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DMD gene in development and cancer


Project Description

Applications are invited for a fully-funded three year PhD to commence in October 2020.

The PhD will be based in the Faculty of Science and Health, and will be supervised by Dr Matt Parker and Prof Darek Gorecki.

This project is part of an interdisciplinary programme of research led by Profs Darek Gorecki and Matt Guille and Drs Rhiannon McGeehan and Matt Parker.

DMD gene mutations result in Duchenne Muscular Dystrophy, which gave the gene its name. However, new data from our and other laboratories indicate that DMD mutations trigger downstream multi-system abnormalities going far beyond the mechanical instability in myofibres. These alterations are diverse and affect proliferation and signalling in specific cells, mitochondrial functions and metabolism and even oncogenesis. Moreover, cognitive deficits found in Duchenne patients are caused by distinctive molecular alterations resulting from DMD gene mutations in the brain cells. Given this increasing range of defects, identifying novel pathological mechanisms triggered by DMD mutations would advance our understanding of potential new roles of this largest human gene known in human health and disease.

The strategic aim of the three interdisciplinary PhDs is to expand DMD research into new areas by exploiting novel findings and high quality preliminary data. The projects are mutually supporting, creating the critical mass, using several animal models offering cross-species validation of findings and access to the university infrastructure across the faculties. They also involve 10 external partners offering laboratory placements and an extensive range of expertise. Therefore, while the majority of work will be undertaken in Portsmouth, each PhD student will spend a short period at a collaborating laboratory.

The work on this project will offer a broad-spectrum training including:
● Molecular and functional analyses in cancer cells
● Developmental and morphological studies in zebrafish
● Multi-omics data analyses

Using RNASeq and proteomics analyses we have evidence that, contrary to the current dogma, DMD mutations predominantly affect undifferentiated rather than terminally differentiated cells, in which we identified numerous abnormalities. This project will investigate the developmental effects of DMD mutations to establish whether an early treatment could prevent irreversible damage. This part of the project will also exploit dystrophic zebrafish, thereby using a less sentient developmental model offering a unique platform for behaviour and morphology analyses (using equipment in the Portsmouth Zeiss Global Centre). Importantly, the zebrafish model will be used for both this and the concomitantly run DMD brain study, creating the cross talk and cooperation opportunities for PhD students on these projects. Importantly, somatic DMD mutations have been associated with aggressive cancers. Given the commonalities in development and oncogensis, tumour formation might be a novel but related aspect of DMD gene dysfunction. The unique multi-omics data already available to us will be studied and the bioinformatics integration performed in collaboration with the Han Lab at the Milner Institute, Cambridge. The functional impact of DMD gene in oncogenesis will be studied in cancer cells, in collaboration with the Sicinski Cell Cycle Machinery in Development and Cancer lab at Harvard. Unravelling novel mechanisms triggered by DMD mutations in cancer might help developing new diagnostic and therapeutic tools for this condition. The PhD researcher will join a team using multidisciplinary approaches to analyse gene functions in health and disease. This project offers training in a range of techniques including multi-omics dataset analyses, cell culture in vitro, advanced microscopy and in vivo studies.

General admissions criteria
You’ll need an upper second class honours degree from an internationally recognised university or a Master’s degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency is required at a minimum of IELTS band 6.5 with no component score below 6.0.

Specific candidate requirements
You would have studied one of these: cell biology, biochemistry, developmental biology, pharmacology, neuroscience or a related molecular area and you would be keen to learn new things.

How to Apply
We’d encourage you to contact Prof Darek Gorecki () or Dr Matt Parker () to discuss your interest before you apply, quoting the project code.

When you are ready to apply, you can use our online application form. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process.

If you want to be considered for this funded PhD opportunity you must quote project code PHBM4781020 when applying.

Funding Notes

The scholarship covers tuition fees and an annual maintenance grant of £15,009 (UKRI 2019/20 rate) for three years. Scholarship recipients will also receive up to £3,000 for research project costs/consumables during the duration of the programme.

Related Subjects

How good is research at University of Portsmouth in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 23.80

Research output data provided by the Research Excellence Framework (REF)

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