M2 - Protein families of unknown function in glycan-breakdown operons : identifying genomic constraints and predict enzymatic substrates

Context

Glycan breakdown is central to human and animal nutrition, fungal/algal/plant-cell wall remodelling, biomass re-utilization, host-pathogen interactions, etc.

The Glycogenomics team at AFMB is maintaining for 30 years the reference classification of Carbohydrate-Active enzyme (CAZy) protein families involved in glycan breakdown. Family creation in CAZy has long been a simple reaction to the publication of the biochemical characterization of a protein previously “of unknown function” by independent wet-lab research groups across the globe. Significantly, the number of families has grown steadily while the modern sequencing technologies and multiplicity of (meta-)genomic projects produced an exponential amount of data in the last decades. The Glycogenomics team participated to the analysis of this deluge of data, and the accumulated genomes and CAZy annotation can now be exploited to actively guide future family discoveries.

To do so, we recently obtained an Agence National de la Recherche (ANR) funding, named ODE project, to perform comparative genomics analyses. Guided by the genomic context, protein families of unknown function will be built. Non-enzymatic families will be identified based on their physical constraint/genomic position. Meanwhile, for the most likely to be carbohydrate-active enzymes, the substrate category will be predicted using the known specificities of their co-occurring partners. These predictions will be validated through wet-lab experiments by our collaborators. As a consequence, the Glycogenomics team is looking for a talented Master student with a solid curriculum and ambition to pursue this work in the future in our team, as an engineer or a PhD candidate.

Expected skills

Protein sequence analysis (Blast/MAFFT/HMMER/HHsuite)
Comparative Genomics (Analysis of GFF, SQL)

Related literature

Bacteroidetes use thousands of enzyme combinations to break down glycans (2019)
Lapebie P, Lombard V, Drula E, Terrapon N, Henrissat B.
Nat Commun 10 2043 PMID:31053724