Physiology and Microbial Metabolism

 

 

Group leader: Jean-Marie François (INSA Professor)

The group Physiology and Microbial Metabolism is organised around two advanced technology platforms (Biochips and Metabolome-Fluxome) and four research teams:

 

  •  Team: Metabolic Engineering and In Vivo Molecular Evolution of Prokaryotes

Team Leader: Isabelle Meynial-Salles (Assistant Professor)

 

  •  Team: Metabolic Analysis of Procaryotes

  Team Leader: Pascal Loubière (INRA Research Director)

 

  •  Team: Molecular Physiology of Eukaryotes

  Team Leader: Jean-Marie François (INSA Professor)

 

  • Team: Integrated Metabolism and Dynamics of Metabolic Systems

 Team Leader: Jean-Charles Portais –UPS Professor)

 

The group is made up of complimentary approaches, including:

 

  •  functionality and topology of biochemical network
  •  quantification of metabolic fluxes using isotopic tracer analysis
  •  mechanistic modelling of metabolism based upon enzyme kinetics and metabolite pool quantification
  •  enzyme structure-function relationships
  •  genetic regulation of metabolic networks using post-genomic tools
  •  molecular evolution of micro-organisms
  •  metabolic engineering to modify rationally carbon and energy fluxes so as to improve the catalytic potential of micro-organisms.

 

All the research is oriented towards obtaining a systemic understanding of the microbe, to better understand its functional basis but also with a view to modifications of the genome so as to improve the response of the organism to extreme process-related constraints, during metabolite over-production. If this often implies pure cultures of specific micro-organisms, this approach is increasingly being applied to mixed populations.

 

Each EAD follows its own scientific objectives; frequently in synergy with EADs from other groups and with teams from outside the laboratory, but there is also a strong commitment to regroup the different levels of expertise available around projects of high impact. This is achieved for a certain number of key projects involving three model organisms, the yeast S. cerevisiae and the bacteria E. coli and L. lactis. Global understanding of these organisms is being pursued via i) establishing the specific changes in gene expression in response to specific stimuli, ii) analysis of the consequences of such modifications on carbon flux within the metabolic network, iii) analysis of whole genome compensatory mechanisms, and iv) the initiation of a new in silico modelling activity.

 

 

These fundamental studies aimed at establishing baseline knowledge in integrated microbiology are completed by more applied aspects of metabolic engineering to exploit the capacity of microbes to produce a variety of small molecules. This is particularly so in the domain of white biotechnology linked to sustained development for bulk and commodity chemical production as well as more specific applications in the food and health sectors.

 

Over the last few years, a number of new projects have been initiated to reply to the increasingly important demand of society as regards the metabolic phenomena which are stimulating the expression of virulence in certain pathogenic bacteria, notably those involved in the food chain. Understanding how specific virulence factors are induced in response to nutritional perturbations or stress situations and the metabolic phenomena leading to such phenotypes is being established using the same molecular toolbox as is used for other applications. This approach is opening up new inroads to understand how pathogens have developed, with possible new therapeutic opportunities being established.

 

 

Key words:

Metabolism, regulation, metabolic engineering, transcriptome, fluxome, integrated biology.