PhD Research Project: Integrity of mitochondrial DNA in human pluripotent stem cells and implicatio

Human Pluripotent Stem Cells (hPSCs) have the ability to produce cells of all tissues within the body. They can provide a valuable tool for modelling human disease, as well as a potential source of differentiated cells for use in regenerative medicine and drug discovery. In order to fulfil the therapeutic potential of hPSCs it is important to ensure their genome is free of any potentially deleterious mutations that could either impair the function of the hPSC-derived differentiated derivatives or give rise to malignant phenotypes upon transplantation in vivo. Recurrent genetic changes have been noted in the nuclear genome of hPSCs that appear to confer selective growth advantage to the variant cells. Less understood is the appearance and role of mutations in the mitochondrial genome of hPSCs. This project will focus on investigating the extent of mitochondrial DNA instability, molecular mechanisms that underpin mutation generation and the functional consequences of the mutations on hPSC phenotype and behaviour. Techniques will include a range of molecular and cellular biology methods, including hPSC culture, genetic manipulation of hPSC using CRISPR/Cas9, flow cytometry and live cell imaging.

Funding Notes

Applications from self-funded students or students with secured funding are also welcome.
Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.