Enzymology & Metabolism Group

The Enzymology & Metabolism group at the LCSB

From left to right: Corey Griffith, Marat Kasakin, Myrto Patraskaki, Christian Jäger, Dean Cheung, Jean-François Conrotte, Ursula Heins-Marroquin, Adhish Walvekar, Carole Linster (Principal Investigator), Florianne Vanhalle, Xiangyi Dong, Edward Kim Nguyen

About the Enzymology & Metabolism Group A major objective of our group is to exploit genomic and post-genomic data to discover new enzyme functions, to reduce the number of orphan enzymes, and to fill gaps in metabolic networks. Priority is given to putative enzymes conserved in humans and potentially linked to disease or aging. Several observations clearly indicate that our understanding of cellular metabolism, and the regulation thereof, is far from being complete. First, inspection of the constantly increasing number of sequenced genomes reveals that, for a majority of organisms, more than half of the genes remain without identified function. Second, metabolomics studies show that the metabolome of many organisms is much larger than anticipated based on the currently known metabolic pathways. Third, the observation that many genes of unknown function belong to widely conserved families indicates that a significant portion of them encode enzymes. Also, recent studies by us and others suggest that enzymatic repair reactions play a much more important role in the maintenance of a functional proteome and a healthy cellular metabolism than previously thought.

Our research currently focuses on better understanding the physiological functions of recently identified protein and metabolite repair mechanisms and on developing strategies for accelerating enzyme function discovery. Comparative genomics-based bioinformatic tools are used for in silico predictions of gene functions. Liquid chromatography and mass spectrometry-based metabolomics methodologies and the model organism Saccharomyces cerevisiae are central tools used in our research for experimental predictions and validations of gene functions. Follow-up studies in human cell lines are performed for investigating the function of human orthologs of genes of interest by using RNA interference and overexpression techniques. Production of recombinant proteins, protein purification and the set-up of enzymatic assays are also important methodologies used by the group for biochemical validation of predicted gene functions and characterization thereof.Our research is intended to impact fields ranging from medicine to metabolic modeling and metabolic engineering.