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Cytoneme-mediated morphogen transport during wound healing and regeneration

University of Exeter - College of Life and Environmental Sciences

Qualification Type: PhD
Location: Exeter
Funding for: UK Students, EU Students
Funding amount: The studentship will provide funding of fees and a stipend which is currently £15,609 per annum for 2022-23, on a full-time basis
Hours: Full Time
Placed On: 22nd October 2021
Closes: 6th December 2021
Reference: 4270

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. 

* 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). 

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