Metabolism of Genome Regulation during Brain Development
Summary
DNA replication, histone modification and transcription all have specific metabolic requirements. These may provide a direct link between gene expression and the metabolic status of the cell, tissue or organism. The objective of this project is to uncover how metabolic enzymes contribute to regulation of gene expression.
Project aims
You will identify metabolic enzymes that show dynamic nuclear localisation, study whether they associate directly with the DNA, and profile the cell-type specific genome-wide impact of metabolic changes on transcription and histone modifications in vivo. We will use single-molecule and FRAP imaging approaches to quantify intranuclear protein dynamics, and take advantage of genetically encoded metabolite sensors to study nucleus/cytoplasm metabolite ratios, in vivo in the Drosophila brain and large nuclei of the salivary gland. Finally, we will determine how these enzymes are affected by acute and chronic mitochondrial dysfunction.
The project will rely mostly on various confocal live imaging modalities, CRISPR/Cas9-mediated genome editing and novel cell-type specific in vivo chromatin profiling technology based on Targeted DamID-seq. Basic knowledge of bioinformatic pipelines to analyse NGS-datasets is a plus, but the student will receive further bioinformatics training during the project.
Contact details
Dr Jelle van den Ameele (jv361@cam.ac.uk) Neurology and Mitochondrial Biology Unit
Opportunities
This project is open to applicants who want to do a:
- PhD
- MPhil