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Jean Marie FrançoisProfessor

Jean Marie François
Professeur exceptional Class

Microbial Physiology and Functional genomics of yeasts and filamentous fungi–PHYGE-

+33 (0) 5 61 55 94 92 or +33 (0) 5 61 28 57 55

Toulouse Biotechnology Institute chemical engineering and Toulouse White Biotechnology, INSA de Toulouse
135 avenue de Rangueil
31077 Toulouse cedex 4 - FRANCE

fran_jm @ insa-toulouse.fr or jean-marie.francois @ inrae.fr

 

orcid n° 0000-0001-9884-5535

 

Key words: Microbial physiology, Synthetic microbiology, Industrial Microbiology, Bionanotechnology

 

CV

  • 1983, Engineer in Agronomy and Biological Chemistry , Catholic University Louvain (Belgium)
  • 1988, Ph D in Biochemistry and Agronomy, Catholic University Louvain and Institute Claude de Duve (Belgium) under the supervision of late Prof Henry Gery Hers and Prof Andre Goffeau
  • 1988-1991, Postdoctoral trainings at North Carolina State University (Prof Dr K. Tatchell), Bordeaux University II
  • 1991 -1992, Associate professor at University Catholic of Louvain and Invited lecturer at University Sao-Paulo, Brazil (Department of Biological Chemistry)
  • 1992-1993: Associate professor at Catholic University of Louvain-La-Neuve, department of physiological biochemistry
  • Since 1993, Professor of Biochemistry, Microbial Physiology and BioNanotechnology at National Institute of Applied Sciences and Federal University of Toulouse.
  • Since 2009, Professor Exceptional class
  • Since 2017, Editor in Chief of BMC Biotechnology & Biofuels
  • Since 2018, Specialty Editor in Frontiers Bioengineering Biotechnology, section Synthetic biology

 

RESEARCH TOPICS

The research activity of the team 'Integrative physiology and functional genomics of microbial systems (yeasts and filamentous fungi, PHYGE) that I am the leader at TBI since 1994 focuses on an integrative approach of the physiology of microorganisms to environmental constraints, relevant in an industrial context. Our research encompasses three major thematic. Thematic 1 deals with the organization and structural and molecular reorganization of the yeast cell wall in response to environmental and technological constraints. Thematic 2 focuses on questions of functional genomics, with priority being given to the study of cellular heterogeneity by investigating whether the genetic or the metabolic origin of heterogeneity in cellular population. Thematic 3 dealt with the refactoring of microbial metabolic network using synthetic and systems biology tools with the objectives to construct microbial cell factories enabling to efficiently convert renewable carbon sources into bio-based products. In addition, my team is collaborating with many industrial partners among which a long-standing collaboration exists with the industrial companies Adisseo SAS and Lallemand Inc. We are also collaborating with local (IBPS, LAAS-CNRS, Biomathematics and Biostatistics of INSA /UPS), national (Ecole Supérieure Chimie Physique Paris, INRA Montpellier) and international (University of Frankfurt, TU Dresden Germany; BOKU- Wien; University of Delaware, USA; Univ. Campinas Brazil) teams. In general, our research activities aim at acquiring knowledge that feeds into more application-oriented projects in industrial biotechnology, such as proposing strategies to optimize the "metabolic" capacity, modify the structure of microorganism walls or express a "suicide" system to limit the heterogeneity of the microbial population during a production process. Research in my team is currently supported by national grants from ANR (Agence National de la recherché) and PIA (Projet Investissement d’Avenir) and EU (Cost, Eranet 2020) as well as from industrial supports.

 

I am also running industrial-oriented and financially supported projects whose maturity level (TRL) is at level 4 or 5 and which require methodological developments, based on the scientific knowledge acquired through the work carried out by my team at TBI. Currently, these researches are supported by Industrial and TWB grants

 

Beside this main activity, I was also head of a BioNanobiotechnology network in Toulouse that develops interdisciplinary researches on Bio-patterning and integrated Bio-detection from 2009 to 2014. This interdisciplinary activity with Bioengineers, physicists and chemists led me to create DENDRIS (www.dendris.fr), a start-up, which is exploiting Nanotechnology tools for molecular diagnostic and nanomedicine and holds several patents in biochips conception for diagnostic purposes.

 

Since the beginning of my career, I have supervised 32 PhD students and have had the privilege of hosting 32 postdocs with more than half of whom have become researchers or professors while the other half have been hired in the private sector.

 

 

TEACHING

  • Since 1993:Teaching Microbial Physiology and functional genomics at INSA
  • Since 2015:Teaching Biology and Bioengineering at Bio-process Engineers at Ecoles des Mines Albi –Carmaux
  • Since 2015: Lecturer at ESPCI (Ecole Supérieure Physique Chimie de Paris) on Systems and Synthetic biology to Master 1
  • From 2002 -2010: Teaching of Molecular Biology and Nanobiotechnology at Physical and Mathematical Engineers
  • From 2002 -2015; Teaching Bionanotechnology at MASTER 2 Diagnostic University Toulouse
  • 2001 to 2004: Invited lecturer at Institute Polytechnic Mexico: Teaching on DNA arrays technology and application for functional microbial genomics,
  • 2001 to 2005: Invited lecturer at University of Qingdao, (China) 2001 - 2005 : Lecture in Microbial Physiology and Bioengineering technologies
  • 2004: Invited lecturer at University de Ho Chi Minh (Vietnam) 2004: lecture on DNA arrays technology and application for functional genomics,
  • 2006-2007: Invited lecturer at University de Biotecnologia y Oenologia, Tarragona, (Spain) 2006: DNA arrays technology and application for functional microbial genomics,
  • 2009 -2011: Invited lecturer at New Sofia University (Bulgaria) (Erasmus school) (2009 -20912 Lecture on Genomics and post-genomics in Microbiology 

 

PUBLICATIONS

Author of > 200 peer-review papers in Scientific Journal, 5 text books, 18patents, Hi: 61 and 13817 citation (as in Scholar Google on June 2021)

 

 

Publications since 2015

Thematic 1: Fungal cell wall assembly and regulation

  1. Formosa, C., lachaize, V., Galès, C., MP Roles, Martin-Yken, H., François, JM., Duval, RE & Dague, E (2015) Mapping HA-taggeed protein at the surface of living cells by Atomic force microscopy. Mol. Recognit., 28: 1-9.
  2. François, J.M (2015) Cell Surface Interference with Plasma Membrane and Transport Processes in Yeasts in Advances in Experimental Medicine and Biology, Volume 892 pp 11-31, doi: 10.1007/978-3-319-25304-6_2. Springer Verlag
  3. Schiavone, M., Castex, M., Siekowzki, N., Dague, E & François, J. (2015). Atomic force microscopy allows revealing effects of autolysis processes and differences in nanomechanical properties of industrial yeast strains FEMS Yeast Res., 15, (2) 1-9.
  4. Ran L., Formosa, , Dagkessamanskaia, A., Dague, E. François, J & Martin-Yken, H. (2015). Combining Atomic Force Micsroscopy and genetics to investigate the role of Knr4 in Saccharomyces cerevisiae sensitivity to K9 killer toxin. Lett. App. NanoBioSc., 4, 306-315
  5. Julien, S., Tondl, P., Durand,F., Dagkessamanskaia,A., van Tilbeurgh, H., Francois,J, Mourey, L., Zerbib, D., Yken-Martin, H. and Maveyraud, L. (2015) Crystallization and preliminary crystallographic studies of the structured core domain of Knr4 from Saccharomyces cerevisiae, Acta Cryst F,
  6. Martin-Yken, H., François, J. & Zerbib, D (2016) Knr4: a disordered hub protein at the heart of fungal cell wall signalling. Cellular Microbiology, 18(9) 1217-1227
  7. Schiavone, M., Elsztein, C., Formosa-Dague, C., Teste, M-A., Martin-Yken, H., Morais, M.A.jr, Dague, E. & François, J. (2016). An Atomic Force Microscopy study of the response of the yeast Saccharomyces cerevisiae to ethanol stress. Appl.Env Microbiol., 82: 4789-4801 Doi: 10.1007/s00294-013-0411-0
  8. Schiavone, M., Déjean, , Sieczkowski, N., Castex, M., Dague, E. and François J M (2017) Integration of biochemical, biophysical and transcriptomics data for investigating the structural and nanomechanical properties of the yeast cell wall. Frontiers in Microbiology, 8: 1809; DOI: 10.3389/fmicb.2017.01806
  9. Schiavone, M., Sieczkowski, N., Castex, M., Dague, E. & François J.M (2019) AFM dendritips functionalized with molecular probes specific to cell wall polysaccharides as a tool to investigate cell surface structure and organization. The Cell Surface, 5 : 100027. DOI: 10.1016/j.tcsw.2019.100027
  10. Bouyx, C., Schiavone, M., Teste, M-A., Swierckowki, N., Julien, A. and Francois, J. (2021). Physiological study of Flo11 and the particular role of amyloid core sequence. Elife (in revision)

Thematic 2: Functional genomics and heterogeneity

  1. Hassan, H., Goma, G & François J. (2015). The influence of carbon/nitrogen ratio on red pigment and citrinin production by filamentous fungi Monascus ruber is dependent on the cultivation mode. Journal Food Science & Technology. DOI: 10.1111/ijfs.12803
  2. LLanos A, François JM, Parrou JL (2015). Tracking the best reference genes for RT-qPCR data normalisation in filamentous fungi. BMC genomics, 16: 71
  3. Liu, J., Martin-Yken, H., Bigey, F., Dequin, S., Francois, J. & Capp, JP (2015) Natural yeast promoter variants exhibit different noise levels conferring distinct selective advantages. Genome Biol Evol., 7 (4) 969 -984.
  4. Grondin, E., Cheong Sing, A.S., Caro, Y., Raheminadimbny, M., Randrianierenana, A., James, S., Nueno-Palop, C., François J. & Petit, T (2015). A comparative study on the potential of epiphytic yeasts isolated from tropicla fruits to produce flavoring compounds. Int J Food Microbiol. 203, 101 -108.
  5. Liu, J., François, J & Capp, JC (2016) Use of gene expression as experimental parameters to test phenotypic effects. Yeast, 33 209-216
  6. Grondin, E., Shum Cheong Sing, A., Caroa, Y., James, S., Nueno-Palop,C., François, JM.& Petit, T (2017) Flavour production by Saprochaete and Geotrichum yeasts and their close relatives. Food Chem. 237: 677-684.
  7. Turanlı-Yıldız, B., Benbadis, L., Alkım, C., Sezgin, T., Aksit, A., Gökçe, A., Öztürk,Y., Tarık Baykal, A., Çakar, Z.P. and François J M (2017) In vivo evolutionary engineering for ethanol-tolerance of Saccharomyces cerevisiae haploid cells triggers diploidization. J Biosci. Bioeng. https://doi.org/10.1016/j.jbiosc.2017.04.012
  8. Yang , De Billerberck, G., Zhang J-J , Rosenzweig, F. & François, J M. (2017) Deciphering the origin, evolutionary fate and the physiological function of the subtelomeric multi-aryl-alcohol dehydrogenases encoded genes family in the yeast Saccharomyces cerevisiae. Applied Env. Microbiol DOI.org/ 10.1128/AEM.01553.17
  9. Chuppa-Tostain, G., Hoarau, J., Watson, M., Adelard, L., Cheong Sing, A., Caro, Y., Grondin, I., Bourven, I., Francois, J.M., Girbal-Neuhauser, E. & Petit T. (2018) Production of Aspergillus niger biomass on sugarcan distillery wastemwater: physiological aspects and potential for biodiesel production. Fungal Biol. Biotechnol., 5: 1 org/10.1186/s40694-018-0045-6
  10. Jian, L., François, J. & Capp, JP (2018) Bimodality of gene expression from yeast promoter can be instigated by DNA context, inducing condition and strain background. FEMS Yeast Res., 18 (4). doi: 10.1093/femsyr/foy047.
  11. Jian, L. Lestrade, D., Cescut, J. François, J & Capp, JP (2018) A GRX1 promoter variant confers constitutive noisy bimodal expression that increases oxidtaive stress resistance in yeast. Frontiers in Microbiology, 9, 2158. DOI 10.3384/fmicb.2018.02158
  12. Lopez, R.V., Gomez, J.L., Spina, L., Dejean, S., Parrou, JL & François, J M. (2018). Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae. Microbial Cell 5, 444-459. DOI: 10.15698/mic2018.10.651
  13. Llanos, A., Dejean, S., Neugnot-Roux, V., François, J.M. & Parrou, JL (2019) Carbon sources and XlnR—dependent transcriptional landscape of CAZymes in the industrial fungus Talaromyces versatilis: when exception seems to be the rule. Microbial Cell Fact.org/10.1186/s12934-019-1062-8
  14. Deshors, M., Guais, O., Neugnot-Roux, V., Cameleyre, X., Fillaudeau, L., Francois, J.M. (2019). Enzymatic deconstruction mechanism of complex polysaccharides in wheat revealed by combined in situ physical and ex-situ biochemical studies. Bioeng. Biotechnol. 7: 158, doi: 10.3389/fbioe.2019.00158
  15. Jian, L., François, J. M & Capp, JP (2019) Gene expression noise produces cell-to-cell heterogeneity in eukaryotic homologous recombination rate. Genet. 10, 475, DOI : 10.3389/fgene.2019.00475
  16. Cox, N., Kuemmerle, R., Millard, P., Cahoreau, E., François, J.M., Parrou, J.L. & Lippens, G. (2019). An integrated pH meter during reaction monoitoring with dual reception 1H, 31P NMR spectroscopy. Chem. 91, 3959 -3963.
  17. Paloque, L., Père-Berezo, T., Abot, A., Dalloux-Chioccioli, J., Bourgeade-Delmas, S. ? Le Faouder, P., Pijo, J., Teste, MA., Francois, J., Helge Schebb, N, Mainka, M., Rolland, C., Blanpied, C., Dietrich, G., Bretrand-Michel, J., Deraison, C., Valentin, A. & Cenas. (2019) Polyinsaturate fatty metabolites : biosynthesis in Leishmania and role in parasite/host invasion. J. lipid Res., 60, 2019, DOI 10.1194/jlr.M091736.
  18. Liu, J., Mosser, L., Botanch, C., François, J.M & Capp JP (2020) SIR2 expression nois can generate heterogeneity in viability but does not affect cell-to-cell epigenetic silencing at subtelomeric URA3 in yeast. G3, 10, 3435 doi: 10.1534/g3.120.401589
  19. Chuppa-Tostain, G., Tan, M., Shum-Cheong Sing, A., Adelard, L., François, J., Caro, Y. & Petit Thomas (2020). Evaluation of filamentous fungi and yeast for the biodegradation of sugarcane distillery wasterwater. Microorganisms, 8: 1588 doi: 10.339/microorganisms8101588
  20. Arabaciyan, S., Saint-Antoine, M., Maugis-Rabusseau, C., François, J., Singh, A., Parrou, JL & Capp, JP (2021) Insight on the control of yeast single-cell growth variability by members of the trehalose phosphate synthase (TPS) complex. Cell Dev. Biol ., 9, 607628 ; DOI 10.3389/fcell.2021.607628
  21. Tan, M., Caro, Y., Shum-Cheiong-Sing, A., Robert, L., François, J. & Petit Thomas (2020) Evaluation of mixed-fermentation of Saccharomyces cerevisiae with Saprochete swaveolens to produce natural fruity beer from industrial wort. Food Chem 2021 Jan 5;346:128804. doi: 10.1016/j.foodchem.2020.128804

Thematic 3: Refactoring microbial metabolism

  1. Cam, Y., Alkim, C., Trichez, D., Vax, A., Bartolo, F., Besse, Ph., François J & Walther, T (2015) Engineering of a synthetic metabolic pathway for the assimilation of (D)-xylose into added-value chemical. ACS Synthetic Biology, 5, 607-618. DOI10.1021.acssynbio.5b00103
  2. Alkim, C., Cam, Y., Trichez, D., Auriol, C., Vax, A., Spina, L., Bartolo, F., Besse, P., François, J & Walther, T (2015). Optimisation of ethylene glycol production from (D) xylose via a synthetic pathway implemented in Escherichia coli. Cell Fact. 14 :127 DOI 10.1186/s12934-015-0312-7
  3. Alkim, C., Trichez, D., Cam, Y., François, J & Walther, T (2016). The synthetic xylulose 1-phosphate pathway increases production of glycolic acid from xylose-rich sugar mixtures. BMC Biotechnol. Biofuels, 9:201
  4. Walther, Th & François, J (2016) Microbial production of propanol. Biotechnol Adv., 34: 984-996
  5. Walther Th., Topham, C.M., Irague, R., Auriol, C., Baylac, A., Cordier, H., Dressaire, C., Lozano-Huguet, L., Tarrat, N., Martineau, N., Stodel, M., Malbert, Y., Maestracci, M., Huet, R., André, I., Remaud-Siméon, M & François J M. (2017) Construction of a synthetic metabolic pathway for biosynthesis of the non-natural methionine precursor 2,4-dihydroxybutyric acid. Nature Comm., 8, 15828 doi:10.1038/ncomms15828.
  6. Walther, T., Calvayrac F., Malbert, Y., Alkim, C., Dressaire, C., Cordier, H., and Francois, J.M (2018) Construction of a synthetic pathway for the production of 2,4-dihydroxybutyric acid from homoserine. Eng 45, 237-245 DOI/10.1016/j.ymben.2017.12.005
  7. Irague, R., Topham, C., Martineau N, Baylac A, , Stodel M., Auriol C., Walther,Th., François Jean M., ,André I. & Remaud-Siméon M. (2018) Conversion of an aspartate kinase into a malate kinase using a generic HTS assay for kinase screening. PlosOne 13 (2) e0193036
  8. Trichez, D., Auriol, C., Baylac, A., Irague, R., Dressaire, C., Carnicer-Heras, M., Heux, S., François, JM & Walther, T (2018). Engineering of Escherichia coli for Krebs cycle dependent production of malic acid. Microbial Cell Fact.17: 113, DOI: 10.1186/s12934-018-0959-y
  9. Frazao C.R, Maton, V., Walther, T. & François J.M (2018) Development of a metabolite sensor for high-throughput detection of aldehydes in Escherichia coli. Front. Bioeng Biotechnol, section Synth. Biol., 6: 118, DOI:3389/fbioe.2018.00118
  10. Frazao C.R., Topham, C., Malbert, Y., François, J.M. & Walther, T. (2018). Rational engineering of a malate dehydrogenase for microbial production of 2,4 dihydroxybutyric acid production via homoserine pathway. J. 475: 3887-3901. DOI: 10.1042/BCJ20180765
  11. Frazao, C.R; Trichez, D., Spina, L., Lozano-Huguet, L., Serrano-Bataillé, H., Dagkesamankaya, A., Topham, C., Walther, T & Francois, J. (2019). Construction of a synthetic pathway for the production of 1,3-propanediol from glucose. Rep 9: 11576. DOI/ 10.1038/s41598-019-48091-7
  12. Lachaux C., Frazao, C.R., Morin, N., Walther, T & François J.M. (2019) Design, construction and validation of a synthetic pathway for glycolic acid production from lignocellulosic sugars with optimal carbon conservation. Bioeng Biotech., 7, 359. DOI: 10.3389/fbioe.2019.00359
  13. François J.M., Lachaux, C. & Morin Nicolas (2019). Synthetic biology applied to carbon conserving pathways: a mini-review. Bioeng Biotech.7: 446; DOI 10.3389/fbioe.2019.00446
  14. François J., Alkim, C & Morin, N. (2020). Engineering microbial pathways for production of bio-based chemicals from lignocellulosic sugars: Current status and perspectives. BMC Biotechnology for Biofuels. 13:118. DOI : 10.1186/s13068-020-01744-6

 

Patents since 2012

  1. Walther, T., Cordiez, H., Topham Ch., Andre I, Remaud-Simeon, M., Huet, R. & François, J. A novel method of production of 2,4-dihydroxybutyric. Submitted October 27th 2011 PCT/FR2011/000578, published May 5th 2012 as WO2012/056318A1, granted January 19, 2016 as US 9,238,829 B2
  2. Walther, T., Cordier, H., Dressaire, C. François, J. A production of 2,4-dihydroxybutyric by malyl-CoA pathway. Submitted on April 25th 2012 as PCT/FR 2012/001071 and published October 31th as WO2013/160762A2
  3. Walther, T., Dressaire, C., Cordier, H. & François, J. “A method for preparation of 2,4 dihydroxybutyric acid”. Patent deposition PCT/EP 2013/064619 on 10 July 2013; Priority: brevet US patent July 12th n°61/670,405, published January 16th 2014 as WO2014009435 A1
  4. Walther, T., François, J. "A microorganism modified for the production of 1,3-propanediol". Patent deposition n° PCT/EP 2013/064616 on 10 July 2013, Priority US onJuly 12th, n° 61/670 389, published January, 16th 2014 as WO2014009432 A1
  5. Senescau, A., François, J., Bernier, M. & Fabre, R (2013) « Biopuce pour la détection et identification de bactéries du genre légionella, kit et procédé d’utilisation ». Patent published 21th March 2014 as EP2995614
  6. Foncy, J., Trevisiol, E., Severac, C., François, J. (2014) Procédé d’immobilisation d’un composé d’interêt sur un support selon un motif donné et kit pour sa mise en œuvre. Dépôt français n° FR °14 60398 le 29 octobre 2014, extension PCT3368899, US2018/0311635 A1, CN108337902A, 2018
  7. Walther, T., Cam, Y & François J (2014) Procédé de production d’au moins un métabolite d’intérêt par transformation d’un pentose dans un microorganisme. Demande de brevet international déposé par INRA n° FR14 61183 du 18 nov 2014 ; WO2016/079440 A1, 26 mai 2015
  8. Lachaux C., Walther, T & François J. Microorganismes et procédé pour la production d’acide glycolique à partir de pentoses et d’hexoses. Demande de déposition n° FR1856511 13/07/2018, published 17 January 2020 as WO 2020/012138 A1
  9. Francois, JM (2019), Microorganismes et procédé pour la production de molécules d’intérêt à partir de pentoses et hexoses. Déclaration d’invention DI-RV-18-0128 auprès de INRA transfert 12 mars 2019
  10. KOCH Daniel Johannes, PARIZZI Lucas Pedersen, GALZERANI Felipe, FRANCOIS Jean Marie and LAJUS Sophie (2020): DEGRADATION PATHWAY FOR PENTOSE AND HEXOSE SUGARS U.S. Patent Application No. 16/796,426 and PCT/BR2020/050053 Data filed: February 20, 2020 and published 20th August 2020 as WO202/168408
  11. KOCH Daniel Johannes, ALEXANDRINO Paulo, GALZERANI Felipe, FRANCOIS Jean Marie and MORIN Nicolas (2020) MICROORGANISMS AND METHODS FOR THE PRODUCTION OF GLYCOLIC ACID AND GLYCINE VIA REVERSE GLYOXYLATE SHUNT. U.S. Patent Application No. 16/791,556 and PCT/BR2020/050041 Data filed February 14, 2020. Published 20th August 2020 as WO 2020/163935 A1

 

 

OTHERS

2010 : Co-founder of the company 'Dendris' aiming to exploit the Bionanotechnolopgies for in vitro molecular diagnostics (third generation diagnostics) based on biochips functionalized by dendrimer chemistry.