The European Research Council has awarded a grant of over 9 million euro to Institut Pasteur, Bar Ilan University, and the Weizmann Institute of Sciences for a project that will generate unprecedented insight into the role of genome instability in eukaryotic adaptation by combining experimental evolution, analyses of the non-coding RNome, network modelling and cutting-edge single cell biology.
Exploiting the unique biology of the protozoan parasite Leishmania as a model system, the project will uncover the biological filter that can suppress toxic effects of genome instability while promoting beneficial ones, thus resolving a long-standing question in infection and cancer biology.
This six-year project (2023-2029) applies experimental evolution in vitro and in vivo with the objective to uncover novel mechanisms of Leishmania genomic and epistatic adaptation underlying fitness gain. Dynamic genome and transcriptome changes will be mapped at single cell, clonal, and population levels in Leishmania promastigotes evolving to higher fitness in culture, in the presence of stressors such as anti-leishmanial drugs and in infected animals.
This project is poised to generate unprecedented insight into complex and dynamic interactions between genomic, epitranscriptomic and phenotypic adaptation of these important parasites. At Bar-Ilan university (BIU) we aim to study the role of stress-adapted ribosomes and non-coding RNA especially anti-sense regulators that together constitute a filter for gene expression enabling the expression of beneficial genes and mitigate the toxicity of unwanted amplified genes. The BIU projects will utilize tools from molecular biology (CRISPR knockout), RNA Biology, biochemistry of nucleic acids and RNA-protein complexes, cell and infection biology. Post-doctoral fellows and graduate students are welcome to apply.
The study of pathogen evolution within a mammalian host will provide an innovative framework for the discovery of complex biomarker candidates linked to Leishmania virulence and drug resistance, which will be provide a blueprint for other eukaryotic pathogens of medical importance. Utilization of genome instability for adaptation is common to other infectious diseases and cancer and our studies should provide insight on how the chaotic genome instability is controlled and harnessed for adaptation especially under unfavorable growth conditions.
Contact: Professor Shulamit Michaeli
Mina and Everard Goodman Faculty of Life Sciences Bar-Ilan University, Israel