Temporary scientific engineer / Scientific computing / Computational Biology / Graduate degree or equivalent

Assignments:
The recruited person will be taken to carry the softwaredevelopment related to themetabolic-modelling part of the SLIMMEST project.

The dynamics of a microbial community is driven by the metabolism of its microorganisms, the interactions between those microorganisms, and spatio-temporal interactions between them and the environment. Mathematical and computational models of such dynamics are crucial to build mechanistic hypotheses of the biological observations, as well as predict the evolution of the ecosystems, and actions to lead ecosystems in a desired state. SLIMMEST will combine logic programming and metamodelling of metabolism in a scalable framework applied to communities of the gut microbiota.

The mission of this engineering position is to develop methods suitable to the reduction of metabolic models for a community. The purpose is to simplify the metabolism of an ecoystem by targeting crucial functions that are main drivers of the ecosystem. The results will be used in mathematical models by the postdoc scientist of the project.

For that purpose, we must model the metabolism of bacteria from their genome, and connect metabolic networks to the available literature resources on pathways of interest such as short-chain fatty acid production. The simplification of the community metabolism will be performed by modelling constraints and solving combinatorial optimisation problems. In addition, the successful candidate will contextualise the results of community metamodelling back to metabolic networks. The first application of the project will be a model of the murine gut microbiota, with expectations to successfully scale up the size of the community during the project.

For a better knowledge of the proposed research subject:

• J. D. Orth, I. Thiele, and B. Ø. Palsson, « What is flux balance analysis? ». In : Nat Biotechnol, vol. 28, no. 3, pp. 245–248, 2010, doi: 10.1038/nbt.1614.

• Arnaud Belcour et al. « Metage2Metabo, microbiota-scale metabolic complementarity for the identication of key species ». In : eLife 9 (2020), e61968. doi : 10.7554/elife.61968.
• Seth R Bordenstein et Kevin R Theis. « Host biology in light of the microbiome : ten principles of holobionts and hologenomes ». In : PLoS Biol 13.8 (2015), e1002226.
• Oliver Ebenhöh, Thomas Handorf et Reinhart Heinrich. « Struc- tural analysis of expanding metabolic networks. » In : Genome informatics. International Conference on Genome Informatics 15.1 (2004), p. 35-45. issn : 0919-9454.
• Clémence Frioux, Simon M Dittami et Anne Siegel. « Using automated reasoning to explore the metabolism of unconventional organisms : a first step to explore host–microbial interactions ». In : Biochemical Society Transactions 48.3 (2020), p. 901-913. issn : 0300-5127. doi : 10.1042/bst20190667.
• Simon Labarthe et al. « A mathematical model to investigate the key drivers of the biogeography of the colon microbiota ». In : Journal of theoretical biology 462 (2019), p. 552-581.
• Ilias Lagkouvardos et al. « The Mouse Intestinal Bacterial Col- lection (miBC) provides host-specific insight into cultured diversity and functional potential of the gut microbiota ». In : Nature microbiology 1.10 (2016), p. 1-15.
• Arun S Moorthy et al. « A spatially continuous model of carbohydrate digestion and transport processes in the colon ». In : PloS one 10.12 (2015), e0145309.
• Alberto Noronha et al. « The Virtual Metabolic Human database : integrating human and gut microbiome metabolism with nutrition and disease ». In : Nucleic Acids Research 47.D1 (2018), p. D614- D624. issn : 0305-1048. doi : 10.1093/nar/gky992.
• Clémence Frioux et al. « Scalable and exhaustive screening of metabolic functions carried out by microbial consortia ». In : Bioinfor- matics 34.17 (2018), p. i934-i943. issn : 1367-4803. doi : 10.1093/ bioinformatics/bty588.

Collaboration :

The recruited candidate will mainly collaborate with the two permanent researchers and the postdoc associated to the SLIMMEST project. He or she will also collaborate with the other members of the team.