Nuclear propionyl-CoA as a mediator between nutrition, chromatin regulation and cancer cell proliferation

About the Project

The Babraham Institute is a world-leader in fundamental biological research investigating the systems that underpin development and healthy ageing. It is a recognised postgraduate University Partner Institute of the University of Cambridge. Starting October 2025, a Research Studentship will be available leading to a University of Cambridge PhD degree in the laboratory of Dr Sophie Trefely Sophie Trefely » Babraham Institute. This studentship can be awarded for up to 3 years.

Details of our interactive scientific programmes can be found on www.babraham.ac.uk. As a student at the Institute, you will have access to all of our outstanding science facilities, each one providing specialist equipment and expertise to support key research techniques and technologies. 

Project Details

Chromatin modifications coordinate gene expression to establish cell identity and function and are strongly linked to metabolism since they are formed from specific precursor metabolites in the nucleus. Exciting recent work in the Trefely lab and others have identified distinct metabolic regulation within the nucleus, which is reflected in chromatin modifications. This is groundbreaking because it indicates that the nucleus itself exerts a layer of control connecting cellular metabolism to chromatin regulation. Notably, we detected enrichment of the metabolite propionyl-CoA in the nucleus of a cancer cell line and showed that external nutrients could modify nuclear propionyl-CoA abundance, which correlated with histone lysine propionylation (Kpr). Although Kpr marks are associated with active gene transcription, the role of nuclear propionyl-CoA and Kpr in cancer cells is unknown. This project will test the hypothesis that nuclear propionyl-CoA and other similar metabolites support gene expression in cancer cell proliferation. This project will make a significant contribution to our emergent understanding of metabolic signalling to the nucleus and investigate novel mechanisms sustaining cancer cell proliferation.

The candidate will profile nuclear metabolism following cell division in cancer cell models using state-of-the-art liquid chromatography-high resolution mass spectrometry (LC-HRMS) based subcellular metabolomics approaches developed in the Trefely lab. They will apply nutrient perturbations and genetic manipulation of metabolic enzymes to determine the dynamic range of nuclear propionyl-CoA and other key metabolite concentrations and map the pathways sustaining them. They will test the relationship between nuclear propionyl-CoA concentration and Kpr and other chromatin modifications, gene expression, gene accessibility and cell growth and proliferation. Chromatin modifications will be measured by Western blotting and proteomic approaches. Genomic localisation of chromatin marks and effects on gene expression will be measured by sequencing approaches (CUT&Tag, RNA-sequencing, and ATAC-seq).

This project is part of the NUCLEAR doctoral network on Metabolic Regulation of Genome Function and Cell Identity. The NUCLEAR network incorporates 16 students , 14 beneficiaries and 12 partner organisations across Europe and beyond. Training in subcellular quantitative proteomics will be facilitated by a secondment to the University of Milan and to P4H (Precision for Health) in in Spain analyze data and blood samples to identify factors associated with Pr-CoA levels. As part of this program, the student will participate in network meetings, workshops, training and secondments to build transferrable skills, share findings, build collaborations and maximise impact and kickstart research careers in this exciting emerging field.

Keywords: Nucleus, metabolism, epigenetics, chromatin modification, propionylation, cancer, cell growth. 

How to Apply

·       Information about this project, Project 17, can be found here

·       The application form to apply for this project can be found here

·       Information about the NUCLEAR Network can be found here

The Babraham Institute is a Partner Institute to the University of Cambridge, this means that the successful candidate will need to register to the University of Cambridge and submit an application form via the University’s Graduate Application Portal (Instructions will be sent directly to the successful candidate when required), subsequently you will need to meet the conditions of the University’s Terms of Admission requirements before a full unconditional offer is presented.

If you have any questions not answered on our website about Babraham Institute, doing your PhD with us and training, please contact us: The Graduate Studies Programme Administrator, email [email protected].

Babraham Institute is an equal opportunities employer. An Institute supported by the Biotechnology and Biological Sciences Research Council.