Dr S MacNeill
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Post-translational modifications (PTMs) play key roles in the regulation of chromosomal DNA replication and DNA repair in eukaryotic cells and have been shown to have a significant impact on genome stability. We have established a programme of work aimed at dissecting the role of PTM’s in modulating the function of two key DNA polymerase enzymes, DNA polymerase δ and DNA polymerase ζ, using the genetically tractable fission yeast S. pombe as a model system. DNA polymerase δ functions in lagging strand DNA replication (Okazaki fragment synthesis) and several DNA repair pathways, and comprises four subunits: PolD1 (p125), PolD2 (p50), PolD3 (p68) and PolD4 (p12). Two of these proteins (PolD2 and PolD3) also form part of the trans-lesion synthesis (TLS) enzyme DNA polymerase ζ.
We have identified several PTMs affecting these proteins and are in the process of characterising the biological role of the modifications. Initially, the student will take undertake the characterisation of S. pombe DNA polymerase δ and DNA polymerase ζ functions when PTM is prevented or reduced, thereby gaining key insights into the role of PTM in modulating protein function in the replisome and during DNA repair. A range of techniques spanning yeast genetics, molecular biology, biochemistry and proteomics will be used in order to ensure rapid progress. In the longer term, the student will investigate whether the regulatory mechanisms discovered in S. pombe are conserved in human cells by using CRISPR-Cas9 gene editing techniques to mutate PTM sites in the human polymerase subunits and a variety of assays to test the consequences of these mutations for human DNA replication and DNA repair.
The student will join a well-equipped lab with diverse interests in cell cycle control and chromosomal DNA replication and repair in yeast, archaea and trypanosomes (see http://biology.st-andrews.ac.uk/macneill for details), located in the Biomedical Sciences Research Complex (www.st-andrews.ac.uk/bsrc). The successful applicant should have a specific interest in the application of model systems to tackle questions of protein structure and function in eukaryotic cells. He/she will receive extensive training in the molecular genetic, molecular biological and biochemical techniques required to bring the project to a successful conclusion and will have opportunity to attend national and international meetings to present his/her data and to collaborate with groups elsewhere in St Andrews, the UK and abroad. Training will be further enhanced by participation in GRADskills, an extensive and award-winning generic skills development programme for early stage researchers. Informal enquiries can be directed to Dr Stuart MacNeill ([Email Address Removed]).
Funding Notes
This PhD will provide 3.5 years funding for UK or EU students. Students from outside those areas will be considered, but should be aware of the need to obtain additional funding to cover the difference between ‘home’ and ‘overseas’ fees. Enquiries from Chinese nationals are also particularly welcomed as the University of St Andrews has additional funding opportunities for Chinese students.
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