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INRAE

24, chemin de Borde Rouge -Auzeville - CS52627 31326 Castanet Tolosan cedex - France

Last update: May 2021

Menu Logo Principal logo Université Clermont Auvergne & associés

Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

Pierre Fafournoux

Team leader

Field of research and research activities

My research project is originated from the observation that mammals cannot synthesize essential amino acids. As a consequence, individuals have to adjust several physiological functions in order to adapt to dietary amino acid deficiency. Such a nutritional situation is very common for omnivorous mammals living in the wild. Preliminary observations suggested that amino acids by themselves are involved in the control of physiological functions. Taken together, these observations have led us to wonder whether amino acids regulate physiological functions through the control of gene expression. In order to answer that question, our project consisted of 3 main objectives: 1- To identify the molecular mechanisms involved in the regulation of gene expression in response to amino acid limitation; 2- To characterize the role of the identified amino acid-regulated signaling pathways in the control of physiological functions; 3- To integrate these data in more complex nutritional or pathological situations.

Major scientific achievements

-First Identification of the Amino Acid Responsive Elements

-Demonstration that amino acid limitation regulates physiological function through the control of gene expression.

-Establishment that the protein kinase GCN2, activated upon amino acid limitation, controls

 feeding behavior to maintain amino acid homeostasis in response to amino acid-imbalanced diet.

-Demonstration that perinatal undernutrition affects the methylation and expression of the leptin gene in adults. This study is an example of a molecular rationale linking transient environmental influences to permanent phenotypic consequences.

-Optimization of a novel nutrition-based regulatory system: a compelling resource in gene therapy

 

Five most relevant publications

1) Bruhat, A., Jousse, C., Carraro, V., Reimold, A., Ferrara, M., and Fafournoux, P. (2000). Amino acids control mammalian gene transcription: activating transcription factor 2 is essential for the amino-acid responsiveness of the CHOP promoter. Mol Cell Biol, 20(19),7192-7204.

2) Maurin AC,, Jousse C, Averous J, Parry L, Bruhat A, Cherasse Y, Zeng H, Zhang Y, Harding HP, Ron D, Fafournoux P. (2005) The GCN2 kinase biases feeding behavior to maintain amino-acid homeostasis in omnivores, Cell Metabolism 1; 273-277.

3) Jousse C, Parry L, Lambert-Langlais S, Maurin AC, Averous J, Bruhat A, Carraro V, Tost J, Letteron P, Chen P, Jockers R, Launay JM, Mallet J, Fafournoux P. (2011). Perinatal undernutrition affects the methylation and expression of the leptin gene in adults: implication for the understanding of metabolic syndrome. FASEB J. 25 ; 3271-3278

4) Maurin AC, Benani A, Lorsignol A, Brenachot X, Parry L, Carraro V, Guissard C, Averous J, Jousse C, Bruhat A, Chaveroux C, B'chir W, Muranishi Y, Ron D, Pénicaud L, Fafournoux P. Hypothalamic eIF2α signaling regulates food intake. Cell Reports. 2014 Feb 13;6(3):438-44

5) Cédric Chaveroux, Alain Bruhat, Valérie Carraro, Céline Jousse, Julien Averous, Anne-Catherine Maurin, Laurent Parry, Florent Mesclon, Yuki Muranishi, Aline Meulle, Patrick Baril, Anh Do Thi, Philippe Ravassard, Jacques Mallet, and Pierre Fafournoux (2016) Tuning transgene expression with an artificial diet: a compelling resource in gene therapy. Nature Biotechnology 2016 Jul;34(7):746-51.

 

Patents:

- Fafournoux P; Bruhat A; Jousse C; Maurin AC; Averous J. New expression cassette comprising a gene of interest linked to an inducible promoter comprising cis-acting regulator element regulator sequence and a minimal promoter, usefull for e.g. treating diseases by gene therapy and genetic disease. Patent numbers : FR2982277-A1 (10 May 2013); WO2013068096-A& (16 May 2013); EP2776568-A1 (17 Sep 2014); US2014322184-A1 (30 octobre 2014). « Inducible expression cassette, and uses thereof » filed in 2012 by INRA and CNRS

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