Post-doc presso l'università degli Studi di Milano
- 27 Sep 2018
Exploiting the CRISPR-Cas9 technology to study the double strand DNA break repair and genome stability.
Department of Biosciences, University of Milan.
Beginning and duration: January-June 2019– 1 year, renewable.
Description: The ability of cells to detect and properly repair double stranded DNA breaks (DSBs) is essential for maintaining genome stability and preventing cancer development. Indeed, DSBs are the most cytotoxic forms of DNA damage, because inaccurate DSB repair leads to mutations and/or gross chromosomal rearrangements. A critical step in regulating DSB repair is the processing of its DNA ends. Several factors are involved in this mechanism, which are conserved in all eukaryotes. Mutations in most of these factors lead to genome instability, cancer and severe human inherited diseases.
Initially, the project will start in model organism S. cerevisiae and it will be focused on the characterization of critical factors and mechanisms involved in the processing and repair of Cas9-induced DSB. Indeed, it is an open debate in the literature whether the Cas9-induced DSBs are processed through the classical DSB repair pathways and factors or they are processed by different specialized mechanisms.
Recently, we developed a PCR-based method to precisely quantify Cas9-induced DSB in yeast and human genome (https://doi.org/10.1016/j.dnarep.2018.06.005), which will be of great utility in this project.
Depending upon the results, the project will be extended to human cell lines with the aim to verify the possible conservation of the factors and mechanisms previously obtained in yeast.
Requirements: Good theoretical knowledge and possibly practical experience in genetics, biochemistry, molecular and cell biology. Experience in yeast cell culturing and manipulation. Previous experience with DNA damage response and cell cycle is a plus. High motivation and dedication. Good knowledge of English.
Reference letters required.
Achille Pellicioli, PhD