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

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

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.

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

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!