Apr 8, 2019
Interview with new group leader Guillaume Diss
|All group news|
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.
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Domingo J, Diss G and Lehner B (2018) Pairwise and higher order genetic interactions during the evolution of a tRNANature. 558:117-121
Diss G and Lehner B. (2018) The genetic landscape of a physical interactioneLife. 7:e32472
Diss G, Gagnon-Arsenault I, Dion-Coté AM, Vignaud H, Ascencio DI, Berger CM, Landry CR. (2017) Gene duplication can impart fragility, not robustness, in the yeast protein interaction networkScience. 355:630-634
Filteau M*, Diss G*, Torres-Quiroz F et al. (2015) Systematic identification of signal integration by Protein Kinase AProc Nat Acad Sci. 112:4501-6.
Diss G, Ascencio D, Deluna A, Landry CR. (2014) Molecular mechanisms of paralogous compensation and the robustness of cellular networksJ Exp Zool B Mol Dev Evol. 322:488-99
Diss G, Dubé AK, Boutin J, Gagnon-Arsenault I, Landry CR. (2013) A systematic approach for the genetic dissection of protein complexes in living cellsCell Reports. 3(6):2155-67
Diss G*, Filteau M*, Freschi L*, Leducq JB*, Rochette S*, Torres-Quiroz F*, Landry CR. (2013) Integrative avenues for exploring the dynamics and evolution of protein interaction networksCurr Op Biotechnol. 24(4):775-83
Full list of publications
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