Thesis Project

Defining organellar metabolites using next-generation CRISPR screens

Maintaining metabolic homeostasis is a fundamental necessity for all living organisms. In humans slight deviations in metabolite concentrations can be disastrous resulting in major human pathologies such as cancer. As a result, cells dedicate significant resources to maintain and regulate biochemical pathways to provide a steady supply of energy and building blocks. Key to this metabolic control are intricate signal transduction pathways that sense changes in metabolite concentrations and execute transcriptional programs to rapidly restore them. While much progress has been made in the last century to catalog the substrates, products, intermediates and the enzymes required to undertake different biochemical reactions, we still lack a sophisticated understanding for how many metabolites are sensed, how the corresponding pathways are wired, how these pathways adapt to changes in the cellular nutrient environment.

Succinate biosensor

Genetically encoded biosensors have revolutionized our understanding of dynamic changes in metabolic states in cancer cells. How metabolites are regulated within distinct cellular compartments remains poorly understood. The focus of this project will be to identify the genes and pathways that sense and regulate different organellar metabolites using biosensors and CRISPR screens. Using advanced cell biological techniques, students will establish reporter cell lines localizing biosensors to different organelles and then undertaking whole-genome CRISPR loss of function screens and small molecule screens to identify genes involved in the regulation of metabolite levels. Cellular and biochemical characterization will be undertaken to identify the precise mechanisms by which organellar metabolites are sensed.

We are looking for a motivated student with a background in biochemistry and cell biology or a relevant field to support our efforts in advancing this exciting project. The applicant will be directly supervised by the research director of the laboratory (Prof. Bar-Peled) and will gain experience in next-generation functional genomic screens, high-throughput technologies, and mechanistic biochemistry analysis.

The successful candidate will be potentially also invited to pursue their PhD project to finalize the project in form of a publication. 

We offer a world renown learning environment, state-of-the-art facilities and guidance by experienced researches in the scientific hub of the United States. 

If interested, please send your CV, a cover letter describing your motivation and a letter of recommendation. 

Location: Bar-Peled lab, Massachusetts General Hospital Cancer Center/Harvard Medical School
Start: Summer/Fall 2021
Duration: >6 months

Prof. Dr. Liron Bar-Peled
Cancer Center
Massachusetts General Hospital
Harvard Medical School Departement of Medicine

Tel: 617-519-6531 Fax: 617-724-6919

Building 149, Thirteenth Street
Charlestown, Massachusetts 02129