Dr H Ferreira
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Telomeres are protein-DNA structures that protect the ends of linear chromosomes. Telomeres shorten every time cells replicate and are therefore strongly linked to cellular aging. Curiously, although telomeres prevent chromosome ends being recognised as DNA double-strand breaks (DSBs), telomere maintenance requires the presence of DNA repair proteins. How the DNA damage response is regulated to differentiate short telomeres from DSBs is one of the great mysteries of telomere biology. Given that SUMO modification is heavily implicated in both DNA repair and telomere length maintenance (1), one hypothesis is that sumoylation may help to define the appropriate DNA damage response.
This project aims to test this hypothesis using budding yeast, Saccharomyces cerevisiae, as a genetically tractable model organism. We will engineer yeast strains to controllably induce efficient telomere elongation. Additionally, by introducing a tagged SUMO variant into these cells we will identify not only the identity of which proteins get SUMO modified during telomere elongation but also the specific residue that is modified (2). There are published mass spectrometry data on the global SUMO response after UV and MMS-induced DNA damage in budding yeast (3). We will be able to compare our results with these data to test the hypothesis that the sumoylation response in response to telomere elongation is sufficiently distinct to that of generic DNA repair that it may function to direct the correct DNA damage response at chromosome ends. The functional role of SUMO modification of specific target proteins will be followed up in subsequent assays monitoring telomere length and DNA damage sensitivity. This work will help to address how normal telomere length is regulated as part of healthy aging.
As this project covers both in vivo and in vitro analyses, the student will receive training in a wide variety of skills including: molecular biology and cloning, yeast genetics, protein purification and the generation and analysis of mass spectrometry data.
Funding Notes
Enquiries from Chinese nationals are particularly welcomed as the University of St Andrews has additional funding opportunities for Chinese students.
References
1. Ferreira H et al., Nature Cell Biology 2011
2. Tammsalu, T et al., Nature Protocols 2015
3. Psakhye and Jentsch, Cell 2012