Circadian Rhythm in Health and Disease

Welcome to Synchrony, where biology meets time.

Our research explores the fascinating world of circadian rhythms - biological clocks that influence our body's physiology, immunity, and responses to infections. By understanding how these daily cycles regulate virus replication and immune system activity, we aim to discover new ways to treat and prevent viral diseases. Synchrony provides real-time research updates, placing us at the cutting edge of chronobiology.

Join us as we unravel the secrets of biological timing for healthier lives.

Lab

Research Update

Daylight Powers Immunity: Body’s Clock Optimizes Neutrophil Defences Against Bacteria

A new study shows how light helps the immune system fight bacteria more effectively.

Using zebrafish, researchers found that a protein called Per2, which is activated by light, helps immune cells called neutrophils kill bacteria more efficiently during the day. Per2 helps switch on another gene called hmgb1a, which acts as an immune booster by increasing the cell’s ability to produce antibacterial molecules. This only happens during infection and depends on two signals: one from light (via a protein called BMAL1) and one from infection (via NF-κB, a well-known immune activator). Together, these signals activate hmgb1a, which then increases the production of reactive oxygen species (ROS)—toxic molecules that neutrophils use to destroy bacteria.

At night, a different protein called Cry1a acts like a brake by binding to Per2 and preventing it from turning on this immune pathway. These daily rhythms create an internal timer that helps the immune system work at its best when we’re most active. This discovery could guide future treatments by helping doctors time therapies to match the body’s natural clock.

Shella Cai

May 2025

Lucia Yi Du et al., A light-regulated circadian timer optimizes neutrophil bactericidal activity to boost daytime immunity.Sci. Immunol.10,eadn3080(2025).DOI:10.1126/sciimmunol.adn3080

Your body clock and immune system work together to control fat metabolism

A new study led by Dr Lydia Lynch reveals a crucial link between the body’s internal clock and fat metabolism. Researchers found that γδ T cells - a type of immune cell in fat tissue - produce the immune protein IL-17 in a daily rhythm, peaking during the active phase in mice. IL-17, a key cytokine involved in immune responses and inflammation, helps regulate fat storage and energy use, keeping metabolism in sync with circadian cycles.

Chronic disruptions to the circadian clock, such as those caused by shift work, can impair fat metabolism and increase the risk of fatty liver disease and type 2 diabetes. These findings provide exciting insights for developing new treatments for obesity and metabolic disorders

Alan Zhuang

March 2025

Douglas, A., Stevens, B., Rendas, M. et al. Rhythmic IL-17 production by γδ T cells maintains adipose de novo lipogenesis. Nature 636, 206–214 (2024). https://doi.org/10.1038/s41586-024-08131-3

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Clocking In for Better Drug Delivery - The Blood-Brain Barrier Gets in Sync

This study shows that our body’s internal clock, affects how the brain is protected and how medicines get into it. The blood-brain barrier (BBB) acts like a security gate, deciding what can pass from the blood into the brain.

Special cells in the BBB follow a daily rhythm that controls how well certain "gatekeeper" proteins—like P-glycoprotein (P-gp)—work. These proteins help block harmful substances but also affect how medicines move into the brain. Because of this daily rhythm, there are certain times of day when the brain is more open to receiving medicines. Important clock genes like BMAL1 and CLOCK help control this timing. Understanding this could lead to chronotherapy, where treatments are given at specific times of day to work better and cause fewer side effects. This idea is especially exciting for brain-related illnesses. By syncing medicine with the brain’s natural rhythms, we might be able to treat conditions more effectively. Future research will help fine-tune these approaches to make treatments more personalized and powerful.

Nuoxi Yu

March 2025

Kim, M., Keep, R. F., & Zhang, S. L. (2024). Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery. Circulation Research, 134(6), 727-747. https://doi.org/10.1161/CIRCRESAHA.123.323521

Timing matters! Circadian rhythm impact vaccine effectiveness

A study by Ince et al. showed that our adaptive immunity, which includes cells that remember and fight infections is influenced by the circadian rhythm. Using animal models, they discovered that immune responses are stronger when triggered during the day. Specifically, immune cells migrate more efficiently to the lymph nodes, where they activate and multiply better in the afternoon compared to at night. The study also showed that vaccinations during the day for Hepatitis A and COVID-19 (SARS-CoV-2) led to stronger immune responses, producing more antibodies and cellular response than at night. However, when the movement of immune cells was blocked, both antibody production and T-cell responses were weaker overall.

Lam On Ching

Feb 2025

Ince, L.M., Barnoud, C., Lutes, L.K. et al. Influence of circadian clocks on adaptive immunity and vaccination responses. Nat Commun 14, 476 (2023). https://doi.org/10.1038/s41467-023-35979-2

The Metastatic Spread of Breast Cancer Accelerates During Sleep

Diamantopoulou et al. investigated the impact of the circadian rhythm on the intravasation of circulating tumour cells (CTCs), which regulate breast cancer metastasis. Using mouse models of breast cancer, the study revealed oscillatory patterns of CTC shedding that peak during the rest phase. Administering insulin during the rest phase, as opposed to the active phase, reversed CTC dynamics, increasing shedding and intravasation during the active phase. Additionally, testosterone was evidenced to provide a protective effect against breast cancer metastasis, through significantly reducing the numbers of circulating CTCs at every time point and in all their forms.

Letty Laycock-Aldridge

Jan 2025

Nature. 2022 Jun 22; 607(7917):156-162. doi: 10.1038/s41586-022-04875-y

The Intrinsic Links and Therapeutic Potentials

The research bridges circadian rhythm research with cancer biology, a growing area of interest in both basic science and clinical practice. The circadian rhythm, a key regulator of physiological processes like sleep-wake, eating-fasting, and activity-rest cycles, is essential for health and homeostasis. Prolonged disruptions are linked to various diseases, including cancer. This study explores the molecular mechanisms by which circadian disturbances drive cancer progression, examining both general regulators of the circadian clock and specific cycle disruptions. Furthermore, it highlights the therapeutic potential of modulating circadian rhythms for cancer treatment, offering new avenues for chronotherapy.

Zijian Xu

2024 Dec

Zhou, L., Zhang, Z., Nice, E. et al. Circadian rhythms and cancers: the intrinsic links and therapeutic potentials. J Hematol Oncol 15, 21 (2022). https://doi.org/10.1186/s13045-022-01238-y

Ticking with the Virus: Viral Replication Regulated by the Molecular Components of the Circadian Clock

I read a study by Helene Borrmann et al. showing that HIV-1 replication follows a circadian rhythm, with its activity peaking and dipping at specific times throughout the day. Interestingly, this pattern of HIV-1 replication overlapped with the oscillation in Bmal1 levels, a key circadian gene. They also showed that the BMAL1 protein directly binds to the HIV-1 promoter region, driving viral replication. When researchers blocked BMAL1 activity using a circadian modulator, it dampened HIV-1 replication. Importantly, they identified several circadian-regulated host factors that may contribute to this rhythmic HIV-1 replication, adding a new layer to our current understanding of how the circadian clock regulates viral replication and potentially offering insights for novel drug development.

Marlin Li

Jun 2023

Borrmann H, Görkem Ulkar, Kliszczak AE, Dini Ismed, Schilling M, Magri A, et al. Molecular components of the circadian clock regulate HIV-1 replication. 2023 Jul 1;26(7):107007–7.

Shall We Give Up on the Summertime?

Daylight-saving time (DST)—advancing the clock by one hour in spring and reversing it in autumn—was first introduced to reduce energy consumption during the World War I [1]. Today, over 70 countries still observe DST. However, growing scientific and public concern has sparked debates about whether it’s time to abolish this century-old practice.

The core issue lies in the disruption of the circadian rhythm—a natural cycle of physical, mental, and behavioral changes that the body goes through in a 24-hour cycle, which is affected by light and darkness and is controlled by a small area in the middle of the brain. Even a one-hour shift can disrupt the body’s internal biological clock, causing “social jetlag,” a misalignment between the body’s internal time and the externally imposed social schedule. This misalignment impairs coordination between the brain’s master clock and peripheral clocks in organs, disturbing critical functions like sleep, metabolism, cardiovascular regulation, and immunity [2].

Cardiovascular Risks

Spring DST often leads to sleep deprivation, triggering heightened sympathetic nervous system activity. This results in vasoconstriction and elevated blood pressure, increasing the risk of heart attacks and strokes. A meta-analysis of 115,000 patients found a 5% increase in myocardial infarctions within 2 weeks of the spring DST shift [3].

Metabolic Dysregulation

DST interferes with hormonal rhythms, causing insulin to be released at inappropriate times. This reduces insulin sensitivity, raising blood glucose and increasing the risk of type 2 diabetes . Altered cortisol timing further impairs metabolism, promoting fat accumulation and metabolic syndrome [4]. A 28-hour forced desynchrony study showed postprandial glucose increased by 6% despite insulin decreased by 22%, confirming insulin resistance [5].

Mental Health Consequences

Sleep loss and mistimed cortisol release impair neurotransmitter balance and brain connectivity, reducing attention and decision-making. This contributes to more workplace injuries, traffic accidents, and, in some populations, increased depression and suicide rates. A study found a 5.7% increase in work injuries and 68 more severe injuries on the Monday after spring DST, at the same time, the suicide rates rose by 6.25%, especially in vulnerable populations [6]. DST was linked to a 6% increase in fatal traffic accidents in the US [7]. Consequently, reduced productivity, higher healthcare demands, and accident-related losses translate into significant economic costs [8].

Immune Impairment

Disruption of clock gene expression weakens immune regulation. Elevated pro-inflammatory cytokines (IL-6, TNF-α, and CRP levels by 3–29% across 24 hours) and impaired immune cell function (e.g. NK, B, T cells) reduce infection resistance and heighten autoimmune disease risk [9]. Notaboly, a meta-analysis found that sleeping less than six hours per night around vaccination significantly reduced antibody responses [10].

In conclusion, despite DST saving energy, it leads to various life burdens for human beings. Based on these evidence, some governments (for example, the European Parliament supported a proposal to end the twice-yearly clock changes in 2019) [11] and experts are now reconsidering whether the minimal benefits of DST justify these growing burdens--perhaps it’s time to abolish DST.

Shella Cai

29 Jun 2025

[1] Johns Hopkins Bloomberg School of Public Health (2023) 7 things to know about daylight saving time. Available at: https://publichealth.jhu.edu/2023/7-things-to-know-about-daylight-saving-time

[2] Samanta S, Ali SA. Impact of circadian clock dysfunction on human health. Explor Neurosci. 2022;1:4-30. doi: 10.37349/en.2022.00002.

[3] Manfredini R, Fabbian F, Cappadona R, De Giorgi A, Bravi F, Carradori T, et al. Daylight saving time and acute myocardial infarction: a meta-analysis. J Clin Med. 2019;8(3):404. doi: 10.3390/jcm8030404.

[4] Howard BV. Insulin resistance and lipid metabolism. American Journal of Cardiology. 1999 Jul 8;84(1):28–32.

[5] Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009;106(11):4453-4458. doi: 10.1073/pnas.0808180106.

[6] Osborne-Christenson EJ. Saving light, losing lives: How daylight saving time impacts deaths from suicide and substance abuse. Health Econ. 2022;31 Suppl 2:40-68. doi: 10.1002/hec.4581.

[7] Fritz J, VoPham T, Wright KP Jr, Vetter C. A chronobiological evaluation of the acute effects of daylight saving time on traffic accident risk. Curr Biol. 2020;30(4):729-735.e2. doi: 10.1016/j.cub.2019.12.045.

[8] Hafner, M., Stepanek, M., Taylor, J., Troxel, W. M., & van Stolk, C. (2017). Why Sleep Matters-The Economic Costs of Insufficient Sleep: A Cross-Country Comparative Analysis. Rand health quarterly, 6(4), 11.

[9] Zeng Y, Guo Z, Wu M, Chen F, Chen L. Circadian rhythm regulates the function of immune cells and participates in the development of tumors. Cell Death Discov. 2024;10(1):199. doi: 10.1038/s41420-024-01960-1.

[10] Spiegel, K., Rey, A.E., Cheylus, A., Ayling, K., Benedict, C., Lange, T., Prather, A.A., Taylor, D.J., Irwin, M.R. & Van Cauter, E., 2023. A meta-analysis of the associations between insufficient sleep duration and antibody response to vaccination. Current Biology, 33(5), pp.998–1005.e2. Available at: https://doi.org/10.1016/j.cub.2023.02.017.

[11] BBC News, 2019. EU votes to scrap daylight saving time from 2021. BBC News, 26 March. Available at: https://www.bbc.co.uk/news/world-europe-47704345

Research

Our Research

Our research aims to understand how circadian rhythms and their molecular components regulate viral replication and immune responses to infections. We are especially interested in how local tissue clocks affect immunity in fighting infections.

We are exploring chrono-immunotherapy as a treatment for chronic liver infections, particularly HBV, which can lead to progressive liver disease and liver cancer. Additionally, we aim to improve the effectiveness of vaccines against HBV and SARS-CoV-2 by optimising the time of day they are given. We are also investigating drugs that can adjust the circadian rhythm to boost the immune system's response to viral infections.

Members

Our Lab

Lab Members

Alan Xiaodong Zhuang

I am a principal investigator and senior research fellow in the Division of Infection and Immunity at UCL, where my research explores how our body’s internal clock shapes immune responses to viral infections.

My journey began with a PhD at the University of Birmingham, where I focused on identifying cancer targets and developing immunotherapies, including CAR-T cells and cancer vaccines. During my postdoctoral work at the University of Oxford, I became fascinated by the dynamic relationship between the host circadian clock and viral infections.

Now based in London, my lab investigates how the circadian clock coordinates immune cell behaviour and function, and how these rhythms influence interactions between immune cells and their local tissue environment. Our goal is to uncover time-based strategies for improving therapies against infection and immune disease.

Ruby Lam

I joined Zhuang’s lab as a research technician in early 2024. I hold an undergraduate degree in Biochemistry from The Chinese University of Hong Kong, where I developed a passion for research and completed an experimental project in neuroscience. During the pandemic, my interest shifted to immunology, leading me to pursue an MRes in London, where I investigated the role of pre-existing T cell immunity in SARS-CoV-2 infection.

Currently, my research focuses on how the circadian clock regulates T cell responses in chronic HBV infection and how circadian modulators impact both T cell function and viral infection.

Cindy Liu

I carried out my research project at the Zhuang Lab as part of my MSc degree. I completed my undergraduate degree at Imperial College London in Biological Sciences, and my interest shifted to immunology during my final year, when I wrote my thesis on immunometabolism in Drosophila melanogaster.

My current work involves creating transgenic circadian reporter systems in different cell types and looking at drug perturbation of the circadian clock and HBV infection. In my spare time I like to climb and play tennis.

Zijian Xu

I am currently a second-year BSc student at UCL in the Division of Infection & Immunity. This summer, I am interning at Zhuang Lab, where the focus is on circadian rhythm and viral infection. As an intern, I am now maintaining cell lines and learning essential techniques such as live luciferase assays. For my upcoming third-year project, I hope to continue working here and build on my current research experience.

Letty Laycock-Aldridge

I am currently an MRes student at the Zhuang Lab, with my primary research focusing on the role of circadian-associated proteins in liver-resident memory CD8+ T cells.

My passion for immunology began with my younger sisters’ diagnoses with multiple autoimmune conditions, inspiring me to pursue a BSc in Medical Sciences at the University of Exeter. For my undergraduate research, I explored the neural innervation of pancreatic beta cells using zebrafish models as a potential therapeutic avenue for type 1diabetes.

Outside of the lab, I enjoy music, dance, and travelling the world.

Shella Cai

I joined Zhuang's lab as a BSc summer intern student to deepen my understanding of molecular mechanisms in immunology and gain more hands-on lab experience.

I am currently studying Applied Medical Sciences at UCL, with strong interest in translational research and targeted therapy. My past experiences include basic molecular biology techniques such as RNA extraction, qPCR, and gel electrophoresis, as well as lab internship in China. My long-term goal is to pursue a PhD in immunology, focusing on disease pathogenesis and targeted therapies.

Outside the lab, I enjoy hiking, photography, and playing the piano.

Marlin Li

I am currently pursuing an MSc in Experimental and Translational Immunology at Zhuang Lab. My academic journey began with a BSc in Medical Biosciences at Imperial College London. During my undergraduate studies, I researched how natural killer cells induce pyroptosis and modulate the tumour microenvironment, sparking my interest in immunopathogenesis.

During my MSc, I became fascinated by viral pathogenesis and how viruses manipulate host mechanisms. My current work explores the role of circadian clock components in Hepatitis B virus replication.

A fun fact about me is that my late-night habits have shifted to a much healthier schedule since joining Zhuang Lab’s circadian rhythm research team.

Opp

Join Us

Are you passionate about circadian biology and its impact on health, infection, and immunity? We warmly welcome enthusiastic and motivated students interested in pursuing PhD or Master’s research within our lab. We’re also open to hosting students or visiting scholars from outside the UK for placements or internships.

If you’re curious about joining our team or would like to discuss potential projects, we’d love to hear from you.

If you have thoughts or short commentaries on circadian studies you’d like to post on our website, feel free to drop us a message!