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Muscle Activity and Growth: from Developmental Genetics to the Human Population. The PDRAs will work collaboratively in the group of Professor Simon M. Hughes in the multidisciplinary Randall Centre to study:
Post 1) The role of physical force in the growth of skeletal muscle through a novel force-sensing system.
Post 2) The role of muscle stem cell heterogeneity in growth and repair of skeletal muscle.
The successful candidates will have deep understanding of experimental design and analysis in modern biomolecular and genetic research, and will work with zebrafish.
Post 3) The genetic and environmental causes of sarcopenia, ageing-related muscle wasting. This project, in collaboration with genetic epidemiologist and health data scientist Dr Nick Dand (KCL), will employ UK Biobank data to analyse the genetics and epidemiology of sarcopenia.
The PDRAs will join our MRC-funded team focused on understanding the molecular and cellular mechanisms of muscle growth, maintenance and repair. We want to know how exercise, nutrition and time of day interact with genetic predisposition to determine individual trajectory by generating hypotheses from human data and testing them in model systems. Experience with molecular genetics, timelapse confocal microscopy, zebrafish, equipment construction, physiology, GWAS, data analysis in R and muscle may all be advantageous.
This post will be offered on an a fixed-term contract until 31/10/2022.
This is a full-time post – 100% full time equivalent
Post 1) To develop new assays and protocols to assess the role of Forcin signalling, a novel pathway we have discovered that acts downstream of actomyosin activity to drive muscle growth. To use those approaches to determine the dynamics of regulatory changes and interaction with known pathways regulating muscle growth, such as TORC1.
Post 2) To ablate/perturb specific cell populations and examine the effect on myogenesis by timelapse confocal microscopy.
Post 3). To perform epidemiological analyses using the UK Biobank and generate hypotheses, or test those generated from our zebrafish studies, in the human population through PheWAs and GWAS analysis.
To analyse and interpret the data collected in the above studies, and to contribute to the preparation of publications describing the results
To work collaboratively within the experimental team to generate and test hypotheses on muscle growth and maintenance in zebrafish, other model species and/or humans.
The above list of responsibilities may not be exhaustive, and the post holder will be required to undertake such tasks and responsibilities as may reasonably be expected within the scope and grading of the post.
Skills, knowledge, and experience
Post 1) Is funded by the MRC to investigate the growth and maintenance of skeletal muscle. We recently discovered a new pathway by which mechanical activity promotes skeletal muscle growth. We have a candidate molecular regulator in this pathway, called Forcin, which interacts with, but it distinct from, other known systems regulating muscle growth, such as TORC1 signalling. The project will examine how Forcin activity is regulated by the physical force generated by actomyosin contraction during muscle activity. We expect the results to be transformative for understanding the regulation of muscle growth and the development of approaches to prevent or reverse muscle wasting conditions. The post-holder will be responsible for developing new molecular genetic approaches to understand Forcin regulation, including in vivo reporters in zebrafish.
Post 2) Is funded by the MRC to investigate the growth and maintenance of skeletal muscle. We recently discovered distinct behaviours in molecularly-distinct muscle stem cell subpopulations. The project will use developmental genetics to ablate or otherwise perturb function of each population and determine the effect on muscle. We expect the results to transform understanding of mechanisms of muscle growth and aid prevention or reversal of muscle wasting conditions. The post-holder will help develop new molecular genetic approaches to understand control of muscle fibre number and size.
Post 3) Is funded by the MRC to build on a recently-initiated collaborative study to use the cross-talk between fundamental studies of muscle cell biology and molecular genetics in the zebrafish and other model organisms to gain insight into sarcopenia, the ageing-related muscle wasting that affects some people worse than others. We want to discover the genetic and life-long lifestyle factors that cause sarcopenia, and what might be done at each life stage to mitigate it.
Online interviews are planned for the week of 18th October 2021. Selected candidates will then be invited for in-person lab visits to meet the team and to present their work. Immediate availability may be an advantage.
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