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  Mending the pipes: Defining defects in angiogenesis using zebrafish and human tissue culture to rescue healing in diabetic wounds


   Department of Life Sciences

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  Dr David Gurevich  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

The University of Bath is inviting applications for the following funded PhD project.

Funding is available to candidates who qualify for Home fee status. Following the UK’s departure from the European Union, the rules governing fee status have changed and, therefore, candidates from the EU/EEA are advised to check their eligibility before applying. Please see the Funding Eligibility section below for more information.

During tissue repair, effective angiogenesis is vital to supply repairing tissue with the nutrients and oxygen required by highly metabolically-active proliferating cells. Diabetes causes endothelial dysfunction and a failure of wound angiogenesis, one of the key drivers of compromised wound healing. These compromised wounds afflict millions of people globally: 15-25% of sufferers of diabetes develop poorly-vascularised, non-healing wounds such as foot ulcers, with the most severe of these requiring amputation. Crucially, compromised wounds often prove unresponsive to current clinical approaches, resulting in an urgent demand for an improved understanding of these defects at the genetic, cellular and tissue level to inform future therapeutics.

This project aims to identify angiogenic mechanisms that are dysregulated in diabetic wounds, modeling wound healing using zebrafish, which have essentially all components of mammalian tissue but with the added advantage of being translucent and genetically tractable. Zebrafish are therefore ideal for non-invasively live imaging tissue repair processes, as well as for rapidly screening candidate genes for their role in regulating wound angiogenesis using recent advances in CRISPR gene-editing. Building on our recent work, we will complement these fish wound healing investigations with human tissue culture assays, using this cross-species approach to validate the identified mechanisms in a translationally-relevant model. Ultimately, the results of this interdisciplinary project will drive understanding in how to restore wound angiogenesis to subsequently rescue tissue repair, providing models to identify novel therapeutic interventions.

This project will address the following key questions:

  1. What are the key genes and pathways that are dysregulated in diabetic wounds? We will combine RNAseq and proteomics analysis of wounded tissue from healthy and diabetic zebrafish to identify these targets.
  2. How do these candidate genes/pathways mechanistically result in defective angiogenesis in diabetic wounds? We will use cutting-edge genetic manipulations of zebrafish (CRISPR and tissue specific CRISPR-interference), combined with state-of-the-art live imaging approaches. 
  3. Are these mechanisms conserved in human tissues? We will validate the candidates identified in our fish studies via co-culture assays that generate vessels in vitro, using endothelial cells from healthy volunteers and diabetic patients together with siRNA knock-down approaches to dissect specific genetic mechanisms.

Candidate Requirements:

Applicants should hold, or expect to receive, a First Class or good Upper Second Class Honours degree (or the equivalent). A master’s level qualification would also be advantageous.

Non-UK applicants must meet our English language entry requirement.

Enquiries and Applications:

Informal enquiries are welcomed. Please contact Dr David Gurevich ([Email Address Removed]).

Formal applications should be made via the University of Bath’s online application form for a PhD in Biochemistry.

More information about applying for a PhD at Bath may be found on our website.

Funding Eligibility:

In order to be considered for a studentship, you must qualify as a Home student. In determining Home student status, we follow the UK government’s fee regulations and guidance which, when available, will be set out by the UK Council for International Student Affairs (UKCISA) on their website. Although not yet confirmed, we expect that the main categories of students generally eligible for Home fee status will be:

  • UK nationals (who have lived in the UK, EU, EEA or Switzerland continuously since September 2018)
  • Irish nationals (who have lived in the UK or Ireland continuously since September 2018)
  • EU/EEA applicants with settled status in the UK under the EU Settlement Scheme (who have lived in the UK continuously since September 2018)
  • EU/EEA applicants with pre-settled status in the UK under the EU Settlement Scheme (who have lived in the UK, EU, EEA, Switzerland or Gibraltar continuously since September 2018)
  • Applicants with indefinite leave to enter/remain in the UK (who have been resident in the UK continuously since September 2018)

EU/EEA citizens who live outside the UK are unlikely to be eligible for Home fees and funding.

Additional information may be found on our fee status guidance webpage and on the GOV.UK website.



Funding Notes

A studentship includes Home tuition fees, a stipend (£15,609 per annum, 2021/22 rate) and research/training expenses (£1,000 per annum) for up to 3 years. Eligibility criteria apply – see Funding Eligibility section above.

References

Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression. Gurevich DB, Severn CE, Twomey C, Greenhough A, Cash J, Toye AM, Mellor H, Martin P. EMBO Journal. 2018 Jun 4: 1-23.

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