DC6

Background:  Cancers have an altered metabolism. This altered metabolism can be leveraged for the identification of cancer-specific vulnerabilities. The proof-of-concept has been made for NAD metabolism with synthesis inhibitors showing efficacy in some preclinical cancer models.

Objectives: (1) Analyze the expression of and the dependency on metabolic enzymes in cancer samples and cell lines, with a particular focus on enzymes located in the nucleus. (2) Determine genetic and pharmacologic perturbations of nuclear NAD levels in cultured cancer cells. (3) Determine the impact of these perturbations on gene expression and chromatin structure.

Location and research group:

This project will be jointly supervised by Marcus Buschbeck and Tanya Vavouri at the headquarters of the Josep Carreras Leukaemia Research Institute (Badalona, Barcelona, Spain). The successful Doctoral Candidate will have strong analytical skills (bioinformatics, stats, maths) and will be highly motivated to carry out fundamental research on this project that combines genomics, gene regulation, metabolism and cancer.

The Buschbeck lab performs both basic and applied research. In our basic research, we aim to understand the molecular mechanism by which histone variants link epigenetic regulation to metabolism and nuclear organization. In our translational research, we mine the chromatin regulatory space for combinatorial drug targets that can improve the therapy of blood cancers. The Vavouri lab uses genomics and bioinformatics tools to understand the effect of the environment and mutations on gene and genome regulation.