This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).
Project Description:
The determination of the cellular fate is one of the most fundamental and classical problems in regeneration. In many tissues, cell fate is determined by morphogen signalling proteins.
Two families of morphogens, namely Shh and Wnt - are essential for determining many fundamental aspects such as cell proliferation, differentiation and migration. We and others have shown that the distribution of these morphogens can be facilitated by membrane protrusions - also known as cytonemes. Cytonemes are thin, actin-rich, and transport essential components of the Shh and Wnt signalling pathway between cells (Zhang and Scholpp, 2019; Curr Opin Gen & Dev). Cytonemes are highly dynamic and can form and retract within minutes (Stanganello et al., 2015; Nat Comms).
Their emergence is precisely controlled by the cytoneme-producing cell and the extracellular space through which they traverse (Brunt, et al., 2021, Nat Comms). Although there is strong evidence that Wnt3a and Shh cooperate during wound healing, to date, it is unknown how their crosstalk is regulated. Furthermore, the role of cytoneme-mediated transport during wound healing is unclear.
Under the supervision of leading cell and developmental biologists, the student will study Wnt and Shh transport in the regenerating fin in zebrafish. The student will generate transgenic zebrafish lines in which signalling components are fluorescently tagged to investigate cytoneme-based morphogen release by quantitative imaging. We will also use real-time PCR, single-molecule fluorescence in-situ hybridisation, and advanced high-resolution microscopy in the wound to describe signal activation. Finally, the student will interfere with the emergence of cytonemes by using chemical inhibitors and CRISPR/Cas9-based mutations to study their impact on zebrafish wound healing.
The student selected for this project will develop invaluable skill sets in experimental genetics, developmental biology, and high-resolution microscopy, whilst also making a significant contribution to the understanding of a cell fate specification. This combined skill set will make the candidate a highly desirable recruitment prospect for future academic and industrial employers.
The Living Systems Institute (LSI), with complementary expertise in biosciences and high-resolution imaging, will be an optimal environment to conduct these doctoral training studies.
The LSI offers unique training opportunities for the PhD student. It allows the student to address key problems in life sciences with state-of-the-art equipment in an interdisciplinary environment. The project includes an extended placement in the lab of Prof Paul Martin (University of Bristol) - an international leading expert in wound healing and signalling biology.
Eligibility
To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria.
A fully-funded four year SWBio DTP studentship will cover
• a stipend* at the standard Research Council UK rate; currently £15,609 per annum for 2022-23
• research and training costs
• tuition fees (at the standard Research Councils UK rate)
• additional funds to support fieldwork, conferences and a 3-month internship
Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship. Any further queries in relation to residency must be directed to the institution that you are applying to.
* An enhanced stipend is available for students with a recognised veterinary degree qualification (£24,090 per annum for 2022-2023). There may also be enhanced stipends associated with projects that have a CASE partner (CASE projects are highlighted as *CASE in the project lists).
Entry Requirements
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Masters degree or have significant relevant non-academic experience.
In addition, due to the strong mathematical component of the taught course in the first year and the quantitative emphasis in our projects, a minimum of a grade B in A-level Maths or an equivalent qualification or experience is required.
Equivalent qualifications/experience
Physics A-level (grade B and above)
Undertaking units as part of your degree that have a significant mathematical component*
*Significant mathematical component examples include; maths, statistics, bioinformatics.
Applicants must ensure they highlight their Maths background within their application and to upload any supporting evidence.
Language Requirements
If English is not your first language you will need to have achieved at least 6.5 in IELTS and no less than 6.5 in any section by the start of the project. Alternative tests may be acceptable, please see http://www.bristol.ac.uk/study/language-requirements/profile-c/.
How to apply
In order to formally apply for the PhD Project you will need to go to the following web page.
https://www.exeter.ac.uk/study/funding/award/?id=4270
The closing date for applications is midnight on Monday 6th December 2021.
Interviews will be held between Monday 24th January – Friday 4th February 2022.
If you have any general enquiries about the application process please email [Email Address Removed] or phone: 0300 555 60 60 (UK callers) or +44 (0) 1392 723044 (EU/International callers). Project-specific queries should be directed to the main supervisor.
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