MSc by Research: DNA Replication Coupled Mechanisms that control cell fate transitions

About the Project

DNA replication is required for successful cell fate transitions across diverse physiological, experimental, and pathological contexts, involving factors often deregulated in human cancer and intellectual disabilities. The underlying mechanisms are fundamental for our understanding of organ homeostasis but are poorly understood. We have discovered a profound and rapid rewiring of the proteins that are recruited around DNA replication forks, upon differentiation of human induced pluripotent stem cells (iPSCs) into mesoderm. A large proportion of these proteins are epigenetic regulators that are potential driver of differentiation. The aim of this project is to explore the specific role of these epigenetic regulators in cell fate decisions.

To do so, we will develop a new technology to achieve targeted protein degradation specifically at replication forks.Using this approach, we will monitor changes in chromatin accessibility (ATAC-seq), and histone modifications (iPOND-MS). In parallel, using an established protocol in the lab, changes in nuclear organization and cell cycle remodeling will be assessed by quantitative high-throughput single cell imaging. In conclusion, this project encompasses a blend of discovery approaches using mass spectrometry and mechanistic studies to reveal how DNA replication contributes to the mechanistic diversity of cell fate transitions.

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.