PhD Research Project-A novel role in mitochondrial homeostasis for the anti-ageing factor RBBP5

Details

The mitochondrion has evolved from the endosymbiotic interaction of an alpha-proteobacterium and an archaeon. One major event during this evolution was the transferring of genes from the symbiont to the host. The mitochondrial genome has retained about a dozen of protein coding genes, but about 1000 different proteins form the total mitochondrial proteome. An unbalanced mitochondrial proteome can be catastrophic if not repaired by the mitochondrial stress response. The mitochondrial stress response increases expression of genes that restore and protect the mitochondria. Left uncorrected, the unbalanced proteome will cause premature ageing and death. Therefore, the mitochondrial stress response is critical to maintain mitochondrial homeostasis and prevent premature ageing.

My lab identified RBBP5 as an anti-ageing factor crucial to maintain mitochondrial function. It is also required to induce a specific mitochondrial stress response called the mitochondrial Unfolded Protein Response (mitoUPR). The mitoUPR in C. elegans protects the mitochondria and extends lifespan. RBBP5 is essential for methylation at histone 3 lysine 4 (H3K4). H3K4 methylation is associated with transcriptionally active genes and is an evolutionary conserved epigenetic modification.

Your project will investigate the mechanisms by which RBBP5 prevent ageing. Your experiments will focus on studying mitochondrial homeostasis and the mitoUPR. You will use both C. elegans and cell culture to define the set of genes regulated by RBBP5 at both transcriptional and translational levels. To this end, you will use CRISPR-edited versions of attenuated RBBP5 coupled with deep sequencing such as ChIP-seq and RNA-seq as well as proteomic technologies. Selected versions of RBBP5 will then be investigated in mammalian cell culture and embryonic Stem Cells. In summary, the selected student will be trained in a range of molecular biology, genomic and proteomic approaches to unravel fundamental biological principles central to mitochondrial function and ageing.

Training/techniques to be provided

Approaches used will include C. elegans genetics and transgenesis, mammalian cell culture, mutagenesis, fluorescence microscopy, RNAi, CRISPR gene editing, genomics and proteomics.

Entry requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related subject area. Master degree or lab experience is preferable, but not necessary.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website.

On the online application form select PhD Molecular Biology.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.