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MRC DiMeN Doctoral Training Partnership: Ciliogenesis and skeletal muscle regeneration: molecular mechanisms of stem cell maintenance

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  • Full or part time
    Dr A G Borycki
    Prof Colin Johnson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Project:
Ciliopathies are a group of inherited developmental disorders caused by mutations affecting the structure or function of motile and non-motile cilia. Non-motile cilia (or primary cilia) are cellular organelles present on the surface of vertebrate cells that have essential functions in mechanotransduction, and regulating developmental signalling pathways and cell fate. Ciliopathies are multi-organ disorders that are characterized by developmental defects of the kidneys, eye and central nervous system. We recently reported that primary cilia are present in skeletal muscles and may have important functions in the control of skeletal muscle stem cell activity, muscle growth and regeneration. This raises the intriguing possibility that muscular defects are associated with some ciliopathies.
This project will investigate the role of primary cilia in skeletal muscles, in particular in the control of skeletal muscle stem cell activity. The project will use a combination of multidisciplinary techniques in molecular biology and muscle cell biology. The project will provide extensive training in ex vivo systems used to investigate myoblast fusion and differentiation, in vivo approaches using genetic mouse models and imaging techniques that will include confocal microscopy and wide-field live cell imaging. Transcriptome studies and bioinformatics will identify target genes of primary cilia function in skeletal muscle stem cells, in order to understand the mechanisms that control stem and progenitor cell production. The research may lead to insights and new approaches to alleviate muscle wasting in a range of skeletal muscle diseases and in the ageing population, and may inform novel drug developments that could regulate stem cell activity.

The project provides an exciting opportunity to start a research career in the new field of stem cell biology. You must demonstrate a strong background in molecular cell biology with a first degree in a relevant biomedical subject, and have the ability and ambition to develop a successful multidisciplinary research project.

Supervisors web pages:
https://www.sheffield.ac.uk/bms/research/borycki - tab01
https://medicinehealth.leeds.ac.uk/medicine/staff/478/professor-colin-a-johnson

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: https://goo.gl/8YfJf8
Good luck!

References

Jaafar Marican NH, Cruz-Migoni SB, Borycki AG. Asymmetric Distribution of Primary Cilia Allocates Satellite Cells for Self-Renewal. Stem Cell Reports. 2016 Jun 14;6(6):798-805. doi: 10.1016/j.stemcr.2016.04.004.

Malicki JJ, Johnson CA. The Cilium: Cellular Antenna and Central Processing Unit. Trends Cell Biol. 2017 Feb;27(2):126-140. doi: 10.1016/j.tcb.2016.08.002.

Logan CV, et al. (2011). Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nat. Genet. 43: 1189–1192.


REF2014:
The department of Biomedical Science (University of Sheffield) was ranked 1st for Medical Research Excellence and 5th for Biological Sciences in the REF2014.
The University of Leeds is rated a Top 100 university in the world (QS World Rankings 2019) and research is 85% "world-leading" or "internationally excellent" (REF 2014)



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