Investigation of the role of RNA:DNA hybrids in telomere stability and differentiation of hematopoietic stem cells

Supervisors: 

Dr Panagiotis Kotsantis, Faculty of Health and Medicine (Lancaster University)

Dr Karen Keeshan, School of Cancer Sciences (University of Glasgow)

Dr Nikki Copeland, Faculty of Health and Medicine (Lancaster University)

Summary: 

Hematopoietic stem cells (HSCs) ensure production of all blood cells throughout adult life. As they age, HSCs gradually lose their self-renewal and regenerative potential. 

Telomeres are nucleoprotein structures that protect chromosome ends. With each cell division, telomeres shorten because of the inability of DNA polymerase to fully replicate telomeres. When telomeres reach a critical length, this triggers senescence and the cell dies. 

RNA:DNA hybrids (also known as R-loops) normally form during DNA transcription but participate in several physiological cellular processes. In particular, they have been reported to facilitate telomere stability and telomere length determines RNA:DNA hybrids accumulation at telomeres. Increased R-loop levels have been reported to compromise embryonic stem cell differentiation. 

This project aims to determine how telomeric RNA:DNA hybrids regulate HSCs differentiation, and it will develop basic research knowledge that holds the potential to prevent, delay, or even reverse aspects of the HSC decline process upon stress. 

An expert and experienced research team from Lancaster University and University of Glasgow is in place to supervise and support the PhD student, with opportunities for research and training in molecular, cell and stem cell biology. You will gain skills in stem cell handling, telomere biology, R-loop biology, DNA replication dynamics and immunofluorescence-based techniques.