Overview
Background
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.
Availability
- Associate Professor Frederic Gachon is:
- Available for supervision
- Media expert
Fields of research
Qualifications
- Postgraduate Diploma, Université de la Méditerranée, Aix- Marseille II
- Postgraduate Diploma, École Nationale Supérieure de Chimie de Montpellier
- Postgraduate Diploma, Montpellier 2 University
- Doctor of Philosophy, Montpellier 2 University
Research interests
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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.
Works
Search Professor Frederic Gachon’s works on UQ eSpace
2017
Journal Article
Transcriptional regulatory logic of the diurnal cycle in the mouse liver
Sobel, Jonathan Aryeh, Krier, Irina, Andersin, Teemu, Raghav, Sunil, Canella, Donatella, Gilardi, Federica, Kalantzi, Alexandra Styliani, Rey, Guillaume, Weger, Benjamin, Gachon, Frederic, Dal Peraro, Matteo, Hernandez, Nouria, Schibler, Ueli, Deplancke, Bart and Naef, Felix (2017). Transcriptional regulatory logic of the diurnal cycle in the mouse liver. Plos Biology, 15 (4) e2001069, e2001069. doi: 10.1371/journal.pbio.2001069
2017
Journal Article
Regulation of mammalian physiology by interconnected circadian and feeding rhythms
Atger, Florian, Mauvoisin, Daniel, Weger, Benjamin, Gobet, Cedric and Gachon, Frederic (2017). Regulation of mammalian physiology by interconnected circadian and feeding rhythms. Frontiers in Endocrinology, 8 (MAR) 42. doi: 10.3389/fendo.2017.00042
2017
Journal Article
Pancreatic alpha- and beta-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression
Petrenko, Volodymyr, Saini, Camille, Giovannoni, Laurianne, Gobet, Cedric, Sage, Daniel, Unser, Michael, Masson, Mounia Heddad, Gu, Guoqiang, Bosco, Domenico, Gachon, Frederic, Philippe, Jacques and Dibner, Charna (2017). Pancreatic alpha- and beta-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression. Genes and Development, 31 (4), 383-398. doi: 10.1101/gad.290379.116
2017
Journal Article
Nuclear proteomics uncovers diurnal regulatory landscapes in mouse liver
Wang, Jingkui, Mauvoisin, Daniel, Martin, Eva, Atger, Florian, Galindo, Antonio Nunez, Dayon, Loic, Sizzano, Federico, Palini, Alessio, Kussmann, Martin, Waridel, Patrice, Quadroni, Manfredo, Dulic, Vjekoslav, Naef, Felix and Gachon, Frederic (2017). Nuclear proteomics uncovers diurnal regulatory landscapes in mouse liver. Cell Metabolism, 25 (1), 102-117. doi: 10.1016/j.cmet.2016.10.003
2016
Journal Article
Extensive regulation of diurnal transcription and metabolism by glucocorticoids
Weger, Benjamin D., Weger, Meltem, Goerling, Benjamin, Schink, Andrea, Gobet, Cedric, Keime, Celine, Poschet, Gernot, Jost, Bernard, Krone, Nils, Hell, Ruediger, Gachon, Frederic, Luy, Burkhard and Dickmeis, Thomas (2016). Extensive regulation of diurnal transcription and metabolism by glucocorticoids. PLoS Genetics, 12 (12) e1006512, e1006512. doi: 10.1371/journal.pgen.1006512
2016
Journal Article
Perturbed rhythmic activation of signaling pathways in mice deficient for Sterol Carrier Protein 2-dependent diurnal lipid transport and metabolism
Jouffe, Celine, Gobet, Cedric, Martin, Eva, Metairon, Sylviane, Morin-Rivron, Delphine, Masoodi, Mojgan and Gachon, Frederic (2016). Perturbed rhythmic activation of signaling pathways in mice deficient for Sterol Carrier Protein 2-dependent diurnal lipid transport and metabolism. Scientific Reports, 6 (1) 24631. doi: 10.1038/srep24631
2016
Journal Article
USP2-45 is a circadian clock output effector regulating calcium absorption at the post-translational level
Pouly, Daniel, Chenaux, Sebastien, Martin, Virginie, Babis, Maja, Koch, Rafael, Nagoshi, Emi, Katanaev, Vladimir L., Gachon, Frederic and Staub, Olivier (2016). USP2-45 is a circadian clock output effector regulating calcium absorption at the post-translational level. Plos One, 11 (1) e0145155, e0145155. doi: 10.1371/journal.pone.0145155
2015
Journal Article
Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver
Atger, Florian, Gobet, Cedric, Marquis, Julien, Martin, Eva, Wang, Jingkui, Weger, Benjamin, Lefebvre, Gregory, Descombes, Patrick, Naef, Felix and Gachon, Frederic (2015). Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver. Proceedings of the National Academy of Sciences of the United States of America, 112 (47), E6579-E6588. doi: 10.1073/pnas.1515308112
2015
Journal Article
Circadian dysfunction and obesity: is leptin the missing link?
Dibner, Charna and Gachon, Frederic (2015). Circadian dysfunction and obesity: is leptin the missing link?. Cell Metabolism, 22 (3), 359-360. doi: 10.1016/j.cmet.2015.08.008
2015
Journal Article
Proteomics and circadian rhythms: it's all about signaling!
Mauvoisin, Daniel, Dayon, Loic, Gachon, Frederic and Kussmann, Martin (2015). Proteomics and circadian rhythms: it's all about signaling!. Proteomics, 15 (2-3), 310-317. doi: 10.1002/pmic.201400187
2014
Journal Article
Local renal circadian clocks control fluid-electrolyte homeostasis and BP
Tokonami, Natsuko, Mordasini, David, Pradervand, Sylvain, Centeno, Gabriel, Jouffe, Celine, Maillard, Marc, Bonny, Olivier, Gachon, Frederic, Gomez, R. Ariel, Sequeira-Lopez, Maria Luisa S. and Firsov, Dmitri (2014). Local renal circadian clocks control fluid-electrolyte homeostasis and BP. Journal of the American Society of Nephrology, 25 (7), 1430-1439. doi: 10.1681/ASN.2013060641
2014
Journal Article
Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver
Mauvoisin, Daniel, Wang, Jingkui, Jouffe, Celine, Martin, Eva, Atger, Florian, Waridel, Patrice, Quadroni, Manfredo, Gachon, Frederic and Naef, Felix (2014). Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver. Proceedings of the National Academy of Sciences of the United States of America, 111 (1), 167-172. doi: 10.1073/pnas.1314066111
2014
Journal Article
Chronopharmacology: new insights and therapeutic implications
Dallmann, Robert, Brown, Steven A. and Gachon, Frederic (2014). Chronopharmacology: new insights and therapeutic implications. Annual Review of Pharmacology and Toxicology, 54 (1), 339-361. doi: 10.1146/annurev-pharmtox-011613-135923
2013
Journal Article
The circadian clock coordinates ribosome biogenesis
Jouffe, Celine, Cretenet, Gaspard, Symul, Laura, Martin, Eva, Atger, Florian, Naef, Felix and Gachon, Frederic (2013). The circadian clock coordinates ribosome biogenesis. Plos Biology, 11 (1) e1001455, e1001455. doi: 10.1371/journal.pbio.1001455
2011
Journal Article
Proline- and acidic amino acid-rich basic leucine zipper proteins modulate peroxisome proliferator-activated receptor alpha (PPAR alpha) activity
Gachon, Frederic, Leuenberger, Nicolas, Claudel, Thierry, Gos, Pascal, Jouffe, Celine, Olela, Fabienne Fleury, du Jeu, Xavier de Mollerat, Wahli, Walter and Schibler, Ueli (2011). Proline- and acidic amino acid-rich basic leucine zipper proteins modulate peroxisome proliferator-activated receptor alpha (PPAR alpha) activity. Proceedings of the National Academy of Sciences of the United States of America, 108 (12), 4794-4799. doi: 10.1073/pnas.1002862108
2011
Journal Article
The role of circadian timing system on drug metabolism and detoxification
Gachon, Frederic and Firsov, Dmitri (2011). The role of circadian timing system on drug metabolism and detoxification. Expert Opinion On Drug Metabolism and Toxicology, 7 (2), 147-158. doi: 10.1517/17425255.2011.544251
2010
Journal Article
Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF
Wang, Qing, Maillard, Marc, Schibler, Ueli, Burnier, Michel and Gachon, Frederic (2010). Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 299 (4), R1013-R1019. doi: 10.1152/ajpregu.00241.2010
2010
Journal Article
Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation?
Gachon, Frederic and Bonnefont, Xavier (2010). Circadian clock-coordinated hepatic lipid metabolism: only transcriptional regulation?. Aging, 2 (2), 101-106. doi: 10.18632/aging.100123
2010
Journal Article
Circadian clock-coordinated 12 hr period rhythmic activation of the IRE1 alpha pathway controls lipid metabolism in mouse liver
Cretenet, Gaspard, Le Clech, Mikael and Gachon, Frederic (2010). Circadian clock-coordinated 12 hr period rhythmic activation of the IRE1 alpha pathway controls lipid metabolism in mouse liver. Cell Metabolism, 11 (1), 47-57. doi: 10.1016/j.cmet.2009.11.002
2007
Journal Article
Crosstalk between xenobiotics metabolism and circadian clock
Claudel, Thierry, Cretenet, Gaspard, Saumet, Anne and Gachon, Frederic (2007). Crosstalk between xenobiotics metabolism and circadian clock. Febs Letters, 581 (19), 3626-3633. doi: 10.1016/j.febslet.2007.04.009
Supervision
Availability
- Associate Professor Frederic Gachon is:
- Available for supervision
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Available projects
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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.
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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.
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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.
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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.
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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.
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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.
Supervision history
Current supervision
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Doctor Philosophy
Host-Microbe Interactions and the circadian clock in Liver Disease
Associate Advisor
Other advisors: Professor Matt Sweet, Dr Meltem Weger, Dr Benjamin Weger
Media
Enquiries
Contact Associate Professor Frederic Gachon directly for media enquiries about:
- Chrononutrition
- Circadian clocks
- Circadian rhythms
- Feeding rhythms
- Liver
- Metabolic Diseases
- sex specific physiology
- System biology
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