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

Contrary to common belief, blue light may not be as disruptive to our sleep patterns as originally thought - according to University of Manchester scientists.

According to the team, using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial to our health.

Twilight is both dimmer and bluer than daylight, they say, and the body clock uses both of those features to determine the appropriate times to be asleep and awake.

Current technologies designed to limit our evening exposure to blue light, for example by changing the screen colour on mobile devices, may therefore send us mixed messages, they argue.

This is because the small changes in brightness they produce are accompanied by colours that more resemble day.

The research, which was carried out on mice, used specially designed lighting that allowed the team to adjust colour without changing brightness.

That showed blue colours produced weaker effects on the mouse body clock than equally bright yellow colours.

The findings, say the team, have important implications for the design of lighting and visual displays intended to ensure healthy patterns of sleep and alertness.

The study is published in Current Biology and funded by the Biotechnology and Biological Sciences Research Council.

The body clock uses a specialised light sensitive protein in the eye to measure brightness, called melanopsin, which is better at detecting shorter wavelength photons.

This is why, say the team, researchers originally suggested blue light might have a stronger effect.

However, our perception of colour comes from the retinal cone cells and the new research shows that the blue colour signals they supply reduce the impact on light on the clock.

Dr Tim Brown, from The University of Manchester, said: “We show the common view that blue light has the strongest effect on the clock is misguided; in fact, the blue colours that are associated with twilight have a weaker effect than white or yellow light of equivalent brightness.

“There is lots of interest in altering the impact of light on the clock by adjusting the brightness signals detected by melanopsin but current approaches usually do this by changing the ratio of short and long wavelength light; this provides a small difference in brightness at the expense of perceptible changes in colour.”

He added: “We argue that this is not the best approach, since the changes in colour may oppose any benefits obtained from reducing the brightness signals detected by melanopsin.

“Our findings suggest that using dim, cooler, lights in the evening and bright warmer lights in the day may be more beneficial.

“Research has already provided evidence that aligning our body clocks with our social and work schedules can be good for our health. Using colour appropriately could be a way to help us better achieve that.”

The paper Cones support alignment to an inconsistent world by supressing mouse circadian responses to the blue colours associated with twilight is published in Current Biology.

New research has found it is not just what you eat, but when you eat that is important, knowledge which could improve the health of shift workers and people suffering from jet lag.

The Medical Research Council (MRC)-funded study, published today in the journal , is the first to identify insulin as a primary signal that helps communicate the timing of meals to the cellular clocks located across our body, commonly known as the body clock.

The team behind the research believe this improved understanding may lead to new ways to alleviate the ill-health associated with disruption to the body clock. These could include eating at specific times or taking drugs that target insulin signalling.

The body clock - also known as the circadian rhythm - is a 24-hour biological cycle that occurs individually in every cell of the body, driving daily rhythms in our physiology, from when we sleep, to hormone levels, to how we respond to medication. Our body clock is synchronised with the surrounding environment by exposure to daylight and the timing of meals. This synchrony is important for long-term health, and it is well known that disrupting your circadian rhythm by shift work or travel across time zones can be detrimental for health. Importantly, it is thought that eating at unusual times, as often occurrs during shift work and jet lag, is a major cause of body clock disruption. However, it has not previously been known exactly how the body clock senses and responds to meal timing, making it difficult to provide medical advice or interventions that might alleviate the problem.

Researchers at the MRC Laboratory of Molecular Biology (LMB) in Cambridge and The University of Manchester have now identified insulin as a primary signal that helps communicate the timing of meals to the cellular clocks across our body, and in doing so strengthen the circadian rhythm. The team’s experiments in cultured cells, and replicated in mice, show that insulin, a hormone released when we eat, adjusts circadian rhythms in many different cells and tissues individually, by stimulating production of a protein called PERIOD, an essential cog within every cell’s circadian clock.

Dr John O’Neill, a research leader at the MRC LMB who led the Cambridge research team, said: “At the heart of these cellular clocks is a complex set of molecules whose interaction provides precise 24-hour timing. What we have shown here is that the insulin, released when we eat, can act as a timing signal to cells throughout our body.”

Working with Dr David Bechtold, a senior lecturer at the University of Manchester, the researchers found that when insulin was provided to mice at the ‘wrong’ biological time - when the animals would normally be resting - it disrupted normal circadian rhythms, causing less distinction between day and night.

Dr Bechtold said: “We already know that modern society poses many challenges to our health and wellbeing - things that are viewed as commonplace, such as shift-work, sleep deprivation, and jet lag, disrupt our body clock. It is now becoming clear that circadian disruption is increasing the incidence and severity of many diseases, including cardiovascular disease and type 2 diabetes.”

Dr Priya Crosby, a researcher at the MRC LMB and lead author on the study, highlighted: “Our data suggests that eating at the wrong times could have a major impact on our circadian rhythms. There is still work to do here, but paying particular attention to meal timing and light exposure is likely the best way to mitigate the adverse effects of shift-work. Even for those who work more traditional hours, being careful about when we eat is an important way to help maintain healthy body clocks, especially as we age.”

This work was funded by the MRC with additional support from the Dutch Cancer Foundation, AstraZeneca/LMB Blue Skies Initiative and the Biotechnology and Biological Sciences Research Council (BBSRC).

The human body clock could have a significant impact on the way doctors are able to diagnose and treat asthma, according to new research.

91ֱ�� leader Dr Hannah Durrington from The University of Manchester says the work has important implications on clinical practice in asthma and other inflammatory conditions.

The study of over 300 severe asthmatics found their sputum samples were more than twice as likely to have more inflammatory cells - or eosinophils - in morning clinics than in the afternoon.

Levels of eosinophils - a biomarker in sputum - are used to guide treatment in severe asthma patients.

The study was funded by Asthma UK, the JP Moulton Charitable Trust, the North West Lung Charity and also the NIHR 91ֱ�� Biomedical Research Centre.

It is published in the American Journal of Respiratory and Critical Care Medicine.

Doctor and patients have long known that asthma symptoms are at their worst in the small hours of the morning.

But previous research has shown that the worsening symptoms are biological in cause, rather than a result of lying down.

Dr Samantha Walker, Director of Research and Policy at said: “This is an exciting preliminary study that reveals how powerful the body clock can be. If doctors and nurses know that the time of day can affect someone’s asthma they will be able to diagnose and treat them more effectively.

“Around 5.4million people in the UK have asthma and it can have a huge impact on their life, leaving them gasping for breath and at risk of a potentially fatal asthma attack. But asthma is a chronic condition with complex causes and triggers that can differ from patient to patient. More research into better ways of diagnosing asthma is urgently needed to develop better tests and to help develop more targeted treatments. For more information on how Asthma UK is supporting research and to get involved visit .”

Dr Durrington said: “These research results are really exciting but at an early stage – our aim was to understand a bit more about how the body clock affects the biochemistry of a person with asthma.

“But we are pleased because our work should help with the accurate diagnosis and treatment of asthma in the future.

“We feel it may also have important implications on other lung conditions, as well as outside respiratory medicine.

“Based on our results, different clinical decisions could be made depending on whether the patient is allocated a morning or afternoon appointment.

“And it also points towards opportunities for more personalised treatment for asthma care in the future.

“In the same way that measuring glucose levels in diabetes allows adjustment of insulin dosing, we may see asthmatics monitoring their biomarker chemicals during the day, to help inform optimum treatment times.”

The University of Manchester is home to the largest biological timing . Dr Durrington also provides an asthma clinic at Wythenshawe Hospital, 91ֱ�� University NHS Foundation Trust (MFT).

The paper, '' is published in the American Journal of Respiratory and Critical Care Medicine. DOI: 10.1164/rccm.201807-1289LE

Scientists at The Universities of Manchester and Leeds have discovered that the time of day influences the way mice respond to steroids.

from The University of Manchester, led the research which found that out of 752 genes which regulate lungs in mice, 230 genes work only in the day and only 197 at night.

And in the liver, where doctors have long thought that steroids are influential for many side effects, 1,702 genes regulate the organ in the day and a mere 299 at night in mice.

The research could one day have important implications on the way steroids - one of the most common drugs in medicine – are prescribed.

Published in the Journal of Clinical Investigation, the study is funded by the Wellcome Trust and the National Institutes of Health in the United States.

When Reverbα – a molecule that controls the time of day effect is removed, the liver flips its genes so that more genes are regulated at night than during the day.

The removal of Reverbα also seemed to have a protective effect against the build up of fat in the liver - known as fatty liver.

And that, says Professor Ray, could be important as daytime genes regulate glucose metabolism whereas night genes regulate fat metabolism.

Fatty liver is common, leads to diabetes, and can result in serious liver damage, including , if it progresses.

Professor Ray said: “Steroids are the most potent anti-inflammatory agent known to medicine. They are widely used and are very effective and used to treat a wide range of conditions.

“We can’t yet say that this research confirms that taking steroids at different times of the day will impact on things like side effects.

“But this is clearly an exciting advance in the way we understand how steroids work.”

He added: “There are experimental drugs which have been targeting Reverbα in animals.

“But now we hope to move on to measuring effectiveness and side effects on human tissue.”

REV-ERBα Couples the Circadian Clock to Hepatic Glucocorticoid Action is published in the