Pluripotent stem cells (PSCs) in the early embryo give rise to all of the somatic cells in the body. Maintenance of the genetic integrity of PSCs is essential for preventing genetic defects to be passed onto multiple progeny cells, which would be detrimental for a developing embryo. When placed under appropriate culture conditions, PSCs retain the ability to give rise to differentiated cells from all three embryonic germ layers, whilst acquiring the ability to self-renew extensively and thus provide an excellent, genetically normal model system to investigate mechanisms that control genome integrity. We and others have previously shown that PSCs acquire non-random genetic changes upon prolonged culture. However, the molecular mechanisms underlying their acquisition remain poorly understood. To this end, our project will determine the contribution of different genome damage mechanisms to the common genetic changes we observe. We will also elucidate how extrinsic environment (specifically, culture medium composition) enhance or diminish these damage mechanisms.
Techniques will include PSC culture, CRISPR/Cas9 genome editing, high-resolution and time-lapse imaging and general molecular biology and biochemistry techniques. The student will also get an opportunity to work in an industrial setting, with our industrial collaborator Albumedix.
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