Job description:
The demand for amino acids for protein synthesis, nucleotide, and energy production, is very high in the growing tumor. The metabolic changes a tumor undergoes to adapt to deregulated growth represent vulnerabilities that can be exploited for therapy. This was successfully demonstrated in past years for the amino acid asparagine, resulting in a very effective combined treatment of chemotherapy and L-asparaginase in acute lymphoblastic leukemia (ALL). To exploit metabolic vulnerabilities related to amino acids one needs to overcome the major obstacle of identifying which amino acid is restrictive to the tumor. We recently developed a novel measurement approach that senses restrictive amino acid in cells. We named it diricore (differential ribosome codon reading), and it is based on the ribosome profiling technology (Loayza-Puch F. et al, Nature. 2016). The main goal of this project is to uncover novel deficiencies in amino acid availabilities in response to mitotic inhibition using the diricore platform and exploit them for better cancer killing. Following diricore analysis, we will setup experiments to elucidate relevant metabolic pathways using genetic and biochemical tools, such as CRISPR-Cas9 knockouts, RNAi knockdowns, and overexpression vectors. The identified amino acid shortages and their links to changes in metabolic genes will serve as signatures for diagnosis and guideline for therapy. Moreover, our findings will offer ways to make the treatment of aggressive tumors more effective.
This project is a collaboration between the laboratories of Dr. Fabricio Loayza-Puch at the DKFZ and Ayelet Erez at the Weizmann Institute of Science in Rehovot, Israel. The successful candidate will spend approximately 3-6 months of the project conducting research in Israel (this may be split into multiple visits).
The project is funded by the German-Israeli Helmholtz Research School in Cancer Biology, a joint PhD training initiative of the German Cancer Research Center in Heidelberg and the Weizmann Institute of Science in Rehovot, Israel. The successful candidate will become a member of the Research School and benefit from joint mentoring of the collaborating scientists, additional joint networking meetings and training opportunities.
For further information about the Research School, please visit the website https://www.dkfz.de/en/phd-program/GIHRS.html.