we have access to more and more whole genome sequencing data it is becoming increasingly clear that variants in regions of the genome that do not directly encode protein play an important role in rare disease. These recommendations enable us to fully interpret these variants and harness them in the clinic, improving diagnosis and personalised treatment.

Alzheimer’s Disease is traditionally thought of as a disease of the brain cells, where a protein called Amyloid-beta (Aβ) accumulates and forms plaques. There is growing evidence that the blood supply to the brain is also affected, however, how this happens is unknown.

Now, researchers at the University of Manchester have found that a smaller version of the protein - called Amyloid-β 1-40 (Aβ 1-40) - builds up in the walls of the small arteries and reduces blood flow to the brain.

The surface of the brain is covered with small arteries, called pial arteries, that control the brain’s supply of blood and oxygen. If these arteries become narrowed for too long, the brain can’t get enough nutrients. This is one of the causes of memory loss seen in people with the disease.

When the team looked at pial arteries of older mice with Alzheimer’s that produced too much Aβ1-40, they found that the arteries were narrower compared to those of healthy mice.

This narrowing was found to be caused by Aβ 1-40 switching off a protein called BK in cells lining blood vessels. When it is working normally, BK sends a signal which causes arteries to widen.

To confirm that Aβ 1-40 stopped BK from working properly, they soaked healthy pial arteries in Aβ 1-40 and measured the signals sent by the BK protein after one hour. Aβ 1-40 weakened these signals, which caused the arteries to narrow.

The researchers now plan to investigate which part of Aβ 1-40 blocks the BK protein, so drugs to stop this from happening can be developed and tested as a much-needed treatment to prevent Alzheimer’s disease from progressing and save people the heartache of losing their memory.

Dr Adam Greenstein, lead BHF-funded researcher and Clinical Senior Lecturer in Cardiovascular Sciences at the University of Manchester said:  “To date, over 500 drugs have been trialled as a cure for Alzheimer’s disease. All of them have targeted the nerves in the brain and none of them have been successful. By showing exactly how Alzheimer’s disease affects the small blood vessels, we have opened the door to new avenues of research to find an effective treatment.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said: “This research is an important step forward in our understanding of Alzheimer’s disease. More than half a million people in the UK are living with the condition, and that number is set to rise as our population gets older. These findings could lead to a desperately needed treatment for this devastating condition.”

Publishing in the top journal and funded by the Macular Society, the researchers were able to identify early signs of the disease which could be targeted by new treatments before symptoms develop.

Scientists have long known that people with certain genes on chromosomes 1 and 10 have a 2-3-fold higher risk of developing AMD, although lifestyle factors also play a role.

The 91ֱ�� team identified higher numbers of ‘mast cells’ in the eyes of people when either of the risk genes were present, even when there were symptoms, suggesting an early mechanism in common.

They also showed the mast cells release enzymes in the back of the eye which then damage  structures underneath the retina that in time is likely to damage the retina itself.

Mast cells exist in most tissues and are one of the immune system’s  first defences against infection, especially parasitic disease and damage.

Scientists already know there are more mast cells in the choroid in people with established AMD. The current study, however, identified higher levels in people before the disease develops.

The genes on chromosome 1 are linked to a part of the immune system called the complement cascade, which is associated with a risk of  AMD.

Though the functional role of genes expressed by chromosome 10 are not known, but increased risk of AMD is.

The work was led by Prof Paul Bishop, Professor of Ophthalmology at The University of Manchester, in collaboration with Dr Richard Unwin in 91ֱ�� and Prof Simon Clark formerly of Manchester but now based at the University of Tübingen.

Dr Unwin said: “What is really exciting about this work is that we are studying tissue from people before they have signs of the disease.

“This gives us a look into the very earliest stages, and gives us hope that we can intervene to stop the disease developing and ultimately prevent loss of vision”

The scientists used health human eye tissue donated post mortem to the 91ֱ�� Eye Tissue Repository.

They identified those who are risk of developing age-related macular degeneration based on their risk genes, and discovered underlying changes in the tissue of the otherwise healthy at-risk individuals.

They collected retinal tissue from the back of donor eyes post mortem, following removal of the cornea for transplantation.

Then they took a small sample from the macula – the part of the retina responsible for central vision - and removed the cells to leave a thin layer of membrane which supports the photoreceptors called rod and cone cells and is where disease begins.

They analysed the proteins present in the membrane from 30 people using mass spectrometry, which identifies protein components based on their mass, to find differences in the tissue make-up between those with and without genetic risk of AMD.

The mass spectrometry, identified a series of enzymes which are made almost exclusively by mast cells, a type of immune cell.

Examining tissue from a further 53 people, they observed higher levels of mast cells in patients with higher disease risk.

Dr Unwin added: “We next need to look at how mast cells are activated, and whether by preventing, or clearing mast cell activation we can slow or stop disease development.

“There are several researchers and companies looking at complement mediated-therapies for AMD and while these are promising for Chr1-related disease there is no evidence that they will have an effect on Chr10 disease.

“A therapy designed to target mast cell activation as a unified mechanism could in theory treat all patients with AMD and prevent sight loss “

Geraldine Hoad, the Macular Society’s research manager, said: “This is an exciting development and we look forward to seeing further research in this area. We know lots of current treatments for wet AMD don’t work for everyone and for those with dry AMD there is no treatment at all.  Finding something that works for everyone would be an important piece of the puzzle and make a huge difference to the lives of those affected.

“While this particular study is in its early stages. it’s great to see the benefit of our investment in the 91ֱ�� Eye Tissue Repository, which is proving a vital resource for lots of research in this area.”

The paper  Mast cell infiltration of the choroid and protease release are early events in age-related 2 macular degeneration associated with genetic risk at both chromosome 1q32 and 10q26 is published in

The Macular Society is the leading sight loss charity for people affected by macular disease. If you are affected by the conditions, or know someone contact the Society's Advice and Information Service on 0300 3030 111 or email help@macularsociety.org. Alternatively for more information on macular disease visit macularsociety.org

Officially  known as Leader in Openness, the award is given by , a key body which promotes understanding of the humane use of animals in medical, veterinary, scientific and environmental research in the UK.

91ֱ�� has long been a trailblazer for openness about the work it carried out animals-  including mice, rats, fish and sheep.

It was the first University to publish an up-to-date list of non-technical summaries of its licensed projects involving animals and data on numbers of species used in licensed research, refreshed annually.

It was also among the first to publish the minutes of its animal welfare and ethics committee meetings, published a recently refreshed virtual tour of the unit, and has been acknowledged as a pioneer in its work with the media.

It is also one of the few universities to publish up-to-date case studies on outcomes of its animal research as well its work on reducing numbers, refining research and finding replacements for animals in scientific research.

Director of the Animal Unit Maria Kamper said: “Animals play a hugely important role in  scientific research aimed at helping us understand of how biological systems work so we can find ways to treat disease and understand human-  and animal- health.

“It remains a critical way for scientists to develop of new medicines and cutting edge medical technologies.

“That we’ve retained our status as a leader in animal research is testament to the hard work of both scientific and comms colleagues.”

Animal research communications lead Mike Addelman said: “We place huge importance on  openness so the public can easily find out how we work with animals and the high standards of welfare we follow. The recognition we get across the sector is testament to that.

“But we must not rest on our laurels - and are always actively looking for new and better ways to communicate our work to the public, scientists and policy makers.

“The public want easily understood accessible information about our work with animals. That way they will  make informed decisions about this important area of science.”

If you have any questions about animal research at 91ֱ��, email animal.research@manchester.ac.uk

Sellers of the supplement- known as  SAMe, which is short for -S-adenosylmethionine - claim it can help a range of conditions including joints and liver diseases, and promote emotional wellbeing.

However 91ֱ��’s Dr Jean Michel Fustin says it disrupts the biological clock in the body because it is broken down into adenine and methylthioadenosine – known toxic substances that cause a wide range of other problems including kidney and liver damage.

The study of mice, published in Communications Biology, was funded by the Medical Research Council and the Japanese Society for the Promotion of Science.

Dr Fustin and co-workers unexpectedly discovered the impact of this supplement when he was studying how the biological clock in mice is influenced by different compounds.

With SAMe, they were attempting to promote SAMe-related metabolism of the animals, though they were surprised to find an opposite inhibitive effect.

SAMe-related metabolism is very ancient, and critical for the biological clock in human and plant cells, worms, fruits flies and even bacteria.

“This worrying effect of SAMe on the body clock in mice strongly suggested it will be toxic in human as well, which we actually confirmed in human cells” said Dr Fustin.

“The health benefits that manufacturers claim are questionable to say the very least. And because it’s unclear what dose is safe, there is a good chance that a safe dose will be exceeded – if one exists at all.

“We should trust the amount of SAM our own body produces, unless there are clear clinical signs of deficiencies.”

Adenine and methylthioadenosine inhibit chemical reactions called methylations that occurs in every cell and tissue in the body. SAMe is required for these reactions, and it was expected that more SAMe would promote methylations. But the opposite turned out to be true.

Disruptions to  methylation processes have been linked to a variety of problems, including: heart attack, stroke, dementia, depression, migraines, autism, fertility, cancer, and  birth defects.

He added: “Because of the accumulation of adenine and methyltioadenosine, the consequences of chronic excess SAMe in the body are potentially very serious.

“I would advise the public to steer clear of SAMe, at the very least  until we understand more about its effect on human health.”

Every human is controlled by an internal “body clock” which orchestrate our circadian rhythms – the natural internal processes regulating our physiology every 24-hours.

This internal clock controls most of our body processes over this period, including our sleep/wake cycles, digestion, metabolism, appetite and immunity.

The paper Excess S-Adenosylmethionine inhibits methylation via catabolism to adenine is available

Published in Journal of Investigative Dermatology, the study of human and mice cells casts new light on arginase1, a protein which speeds up the rate of chemical reactions in skin cells.

They also for the first time characterise the catalyst’s role in role in the outer cells of the skin- the keratinocytes  - in the response to wound formation.

The discovery positions the enzyme’s immunological pathway as a potential drug target which could promote the repair of wounds that would otherwise heal slowly- or not at all.

Non-healing wounds include pressure sores, diabetic wounds, venous ulcers and non-healing surgical wounds and are characterised by excessive inflammation. These are a particular problem for older people and can affect as many as 1 in 20.

Scientists have long been searching for new ways to tackle the problem of delayed wound healing which represents a significant health burden on the NHS.

The scientific team show how delayed healing wounds in mice and non-healing human diabetic foot ulcers displayed reduced levels of arginase1 in the keratinocytes in the epidermis, the outermost skin layer.

hey also demonstrated the importance of epidermal arginase1 in wound healing for the ability of keratinocytes to repair and close the wound.

Scientists already know that Arginase1 is expressed by cells in the skin including immune cells and keratinocytes but the function of Arginase -1 in keratinocytes was not well understood.

The researchers now show that arginase-1 in keratinocytes is needed for production of factors such as putrescine and polyamines which are needed to help the keratinocytes migrate and proliferate across the wound to heal it.

Targeting arginase-1 as well as these downstream products with supplements restored keratinocyte function and the model systems showed that wounds healed more quickly.

Lead author Professor Sheena Cruikshank from The University of Manchester said: “Non-healing wounds are a major area of unmet clinical need that remain difficult to treat and are the source of misery for millions of people across the world.

“So an improved understanding of the biological mechanisms that promote healing is extremely important.”

In the study, acute wound biopsy samples were collected from 3 healthy volunteers and chronic wound biopsy samples from 19 patients. They were examined and wound samples analysed over 12 weeks. Transgenic mice with non-healing wounds were also used  for the study.

Professor Cruickshank added: “Our data shows a positive correlation between early expression of a  catalyst called arginase1 and healing outcomes in both mice and humans.

“We also reveal how arginase1 impacts on wound healing.”

“That means that the arginase1 pathway is an exciting target for drugs which could potentially promote wound repair which would otherwise go untreated.”

The paper A novel epidermal-specific role for arginase1 during cutaneous wound repair is available Journal of Investigative Dermatology , April 2022, Pages 1206-1216.e8. It is published in print in April

Aimed at secondary school pupils from year 7 and above - and the public - the project has been created to showcase the research and teaching in biological and biomedical sciences at 91ֱ��.

Featuring online videos, activities and exhibits, visitors to the site are able to take part in a range of activities including a virtual tour of the Firs Botanical Gardens which represent habitats from deserts to tropical forests.

They can learn how worms are used in the lab and how a living biobank for ovarian cancer is being developed at the 91ֱ�� Cancer Research Centre. You can also view the research being carried out to develop Covid-19 vaccines using plants. 

Professor Matthew Cobb looks at fifty years of genetic engineering, a subject he covered for BBC Radio Four in a programme called Genetic dreams, genetic nightmares.

You can meet Dmitri, 91ֱ�� Museum’s very own Spider-Man and find out about animal research at the University, and how it contributes to globally important breakthroughs in medical science.

Insights are provided into visualising nerve regeneration, how to grow stem cells in the lab and how we can communicate health through the medium of comics with graphic medicine.

And Professor Dan Davis tells us about his new book the ‘Secret Body’ and startling new discoveries in human biology.

Organiser Dr Shazia Chaudhry said: “We’ve been working with staff and students from across the University with this celebration of the biosciences.

“It’s all about fostering enthusiasm, fun and discovery in science. We’re very proud of what we have achieved and hope it will encourage school children and the wider public to explore science. 

“You never know, these resources could inspire our scientists of the future!”

The team, who publish in the journal Human Reproduction today (14/09/21), reveal for the first time that embryos are able to detect foreign (non-self) cells – including pathogens – in their environment.

The in vitro (procedures performed outside of the body, usually in a lab) study was funded by the and

According to the research team, when foreign cells are detected by special proteins called Toll Like Receptors (TLRs) in the embryo, it releases a type of protein called a cytokine.

Elsewhere in the body, the cytokine – called Interleukin-8 (IL8) – usually plays a role in the immune system by recruiting neutrophils to a site of inflammation.

However, its role in the relationship between embryo and mother to be is yet to be discovered.

The scientists observed the behaviour on days five and six of the embryos’ development, when it is free living in the female body, just before it implants in the lining of uterus and pregnancy begins.

Scientists already know that TLRs are found in the fallopian tube and vagina – known as the maternal tract.

Human sperm have also been shown to express TLRs 2 and 4, however, there has not been similar investigations of human embryos, until now.

Lead author Professor Daniel Brison is an Honorary Professor at The University of Manchester and Scientific Director at the

He said: “Early human embryos are highly sensitive to their local environment, however before this study, relatively little was known about how they detect and respond to specific environmental cues.

“We have discovered a signalling system generated by the embryo which allows communication with mum in a new way.

”We already knew that embryos communicate with mum when they begin to implant, but we don’t know why this new signalling happens.

“Perhaps this is an additional way of signalling an inflammatory response to the maternal tract in response to pathogens, or to modulate the implantation process and the initiation of pregnancy.

“Our data also suggests a balance between suppression and stimulation of the innate immunity response in embryos. That may reflect the need for embryo survival in the presence of benign foreign cells, versus the need for the maternal tract to respond to infection.”

The expression of Toll Like Receptors and related genes in human embryos was assessed by a literature search of published data.

Then, 25 five-day-old human embryos were cultured in the presence of Poly (I: C) and flagellin – molecules – or ligands – known to bind to Toll Like Receptors TLR3 and TLR5.

Other TLRs – expressed from the 22 known TLR genes – were not investigated by the team.

Then on day six, they measured gene expression and cytokine production and compared the results to controls.

Professor Brison added: “Though it’s very early days, this research gives us a basic understanding of what happens to the embryo in early pregnancy.

“It has implications for both natural and artificial conception, since infections can occur in both the maternal tract and In vitro Fertilisation media used for embryo culture and transfer to the uterus.

“It might one day shine a light on infertility: why some embryos do not implant into the uterus, or even help us to identify the quality of IVF embryos developing in culture.

“But much work needs to be done before we can reach that stage. And further investigations are required to determine whether the TLR stimulation response is effective during the embryonic journey in the fallopian tube.”

Human embryos surplus to treatment requirements were donated with informed consent from several Human Assisted Reproductive Technology centres.

The expression and activity of Toll-like receptors in the preimplantation human embryo suggest a new role for innate immunity is published in Human Reproduction

The team led by University of Manchester scientists  used the drugs to treat liver and kidney cells, which are commonly targeted by the virus in patients with severe disease.

Another 27 drugs also reduced replication in cells when treated prior to SARS-CoV-2 infection in the study published in the journal PLOS Pathogens and funded by Wellcome and approved by the COVID-19 Rapid Response Group at the University.

The eight drugs include the antimalarials Amodiaquine and Atovaquone; Bedaquiline which treats TB and Ebastine which treats allergic rhinitis and urticaria.

They also include Abemaciclib and Panobinostat which treat cancer, Manidipine, an antihypertensive, and vitamin D3, a health supplement bought over the counter.

“Our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID-19,” said Dr. Adam Pickard, who is an early career researcher with Professor Karl Kadler from The University of Manchester, who led the study.

Dr Pickard said: “Our identification of repurposed drugs that can stop SARS-CoV-2 replication could have enormous utility in stemming the disease.

“As these drugs are FDA-approved and with a safe dosing regime already established for use in patients, clinical trials could be initiated for these drugs within a relatively short time frame.

“The high costs and lengthy lead-in times associated with new drug development, make repurposing of existing drugs for the treatment of common and rare diseases an attractive idea.

“But we strongly urge patients taking these medications not to self-treat and that their doctors are best placed to advise how to manage their condition.”

The scientists used a version of the virus which was tagged with a protein allowing it to glow for easy identification.

They evaluated a range of human cell types for their ability to be infected and support replication. A luminescent enzyme called nano-luciferase was used to measure virus replication.

Professor Kadler added: “The different stages of the disease, from the initial infection of host cells through to virus replication and the response of the immune system, offer opportunities to identify drugs, treatments and therapies to help stop disease progression.

“Large proportions of the world’s population remain at risk of contracting COVID-19 as they wait to be vaccinated.

“So the identification of safe and easily distributed medications that can target the different stages of virus infection and replication, could reduce the spread of SARS-CoV-2 and reduce the cases of COVID-19.”

The multiple steps involved in virus infection and proliferation, could mean that  the drugs may have different molecular targets; for some, additional targets are still being clarified.

More on some of  the drugs identified in the study:

• Panobinostat, is a HDAC inhibitor that blocks DNA replication, and has been used to inhibit cell growth in the management of cancer. Panobinostat had the strongest effect on limiting SARS-CoV-2 replication whilst maintaining cell viability, and completely blocked replication of SARS-CoV-2 at all doses tested (Figure 5); however, if cells were infected prior to treatment a more modest effect on replication were observed
• Atovaquone has been identified in other studies of SARS-CoV-2 in the context of COVID-19. It is a hydroxynaphthoquinone approved by NICE for the treatment of mild to moderate pneumocystis pneumonia and as a prophylaxis against pneumocystis pneumonia. Research has suggested potential binding of atovaquone to the SARS-CoV-2 spike protein.
• Ebastine treats allergic rhinitis and chronic idiopathic urticaria and vitamin D3, is a health supplement available over the counter. The ability of  vitamin D supplementation to reduce the risk of SARS-CoV-2 infection or COVID-19 severity is unclear. In this study, vitamin D3 met the stringent cut-offs of 85% virus reduction.

The paper Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells is published in PLOS Pathogens and is available 

The University of Manchester-led study found that long-term exercise in retired racehorses – the best available model of the athlete’s heart - and in mice, triggered molecular changes in a part of the heart known as the atrioventricular (or AV) node. 

The work is the latest in a series of studies conducted by the team, showing that endurance exercise directly impacts the electrical wiring system of the heart.

Despite well-recognised cardiovascular benefits, sustained endurance exercise in athletes, footballers and other sportspeople can lead to the development of abnormal heart rhythms - known as cardiac arrhythmias, including heart block.

While benign for many people, heart block - also known as AV block - can be a precursor to more serious heart problems.

The team is the first to research the physiology of the notoriously hard-to-study AV node in athletes. The expertise to investigate the structure and function of the AV node has been developed by the 91ֱ�� team with longstanding BHF funding.

The heart’s AV node is part of its electrical conduction system controlled by the autonomic nervous system and electrically connects the atria and ventricles.

The study, published in the leading journal , found that long-term training in both horses and mice caused a reduction in key proteins, known as ion channels, that control AV node conduction.

The expression and activity of the ion channels were then investigated in detail in mice that followed a program which modelled long-term exercise training to build their fitness.

The mice were used to explore mechanisms underlying heart block in detail using approaches that would not be possible in racehorses.

Training-induced heart block and underlying ion channel changes were reversible when the exercise was stopped or when mice were given a compound known as an anti-microRNA.

Lead author Dr Alicia D’Souza, a British Heart Foundation Intermediate Fellow from The University of Manchester, said: “It’s well known that athletes are predisposed to heart block which in itself is often benign.

“But clinical research suggests that this may be ‘a canary in a coalmine’: it can flag up the risk of abnormal heart rhythms which may for example necessitate the implantation of a pacemaker in some individuals.

“For the first time our research highlights the fundamental adaptations taking place. Because we found similar effects on both mice and racehorses, it’s fair to assume this mechanism is present in humans too.”

“It must be stressed that exercise is good for you – and its benefits far outweigh the risks.”

First author Dr Pietro Mesirca, a researcher from the Institute of Functional Genomics in Montpellier said: “Understanding the physiology of the athlete’s heart is incredibly helpful: it could help us develop new interventions for heart block as well as help doctors more effectively monitor heart rhythm disturbances in top-flight professional athletes.”

Equine cardiologist and co-author of the study, Professor Rikke Buhl Professor Rikke Buhl from University of Copenhagen said: “Like human athletes racehorses suffer from cardiac arrhythmias and unfortunately also sudden cardiac death during or immediately after racing. Therefore, the results of this study have provided new insight into exercise-related cardiac changes in horses, which is of highly relevance for horse welfare as well as for owners and trainers of horses.”

The  paper ‘Intrinsic electrical remodelling underlies atrioventricular block in athletes’ is published in 

Called  and kickstarted with seed funding from the University of Manchester and other funders, the comic is an allegorical sci-fi story which reflects on the experience of young people during the pandemic.

The work by young people from South Africa, India and UK was praised by luminaries including Professor Sir Patrick Vallance, Chief Scientific Adviser to the Government and Professor Dame Anne Johnson, President of the Academy of Medical Sciences.

Project instigator and co-lead, Dr Bella Starling, honorary researcher at The University of Manchester and Director of Vocal at 91ֱ�� University Hospitals NHS Foundation Trust said: “Planet DIVOC-91 demonstrates the amazing possibilities that can happen when young people, researchers and creatives work together. Through this project young people’s voices have been directly heard by senior scientists and policy makers. The collaborative effort means that everyone has learned from each other and this has helped to bridge gaps between research communities and wider audiences. The creative outputs from this project have brought complex research topics into an accessible and engaging format.”

The young people in the project contributed presented to the UK’s Independent Sage, contributed to Academy of Medical Sciences working groups and expert meetings, and shared their views with The Lancet. They covered subjects including on adolescent wellbeing and climate change

At the start of the story earth stands on the brink of destruction with a huge asteroid hurtling towards it.

The only chance of survival is on Planet Divoc-91, a giant ‘safe house’, full of Galaxian refugee waifs and strays. But that too is now threatened with a mysterious virus.

Professor Dame Anne Johnson, President of the Academy of Medical Sciences said: “The young adults working on this comic have opened my eyes to how tough the last year has been for them. Hearing from them in their own words was really impactful for me personally.

“The voices of young adults have been severely lacking from the conversations about the wider effects of COVID-19. This group have worked so hard to add to that narrative, explaining how they are part of a generation that have missed out on so much, including all the important social interactions that we all take for granted.”

Conor Giblin, Young Editorial Team, UK said: "Planet Divoc-91 helped me to make sense of the science surrounding COVID-19 at a time when there was a lot of fear and confusion. It reassured me that other people felt the same way and gave me an opportunity to learn and combat misinformation, whilst also improving my journalism skills. It was a challenge to write about scientific concepts and social issues, but it was an enjoyable one and now I know that I'm capable of writing about a variety of different topics."

Professor Sir Patrick Vallance, Chief Scientific Adviser to the Government of the United Kingdom said: “ “Engaging young adults about their views on the pandemic is very important so I am pleased to see this creative project. This innovative project is an inspired way to connect with young adults, explore their views on the coronavirus pandemic and help understand what it means for them. I was delighted to have the opportunity to talk with some of the young adults involved in the project and was so impressed by their questions and comments. I thoroughly enjoyed our conversation and seeing and understanding how young adults tackle the issues of a fictional pandemic can help scientists, doctors and governments around the world better understand how to respond to the very real coronavirus pandemic.”

The project is managed by Vocal and Sara Kenny (Wowbagger Productions) in the UK with project teams working directly with young adults in India and South Africa.

Planet DIVOC-91 has been funded by , the , The Academy of Medical Sciences, The Science and Technology Facilities Council, Royal Society of Chemistry and The University of Manchester through the Wellcome Institutional Strategic Support Fund award. The global reach of the project has been possible by funding from Wellcome. 

The study, published in the journal , examines the impact of a SARS-CoV-2 infection on the immune system of hospitalised patients in the period after a Covid-19 infection, once they have been discharged.

The team - based at the University’s Lydia Becker Institute of Immunology and Inflammation and supported by the UK Coronavirus Immunology Consortium (UK-CIC)- identified an immunological signature occurring in some of the patients that was associated with unresolved chest x-rays, indicating those patients had a poorer clinical outcome.

The researchers therefore identified immune characteristics in convalescent COVID-19 patients are associated with negative impacts on subsequent health.

The team compiled the immune cell characteristics of over 80 convalescent patients recruited from 91ֱ�� hospitals between July and October 2020.

They found that changes to B cells - a type of lymphocyte - that occur during the peak of COVID-19 hospitalisation were largely restored by 6 months of convalescence. However, changes to T cells, another lymphocyte, persisted into COVID-19 convalescence.

91ֱ�� author Dr Joanne Konkel from The University of Manchester said: “Our study details persistent immune alterations in previously hospitalised COVID-19 patients up to 6 months after hospital discharge. Significantly, we outline an immune signature associated with poorer clinical outcomes in convalescent patients.

“Association, however, is not a causation, and what we now want to understand is what other long COVID symptoms this signature could be associated with and whether it could be used to identify the patients that should be most closely followed after hospital discharge.”

The signature present in the group of patients with the poorer clinical outcome was characterised by the team as having high levels of cytotoxic T cells – which can destroy other cells - as well as elevated production of special types of proteins called type-1 cytokines.

91ֱ�� author Dr Madhvi Menon from The University of Manchester said: “It remains to be established if these immune alterations are unique to COVID-19, or whether they are also observed following other severe respiratory infections.”

The team hoped the results can be fed into larger UK wide studies, such as the University of Leicester led post-hospitalisation COVID-19 study known as PHOSP-COVID

PHOSP-COVID aims to better understand the interactions between immune cell changes and long COVID symptoms, as well as examine the clinical utility of the immune signature defined.

“Follow-up studies will determine whether this signature can provide a tool to identify acute COVID-19 patients at risk of Long COVID, enabling close monitoring and improved clinical management.”, said Dr Menon.

91ֱ�� author Dr John Grainger from The University of Manchester and deputy Director of the Lydia Becker Institute said: “Given the vast numbers of previously infected individuals across the globe, it is vital to understand the impact of COVID-19 on the phenotype and functional potential of all immune cells.

“This will allow for better understanding of the long-term impacts of being hospitalised with COVID-19 on subsequent anti-pathogen or auto-inflammatory responses.”

The paper Alterations in T and B cell function persist in convalescent COVID-19 patients is published in

The ground-breaking study, published in ACS Nano, used cutting-edge nanotechnology uniquely developed and patented by the Nanomedicine Lab in 91ֱ��, to extract blood signals of neurodegeneration in a mouse model of Alzheimer’s disease. The study was funded by the Medical Research Council.

Tests that capture early signs of neurodegeneration in blood offer enormous potential for Alzheimer’s disease and other dementia patients to receive effective treatment or manage effectively their progressive condition before significant brain damage occurs.

Today, Alzheimer’s disease can be diagnosed by imaging techniques - brain scans - and is only possible after someone has been showing behavioural symptoms, such as memory impairment.

By the time symptoms emerge however, the pathology is already well-established in the brain - when it is often too late to treat patients effectively.

Though early markers of Alzheimer’s disease are believed to be present in blood, their minute levels make it extremely difficult to detect them - like looking for a needle in a haystack.

But thanks to the technology developed by the 91ֱ�� team, low blood signals that could non-invasively describe the onset of Alzheimer’s disease can now be magnified and analysed.

Dr Marilena Hadjidemetriou, the lead researcher of the study and Lecturer in Nano-omics said: “Hidden information in blood is likely to echo the complex cascade of events occurring in the brain of Alzheimer’s disease patients.

“We wanted to engineer a nanotechnology blood-mining platform in order to uncover this information and identify early signs of Alzheimer’s disease at the pre-disease state - before the onset of amyloid plaque formation in the brain.’’

Amyloid plaques are clumps of protein fragments which are toxic to nerve cells

The team employed nanotechnology in order to enhance the sensitivity of mass spectrometry, a proteomic technique used to analyse the patterns of proteins in blood.

They used tiny nano-sized spheres, called liposomes, as a tool to ‘fish out’ disease specific proteins from blood.

When injected in mice with Alzheimer’s Disease, nanoparticles spontaneously picked up hundreds of neurodegeneration-associated proteins onto their surfaces.

The nanoparticles were then retrieved intact from blood circulation and the molecular signatures on their surface were analysed.

Professor Kostas Kostarelos, Professor of Nanomedicine said: “This study was rather like a fishing expedition: we didn’t know what was beneath the surface of the ocean.

‘’The nano-tool we developed allowed us to see deeper into the blood proteome, identifying proteins of interest that are directly associated with neurodegeneration processes in the brain, among thousands of other blood-circulating molecules.

“We hope that these early warning signs of Alzheimer’s disease could one day be developed into a blood test and we are actively seeking validation of these signatures in human blood.’’

It was only by tracking the protein levels at different stages of Alzheimer’s disease that the team were able to identify complex disease-monitoring patterns.

Dr Catherine B. Lawrence, Senior Lecturer at the said: “We were extremely interested in the fluctuation of protein levels at different disease stages - from the pre-diseased state, to the intermediate state between amyloidopathy and cognitive symptoms and finally symptomatic disease.

“These findings indicate that single-time point blood biomarker discovery studies provide only a snapshot of the blood proteome.

‘’This could explain previously reported inconsistent results and the lack of clinically-used blood-based biomarkers for Alzheimer’s disease.’’

Professor Nigel Hooper, Associate Vice-President for Research and Director of Dementia Research at The University of Manchester said: “The technology developed opens up new possibilities for the development of novel multi-analyte blood tests to predict the onset and development of a wide range of neurodegenerative disorders.”

Paper cited: Hadjidemetriou M et al., Nanoparticle-enabled enrichment of longitudinal blood proteomic fingerprints in Alzheimer’s disease, ACS Nano.

Images shows  a nanoparticle with proteins attached and the lipid nanoparticles