Identification of novel regulators of skeletal muscle mass

About a third of elderly admissions to long-term health care facilities are due to frailty and inability to perform daily living activities. With the growing demographics of the elderly in Western societies, understanding the mechanisms of muscle development and maintenance becomes increasingly important. Muscle mass can differ by more than two fold between same sex, height and age healthy adults. Genetic factors account for a substantial fraction of that difference, with heritability estimates 30-40% in both humans [1] and animal models [2]. In a genome-wide association analysis of a large population of healthy middle age individuals (UK Biobank project 26746) we have identified hundreds of genes and regulatory regions associated with variability in muscle mass [3]. We also found that the same genetic architecture is associated with muscle mass differences in the elderly. A large number of the genes are novel, not previously implicated in myogenesis. Our group aims to follow-up these findings in vitro. Novel genes and regulatory regions might offer targets for pharmacological interventions that in the future could prevent or reverse muscle loss due to aging or disease.

The project will focus on prioritising the coding and regulatory DNA targets for the experimental screening, examining effects of novel genes on myogenesis, and determining regulatory DNA sequences associated with muscle mass differences in humans.

This project will provide training in bioinformatics techniques, as well as wet lab training in cell and molecular genetics techniques, immunocytochemistry and imaging. In addition to the training in the academic institution, the student will also have a 3-month placement with Synpromics, the leading developer of synthetic promoters and provider of gene expression solutions to the Biotech industry.