Using genome engineering and bioinformatics to understand heterochromatin and centromere function in Schizosaccharomyces pombe and in cancer cells


   School of Life Sciences

  Dr W R A Brown, Dr W Wickstead  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Centromeres are the DNA sequences on eukaryotic chromosomes that mediate accurate chromosome segregation at both mitotic and meiotic cell divisions. Despite mediating conserved and essential biological functions centromeres vary extensively in evolution. The molecular differences between the different types of centromere is not understood because of the fact that it is superimposed upon widespread interspecies variation. The fission yeast Schizosaccharomyces pombe is a single celled eukaryotic microorganism with a fully developed classical and molecular genetics and is perfect for the molecular analysis of cell autonomous function as the cells grow quickly, the genome is small, easy to manipulate (Barbosa et al., 2022) and underpinned by superb online resources https://www.pombase.org/. Schizosaccharomyces pombe is, uniquely, able to form at least three types of centromere. The project will use CRIPR interference, molecular and classical genetics as well as genomic tools such as ChIP~seq and whole genome sequencing to understand the differences between these different types of centromere. The fact that S. pombe is such an excellent experimental organisms makes it ideal for a PhD project as experiments can be carried out inexpensively and quickly.

The reason we are pursuing this project is that centromeres also vary in human cancer cells but the molecular basis of this variation has not been investigated. We intend to use the results obtained in S. pombe to help start this line of work and identify new therapeutic targets. The prospective student needs to be numerate, keen to expand their coding and modelling skills and enjoy lab work. The PI on this project works almost full time at the bench and the student will receive all the support necessary to make good progress. We collaborate with labs in the US (Virginia Tech) and Japan (Kurume). PhD students should aim to secure at least one first author paper in a good journal as a result of their studies

Biological Sciences (4)

References

Barbosa, A.C., Xu, Z., Karari, K., Williams, W., Hauf, S., and Brown, W.R.A. (2022). Mutation and selection explain why many eukaryotic centromeric DNA sequences are often A + T rich. Nucleic Acids Res 50, 579-596

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