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Associate Professor Frederic Gachon

Associate Professor - Group Leader

Institute for Molecular Bioscience
f.gachon@imb.uq.edu.au
+61 7 334 62017

Overview

Frédéric Gachon received his PhD in 2001 from the University of Montpellier (France). Between 2001 and 2006, he performed his post-doctoral training with Prof. Ueli Schibler at the department of Molecular Biology of the University of Geneva (Switzerland), where he started to work on the regulation of physiology by the circadian clock. In 2006, he worked at the Institute of Human Genetic in Montpellier (France) as a junior group leader before continued his career in Switzerland as an Assistant Professor in the Department of Pharmacology of the University of Lausanne (2009-2012) and as a group leader at the Nestlé Institute of Health Sciences, Lausanne (2012-2018). He finally joined the Institute of Molecular Bioscience of the University of Queensland as an Associate Professor in 2019. During all these years, research of the Gachon group focussed on the understanding of the role of feeding and circadian rhythms on mouse and human physiology, contributing to the fundamental basis for chronopharmacology and chrononutrition.

Research Interests

  • Physiology of circadian rhythms
    Circadian clocks have been conserved throughout the evolution, allowing the adaptation of the physiology to the time of day in an anticipatory way. As a demonstration of their crucial role, perturbation of the circadian clock leads to numerous pathologies including obesity, type 2 diabetes and cancer. Our goal is to determine how the circadian clock regulates mammalian physiology and understand how the perturbation of the circadian clock leads to pathologies. We use a wide variety of techniques, including animal biology, molecular biology, biochemistry, genomics, proteomics and bioinformatic analysis of the data to make conclusions at the biological system level.

Research Impacts

Our research group has made many significant contributions to the field. The first of these was the description of the control of xenobiotic detoxification by the circadian clock, constituting a breakthrough in the field of chronopharmacology. Other contributions are related to the characterisation of the mechanisms of transcriptional regulation by the circadian clock, which led to the first description of rhythmic mRNA translation that is regulated by circadian and feeding rhythms. This rhythmic translation controls ribosome biogenesis that contributes to liver size fluctuations. Because mRNA expression is often insufficient to predict gene expression, we invested a lot of effort in characterizing the impact of the circadian clock on protein accumulation. This led to the first high scale proteomic analyses of mouse liver and its nuclear compartment, establishing the regulation of the rhythmic protein abundance occurs primarily at the post-translational level. My work showed that less than 50% of the rhythmic proteins are encoded by rhythmic mRNA, while protein transport and secretion play a central role in the regulation proteins levels. We have also have recently studied the impact of the microbiome on rhythmic physiology. This work showed that the microbiome mainly impacts sexual maturation and growth hormone secretion, affecting gene expression and metabolism in digestive tissues in a sex-specific manner. This observation can explain the previously described phenotypes of germ-free mice including resistance to obesity and cancer. On top of this basic research, our research has also examined the impact of the circadian clock on the metabolism of glucose, lipids and vitamins, in particular in the liver, kidney and pancreas. Human studies corroborated my animal research and provided a basis for translation of our research, in particular in the domain of chrononutrition.

Qualifications

  • Diploma of Advanced Studies in Health Biology, Montpellier II University
  • Engineering Diploma, ENSCM
  • University Diploma of Technology, Aix-Marseille III
  • Doctor of Philosophy, Montpellier II University

Publications

  • Journal Article: Understanding circadian dynamics: current progress and future directions for chronobiology in drug discovery

    Weger, Meltem, Weger, Benjamin D. and Gachon, Frédéric (2023). Understanding circadian dynamics: current progress and future directions for chronobiology in drug discovery. Expert Opinion on Drug Discovery, 18 (8), 893-901. doi: 10.1080/17460441.2023.2224554

  • Journal Article: Mice with humanized livers reveal the role of hepatocyte clocks in rhythmic behavior

    Delbès, Anne-Sophie, Quiñones, Mar, Gobet, Cédric, Castel, Julien, Denis, Raphaël G. P., Berthelet, Jérémy, Weger, Benjamin D., Challet, Etienne, Charpagne, Aline, Metairon, Sylviane, Piccand, Julie, Kraus, Marine, Rohde, Bettina H., Bial, John, Wilson, Elizabeth M., Vedin, Lise-Lotte, Minniti, Mirko E., Pedrelli, Matteo, Parini, Paolo, Gachon, Frédéric and Luquet, Serge (2023). Mice with humanized livers reveal the role of hepatocyte clocks in rhythmic behavior. Science Advances, 9 (20) eadf2982, 1-14. doi: 10.1126/sciadv.adf2982

  • Journal Article: Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock

    Bignon, Yohan, Wigger, Leonore, Ansermet, Camille, Weger, Benjamin D., Lagarrigue, Sylviane, Centeno, Gabriel, Durussel, Fanny, Götz, Lou, Ibberson, Mark, Pradervand, Sylvain, Quadroni, Manfredo, Weger, Meltem, Amati, Francesca, Gachon, Frédéric and Firsov, Dmitri (2023). Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock. Journal of Clinical Investigation, 133 (8) e167133, 1-17. doi: 10.1172/JCI167133

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Grants

View all Grants

Available Projects

  • Improving the recovery of ICU patients through the preservation of their circadian physiology

    The ICU of the Future project is a TPCH Critical Care Research Group project, employing a collaborative multi-disciplinary and intersectoral approach, putting patients at the centre of ICU design. The purpose is to fundamentally redesign the ICU environment to not only achieve survival, but provide a superior recovery experience, optimised outcomes of care and quality of life beyond, incorporating the patient’s needs and wishes into an improved ICU design. The project team is working with ICUs across Metro North, but also partnering with other ICUs across the state and nationally. The project team, comprising clinicians and researchers (including nursing, allied health, psychology, psychiatry and intensive care specialists), have worked closely with patients and world leading industry partners such as Philips, Getinge, Ascom and Lendlease, to reconceptualise intensive care, co-designing an ultra-modern recovery focussed ICU bedspace. Using advanced technology and evidence-based design, the proposed new bedspace tailors the care environment to patient’s shifting clinical needs and personal preferences.

    The adverse impact of critical illness and an ICU admission on patients’ circadian rhythms are well known. The sleep deprivation experienced by patients spending prolonged periods in an ICU and the loss of their normal circadian rhythms have been documented in multiple studies. However, there is scant information about the impact of the physical and sensory environment on patients circadian rhythms, and we are not aware of any studies investigating how a modified / improved ICU bedspace environment impacts on patients circadian rhythms. Similarly, there is limited information available about the longer term impact this loss of circadian rhythm has on patients, and whether it impacts on their ability to recover physically, cognitively and/or psychologically.

    This PhD project is a part of the larger ICU of the Future project. It is a collaborative project with the UQ IMB, aiming to analyse how the ICU environment impacts on patients’ circadian rhythms and how an improved environment impacts the circadian rhythms of patients during their ICU admission, and how this affects the recovery of their physical, cognitive and mental health.

  • Specific role of the circadian clocks in the different liver cell types and how they interact

    The goal of this project is to define the specific role of the circadian clock in the different cell types of the liver (hepatocytes, stellate cells, endothelial cells...) and how the perturbation of these cell-specific circadian clock is involved in liver pathologies. This project will involve genetically modified animal models, RNA-sequencing, protein analysis and evaluation of metabolic parameters.

  • Regulation of liver protein secretion and its regulation by circadian and feeding rhythms

    While most of blood proteins are secreted by the liver, how they are secreted is still not clear, as well as the regulation of this secretion. Our previous experiments showed that liver protein secretion is rhythmic and regulated by feeding rhythms in both mouse and human. Using newly generated animal model and experiments in cultured cells, this project will decipher the mechanisms involved and the consequences of the perturbation of this rhythmic secretion on animal physiology.

View all Available Projects

Publications

Journal Article

Other Outputs

  • A role for caveolar proteins in regulation of the circadian clock

    Fonseka, Sachini, Weger, Benjamin D., Weger, Meltem, Martel, Nick, Hall, Thomas Edward, Varasteh Moradi, Shayli, Gabriel, Christian H., Kramer, Achim, Ferguson, Charles, Fernández-Rojo, Manuel A., Alexandrov, Kirill, Rawashdeh, Oliver, McMahon, Kerrie-Ann, Gachon, Frederic and Parton, Robert G. (2022). A role for caveolar proteins in regulation of the circadian clock.

  • Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology

    Delbès, Anne-Sophie, Quiñones, Mar, Gobet, Cédric, Castel, Julien, Denis, Raphaël G. P., Berthelet, Jérémy, Weger, Benjamin D., Challet, Etienne, Charpagne, Aline, Metairon, Sylviane, Piccand, Julie, Kraus, Marine, Rohde, Bettina H., Bial, John, Wilson, Elizabeth M., Vedin, Lise-Lotte, Minniti, Mirko E., Pedrelli, Matteo, Parini, Paolo, Gachon, Frédéric and Luquet, Serge (2022). Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology.

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Improving the recovery of ICU patients through the preservation of their circadian physiology

    The ICU of the Future project is a TPCH Critical Care Research Group project, employing a collaborative multi-disciplinary and intersectoral approach, putting patients at the centre of ICU design. The purpose is to fundamentally redesign the ICU environment to not only achieve survival, but provide a superior recovery experience, optimised outcomes of care and quality of life beyond, incorporating the patient’s needs and wishes into an improved ICU design. The project team is working with ICUs across Metro North, but also partnering with other ICUs across the state and nationally. The project team, comprising clinicians and researchers (including nursing, allied health, psychology, psychiatry and intensive care specialists), have worked closely with patients and world leading industry partners such as Philips, Getinge, Ascom and Lendlease, to reconceptualise intensive care, co-designing an ultra-modern recovery focussed ICU bedspace. Using advanced technology and evidence-based design, the proposed new bedspace tailors the care environment to patient’s shifting clinical needs and personal preferences.

    The adverse impact of critical illness and an ICU admission on patients’ circadian rhythms are well known. The sleep deprivation experienced by patients spending prolonged periods in an ICU and the loss of their normal circadian rhythms have been documented in multiple studies. However, there is scant information about the impact of the physical and sensory environment on patients circadian rhythms, and we are not aware of any studies investigating how a modified / improved ICU bedspace environment impacts on patients circadian rhythms. Similarly, there is limited information available about the longer term impact this loss of circadian rhythm has on patients, and whether it impacts on their ability to recover physically, cognitively and/or psychologically.

    This PhD project is a part of the larger ICU of the Future project. It is a collaborative project with the UQ IMB, aiming to analyse how the ICU environment impacts on patients’ circadian rhythms and how an improved environment impacts the circadian rhythms of patients during their ICU admission, and how this affects the recovery of their physical, cognitive and mental health.

  • Specific role of the circadian clocks in the different liver cell types and how they interact

    The goal of this project is to define the specific role of the circadian clock in the different cell types of the liver (hepatocytes, stellate cells, endothelial cells...) and how the perturbation of these cell-specific circadian clock is involved in liver pathologies. This project will involve genetically modified animal models, RNA-sequencing, protein analysis and evaluation of metabolic parameters.

  • Regulation of liver protein secretion and its regulation by circadian and feeding rhythms

    While most of blood proteins are secreted by the liver, how they are secreted is still not clear, as well as the regulation of this secretion. Our previous experiments showed that liver protein secretion is rhythmic and regulated by feeding rhythms in both mouse and human. Using newly generated animal model and experiments in cultured cells, this project will decipher the mechanisms involved and the consequences of the perturbation of this rhythmic secretion on animal physiology.

  • Circadian regulation of protein glycosylation

    Protein glycosylation plays an important role in protein maturation, trafficking and secretion. Our recent evidences suggest that glycosylation and synthesis of gangliosides could be a rhythmic process regulated by the circadian clock. The goal of this project is to characterize this never described circadian process as well as the involved mechanisms.

  • Impact of circadian clock disruption on the development, growth, sleep and learning of the zebra finch

    The circadian clock orchestrates virtually all aspects of physiology so that organisms may better anticipate predictable daily changes caused by the Earth’s rotation. Consequently, disruption of circadian rhythms, or chronodisruption, is associated with several pathological or psychological conditions. Nevertheless, most research has focussed on nocturnal rodents, with little information on diurnal animals. This project proposes to study the impact of chronodisruption on the physiology of a diurnal animal: the common Australian zebra finch (Taeniopygia guttata). In collaboration with Prof. Kate Buchanan (Deakin University), we will study the impact on chronodisruption on the physiology of the zebra finch: reproduction, development, growth, sleep and learning. This project will provide a global and comprehensive study of the impact of chronodisruption on the life cycle of a diurnal passerine. This will allow the evaluation of the impact of environmental perturbation on the life cycle of this bird and, more globally, provide new information of the impact of chronodisruption on diurnal animals.

  • Role of the autonomic nervous system in the rhythmic regulation of animal physiology by light

    Light exposure has a strong influence on animal physiology. However, its effect on development and aging are still poorly described, as well as the involved mechanisms remain unknown. The goal of this project is to describe these mechanisms and study the impact of adverse light exposure on development, metabolism and aging.

This staff member is a UQ Expert for media in the following fields:

Circadian rhythms, Circadian clocks, Chrononutrition, Liver, Metabolic Diseases, Feeding rhythms, System biology, sex specific physiology

They are happy to lend their expertise to your articles or broadcasts and share their research discoveries and insights with the community via media channels.

For additional assistance with story ideas, general advice and information or help with seeking further experts, please email the UQ Media Team or telephone (07) 3365 1120.

Links

ResearcherID: H-3111-2019

ORCID: 0000-0002-9279-9707

Scopus ID: 57203509435

Google Scholar ID: j0dnT-0AAAAJ

Personal Profile: Link

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