Project

Exploiting the unique biology of the protozoan parasite Leishmania as a model system, the ERC project DECOLeishRN will generate unprecedented insight into the role of genome instability in eukaryotic adaptation by combining experimental evolution, analyses of the non-coding RNA, network modelling and cutting-edge, single cell sequencing. The project aims to uncover the molecular filter that can mitigate toxic effects of genome instability while promoting beneficial ones, thus resolving a long-standing question in infection and cancer biology. We expect to reveal complex and dynamic interactions between genomic, epitranscriptomic and phenotypic adaptation of these important parasites that compensate for detrimental gene dosage changes. The study of pathogen evolution in culture and within a mammalian host will provide an innovative framework for the discovery of complex biomarker candidates linked to Leishmania virulence and drug resistance. Exploiting genome instability for adaptation is common to other diseases-causing microbes and cancer. This project will thus deliver a blueprint to study how chaotic genome instability is harnessed for adaptation and to escape unfavorable environmental conditions.