Guillaume Diss

Quantitative and mechanistic models of genotype-phenotype maps

Our research focuses on understanding the mechanisms through which genetic variation translates into phenotypic variation, e.g. diseases or functional innovations. A cell is an ensemble of molecules that interact together and form a complex network of molecular interactions. This network organizes biological processes and cellular functions and determines the phenotype of the cell. Mutations quantitatively perturb the way proteins interact with each other and with other molecules. This in turn perturbs the architecture of the network and the complex and dynamic equilibrium between biological processes, which can result in a phenotypic change.

We will combine quantitative genetics, biochemistry and systems biology approach together with modeling and computational biology to develop quantitative and mechanistic models of mutation effects. We will measure the effects of mutations at different levels of organization, from single genes (expression, protein stability, enzymatic activity) to molecular interactions (protein-protein, protein-nucleic acids) and network architecture. We will then use this data to generate our models. Strong focus will be placed on understanding the mechanisms through which the effects of mutations depend upon additional genetic variation (i.e. epistasis), uncovering the general principles of biological organization and of its evolution.

Guillaume Diss
Isabella Bogdal
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