Understanding genetic disease of the heart using human stem cells and gene editing

Starting September 2017, there is an exciting opportunity for an ambitious and driven PhD student to work in world class laboratories between the Universities of Nottingham and Birmingham on a project that will combine human induced pluripotent stem cells (hiPSC), Cas9/CRISPR gene editing technology, and advanced technologies in imaging, electrophysiology, calcium and force generation to understand atrial fibrillation of the heart.

In a project entitled, “Modulation of atrial function by common gene variants on chromosome 4q25: A study in human induced pluripotent stem cell (hiPSC) derived cardiomyocytes”, this studentship will generate cutting-edge information deciphering the genomic predisposition to AF combining the expertise in human stem cell technology and atrial fibrillation research of two world-leading research groups.

Approximately 30% of AF patients, especially those with early onset of the disease, carry a genomic predisposition to the arrhythmia. This studentship will use human induced pluripotent stem cells (hiPSC) to assess the atrial dysfunction predisposing to AF based on this genomic predisposition. The student will learn and apply Cas9/CRISPR technology in the group of Professor Denning to gene edit healthy hiPSCs, such that the only change to the genome is addition of a damaging set of genetic variants with high and low risk of developing AF. Using validated protocols, the cells will be matured into atrial cardiomyocytes and fibroblasts. The student will learn and apply high-end phenotyping of these cells in the labs of Professor Kirchhof and Chris Denning e.g. cellular electrophysiology, patch clamp and/or optical mapping of calcium and voltage release, as well as by calcium transients and contractility, with metabolic changes examined by mitochondrial analysis.

The successful student will be aligned with other research staff in the labs, who are working as part of international collaborations, which will provide support and training. For details see Kirchhof group www.birmingham.ac.uk/research/activity/cardiovascular-sciences/research/heart-failure-arrhythmias/index.aspx and Denning group www.nottingham.ac.uk/research/groups/stemcellbiology/.
It is essential that interested applicants contact Prof. Chris Denning in Nottingham ([Email Address Removed]; +44 [0]115 82 31236) or Prof. Paulus Kirchhof in Birmingham ([Email Address Removed]; +44 [0]121 4147042) before applying. The link for applications is www.birmingham.ac.uk/schools/mds-graduate-school/scholarships/mrc-impact/index.aspx and the deadline is Sunday 21st May 2017.