BBSRC White Rose DTP CASE Studentship with AstraZeneca - The causes and consequences of mitotic errors in embryonic stem cells

Human embryonic stem cells (ESC) represent powerful tools for modelling early embryogenesis and provide a source of differentiated cells for use in regenerative medicine applications. The assurance of genetic stability is essential for uses of ESCs in basic research and regenerative medicine. Nonetheless, ESCs are known to acquire genetic changes upon prolonged culture. With ESC derivatives entering the clinical trials, a possibility that genetic changes may confer malignant properties to ESCs or their differentiated progeny is a major cause of regulatory concern. In our work we are elucidating the molecular mechanisms that underlie the maintenance of the integrity of the ESC genome, and how disruption of these mechanisms can lead to undesired genetic changes. We are also studying the functional effects of genetic changes on the behavior of ESCs and their differentiated derivatives.

We have recently demonstrated that ESCs exhibit a high frequency of mitotic errors (Zhang et al., 2019 Stem Cell Reports 12:557; Halliwell et al., 2020 Stem Cell Reports 14:1009) and parallel studies in early embryos indicated that such errors are an intrinsic property of early embryonic cells. Here, you will investigate molecular mechanisms governing a high incidence of mitotic errors in ESCs and you will assess the impact of chromosome gains or losses (collectively known as aneuploidy) on the developmental potential of ESCs. You will be embedded in a vibrant research environment at the Centre for Stem Cell Biology, the University of Sheffield, and a part of your project will be spent on a placement at AstraZeneca (Cambridge).

This project uses human pluripotent stem cell technology, coupled with molecular and cell biology approaches, including the use of CRISPR/Cas9.

Main supervisor: Dr Ivana Barbaric, the University of Sheffield
Second supervisor: Dr Mick Fellows, AstraZeneca

For informal enquiries please contact Dr Ivana Barbaric [Email Address Removed]