Immunosenescence in cardiovascular disease

Having heart surgery can come with some risks, such as organ injury. If patients have two or more long-term health issues (e.g. diabetes, cancer, etc.), their risk is increased. Therefore, it is an international research priority to identify the underlying pathways that make people with two or more long term health conditions susceptible to external stressors (e.g. infection, trauma, or surgery).

In our previous work, we’ve identified innate immune system activation and homeostatic inflammation in people with less severe chronic diseases, and T cell exhaustion, dysregulated tissue resident macrophage activity, and dedifferentiated cardiomyocytes in people with more severe disease. People in the latter group experience more severe organ injury, and slower recovery post-surgery.

We therefore aim to further explore this by identifying underlying processes and biomarkers that will allow development of accurate diagnostic tests to reverse or prevent risk with targeted treatments.

The aim of this project will be to use high precision -omics such a single cell RNA sequencing to simultaneously characterise bone marrow progenitor cells and heart cells collected from patients undergoing surgery. Data obtained from these experiments will be analysed through bioinformatics analysis methods to identify molecular signatures that can be measured by diagnostic tests, and/or druggable targets for new treatments. The identified targets/ processes will be validated using RNAScope in situ hybridisation, qRT-PCR, western blotting and ELISA amongst other molecular biology techniques.

The aim of the studentship is to develop familiarity with the most modern research techniques, and skill sets of value to world class research groups as future early career researchers.

Enquiries to project supervisor: Professor Gavin Murphy gjm19@le.ac.uk

Full details and application form see https://le.ac.uk/study/research-degrees/funded-opportunities/cvs-murphy