Associate Professor Frederic Gachon

Associate Professor - Group Leader

Institute for Molecular Bioscience

Affiliate Academic

Institute for Social Science Research
Faculty of Humanities and Social Sciences
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

  • Weger, Benjamin D., Gobet, Cédric, David, Fabrice P. A., Atger, Florian, Martin, Eva, Phillips, Nicholas E., Charpagne, Aline, Weger, Meltem, Naef, Felix and Gachon, Frédéric (2021). Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms. Proceedings of the National Academy of Sciences, 118 (3) e2015803118, 1-12. doi: 10.1073/pnas.2015803118

  • Pulido, Robert S., Munji, Roeben N., Chan, Tamara C., Quirk, Clare R., Weiner, Geoffrey A., Weger, Benjamin D., Rossi, Meghan J., Elmsaouri, Sara, Malfavon, Mario, Deng, Aaron, Profaci, Caterina P., Blanchette, Marie, Qian, Tongcheng, Foreman, Koji L., Shusta, Eric V., Gorman, Michael R., Gachon, Frédéric, Leutgeb, Stefan and Daneman, Richard (2020). Neuronal activity regulates blood-brain barrier efflux transport through endothelial circadian genes. Neuron, 108 (5), 937-952.e7. doi: 10.1016/j.neuron.2020.09.002

  • Cederroth, Christopher, Gachon, Frédéric and Canlon, Barbara (2020). Time to listen: circadian impact on auditory research. Current Opinion in Physiology, 18, 95-99. doi: 10.1016/j.cophys.2020.09.005

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Available Projects

  • 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.

  • 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.

  • 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.

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Publications

Journal Article

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.

  • 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.

  • 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.

  • 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.

  • 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.