Topic "Understanding metabolic & regulatory netwoks"
A few words
Understanding metabolic & regulatory networks of microorganisms
In this topic, the objective is to understand how microorganisms (i.e. E. coli, B. methanolicus, P. pastoris) develop integrated metabolic responses to changes in their environment or with respect to acquired novel functions. Typically, such a response involves complex regulatory mechanisms, and our objective is to precisely understand how natural (or synthetic!) metabolic & regulatory networks cooperate in the integrated response of the cell. We then exploit this knowledge to upgrade the designability of industrially useful microorganisms (See Topics 2).
Metabolism regulation in E. coli by post-translational modifications: Acetyl-phosphate (AcP) is an intermediate of the acetate pathway but it can also modify proteins by phosphorylation or acetylation. Protein acetylation in bacteria occurs through the action of acetyltransferase using acetyl-CoA or non-enzymatically by AcP. A large part of the central metabolic enzymes can be acetylated suggesting a role of acetylation in metabolism regulation. This research project aims to understand how AcP controls bacterial metabolism via protein acetylation by correlating the level of AcP in bacterial cell to the changes of AcP-acetylated protein sites.
Bacteria have long been considered as mere « enzyme pouches », without any real degree of subcellular metabolic organization. This view started evolving with the discovery of bacterial microcompartments (BMCs). BMCs are highly organized proteinaceous structures, made of a semi-permeable shell that encapsulates specifically targeted enzymes. This project aims at characterizing the native Eut BMC system in Escherichia coli to understand i) how the Eut BMCs form, ii) how the Eut BMCs enhance the metabolic properties of the pathway they encapsulate and iii) how to repurpose the native Eut BMCs through a synthetic biology approach.
Acetate is a major by-product of glycolytic microbial metabolism. Acetate diverts carbon out of cellular metabolism and is toxic for the cells, thereby decreasing the productivity of bioprocesses. The origin, control and regulation of acetate production remain to be clarified. In this project, we address fundamental and applied questions on the role and regulation of acetate overflow in E. coli, with the objective to propose strategies to improve production in E. coli based bioprocesses. E. coli, dans le but de proposer des stratégies pour améliorer la productivité des bioprocédés basés sur E. coli.
In this project, we develop a methodology to allow real-time analysis of the dynamics of metabolic systems in cell extracts by NMR, with the objective to set up a platform for rapid screening and optimization of metabolic networks for biotechnological applications.