About her PhD project

Rare diseases are mostly due to mutations in a single gene that lead to a strong phenotypic impact. However, the dogma “one mutation in one gene - one disease” is too simplistic: heterogeneities are a hallmark of monogenic diseases. These heterogeneities can be extensive as, for instance, the same mutation in the dysferlin gene (DYSF) can cause either proximal or distal muscular dystrophies. These heterogeneities remain largely unexplained and we aim at better understanding this complex genotype-phenotype relationship through the study of the regulatory networks in which disease genes are involved. The project proposes to build a logical model of DYSF cellular processes, while developing new mathematical tools to address dynamical behaviors and heterogeneities specific to these diseases. Indeed, while most biological networks display stability (in the sense that they are able to maintain the reachability of expected phenotypes), in the context of rare diseases this stability seems to be significantly impacted. We will take advantage of the DYSF logical model and logical tools to address the question of observed heterogeneity.