Gene editing for therapeutic sulfide elevation to reverse accelerated ageing in vivo

MRC DTP in Precision Medicine

Up to 26 fully funded studentship positions are available across the University of Glasgow and Edinburgh. Our next intake will be for PhD projects commencing September 2017.

The Precision Medicine Doctoral Training Programme (DTP) offers PhD with Integrated Study studentships funded by the Medical Research Council (MRC), The University of Edinburgh and the University of Glasgow. Hosted by the University of Edinburgh in collaboration with the University of Glasgow and the Karolinska Institute, this prestigious programme provides PhD research training alongside taught courses over four years of study and welcomed its first cohort of students in September 2016.

This new Doctoral Training Programme focuses on training PhD students in key MRC skills priorities in quantitative skills (mathematics, statistics, computation, and developing digital excellence) as applied to variety of data sources (from ‘omics’ to health records), and interdisciplinary skills including imaging and stratified medicine.

Supervisors
Prof Colin Selman - [Email Address Removed]
Prof Nik Morton - [Email Address Removed]
Dr Joanna Rorbach - [Email Address Removed]
Prof George Baillie - [Email Address Removed]

Abstract
The number of people over 60 will rise from 12% (900M) to 22% (2Bn) of the total global population by 2050. Advancing age greatly increases all-cause mortality but we still know very little about the common underlying mechanisms. Therapeutic intervention for ageing remains one of the last great barriers in science. One emerging mechanism for slowed ageing is increased hydrogen sulfide (H2S) production, and we have recently shown that altered levels of the mitochondrial H2S-metabolising enzyme thiosulfate sulfur transferase (TST) associates with metabolic health. TST modulation represents a unique target for determining the impact of H2S, in particular within the mitochondria; organelles that appear to be critical players in ageing and pathology. In this project you will test the hypothesis that mitochondrially-targeted, therapeutic elevation of H2S through Tst deletion will reverse aspects of the rapidly ageing phenotype of Zmpste24–/– mice, a model of human progeria. The PhD will utilize a number of highly integrative cutting-edge techniques (CRISPR gene-editing, metabolic analysis, mass-spectrometry, mitochondrial functional analysis) to determine the role of H2S on ageing and disease. This interdisciplinary project offers training at the Universities of Glasgow, Edinburgh and The Karolinska Institute (Sweden) with which to test a novel anti-ageing hypothesis practically within the time-frame of a PhD.