Summary
Gastric cancer is a multifactorial disease-causing over a million deaths yearly. Deregulation of oncogenic cell signalling, such as the Wnt signalling pathway, leads to tumour growth and metastasis. In this project, the student will apply novel microfluidic tools to decipher the function of Wnt signal spreading and activation in the tumour microenvironment to develop effective new therapeutics to combat
gastric cancer.
Details
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. There is an urgent need to develop novel therapeutic approaches to improve prognosis. A complex interplay in the tumour microenvironment promotes gastric cancer development. Deregulation of oncogenic cell signalling pathways such as the Wnt signalling pathway leads to the acquisition of malignant phenotypes, including tumour growth and metastasis. Mutations in Wnt- related tumour suppressor genes are closely associated with transforming normal gastric epithelium into adenomas. Concomitantly, elevated expression of Wnt ligands and receptors is essential for tumour progression. However, Wnt ligands and receptors are only expressed by a few cell types within the tumour tissue. Thus, there is a pressing need to improve our understanding of Wnt dissemination within a tumour.
Recently, we have broken new ground by showing that signalling filopodia, known as cytonemes, transport Wnt proteins in tissues (Stanganello et al., 2015, Nat Comms; Mattes et al., 2018, eLife; Brunt et al. 2021, Nat Comms). Our preliminary data suggest that cancer- associated fibroblasts and tumour cells produce different Wnt ligands and receptors. However, both use the same complex cytoneme network to disseminate and receive these signals in the tumour microenvironment. This discovery is potentially game-changing because it demonstrates the importance of the tumour cytoneme network and targeting this network could allow us to control signalling, hence tumour behaviour. In this project, the student will apply novel microfluidic tools to elucidate the exact function of Wnt cytonemes in the tumour microenvironment, specifically in gastric adenomas. Focusing on cancer- associated fibroblasts and gastric cancer cells, the student will develop a high-throughput method to screen for effective new therapeutics and characterise unknown tumour signalling properties. Concomitantly, the student will test for the function of Wnt signalling in the promotion of gastric cancer stemness, thus developing and optimising individual treatment regimes. In summary, we believe the outcomes of this project will fundamentally change our understanding of signalling in gastric cancer and provide novel and effective tools to study tumour microenvironment interactions in individual cancers.
How to apply
Applications open 2nd September and close at 17:00 on 2nd November 2022
To begin a GW4 BioMed MRC DTP studentship, applicants must secure an offer of funding from the DTP.
Stage 1: Applying to the DTP for and Offer of Funding
1. Select your projects from the project descriptions available on this website. You may select up to two projects in your application. If you are applying for the ICASE project you must choose this as your first choice project and is only open to UK citizens as indicated on the website.
2. Submit your application using this online form before 5 pm on Wednesday, 2nd November 2022.
3. Student shortlisting is conducted in a blind review of studentship applications by theme-specific panels. Up to 60 top candidates who emerge from this deliberation will be invited to interview.
4. Informal, virtual meetings will be arranged by the successfully shortlisted candidates with the lead supervisors of each project to which they have applied before the formal interview.
5. Formal interviews will occur virtually by theme-specific panels including representatives from each GW4 institution on 25-26 of January 2023.
6. Student selection for up to 20 funded studentships occurs after the formal interviews. Projects are allocated based on the rank of the successful candidates, therefore, it is not always possible to offer an applicant their first-choice project.
7. A clearing period will follow until approximately mid-March until all places have been offered and accepted. For this reason, it is not possible to provide immediate interview results to shortlisted applicants.
Stage 2: Applying to the lead institution for an Offer of Study
Once you have been offered a studentship with the GW4 BioMed MRC DTP, you will need to apply for an Offer of a Place at the home institution of your lead supervisor. Please note that each institution has different application processes.
Applicants for projects based at the University of Exeter should apply to the DTP first to secure an offer of funding. Once an offer of funding is issued by the DTP, you will receive more information on submitting a formal application to the relevant institution, guided by the DTP and local admin contacts.
Selection Criteria
Your online application forms will be evaluated against the following criteria:
Proven academic quality: normally evidenced by an excellent performance to first degree and/or Master’s level but may also be demonstrated by a record of relevant professional practice.
Research potential: evidenced through their supporting statement and supported by performance in research projects at first degree and/or Master’s level, or another form of dedicated preparation for research.
Personal motivation & commitment: evidenced through their supporting statement, by their enthusiasm for the project area and how they see it relating to their career goals.
Non-biomedical disciplines: In line with supporting interdisciplinary and quantitative skills, special consideration will be given by the interview panels to non-biomedical applicants. Such candidates should not feel the selection criteria are biased towards biomedical applicants as their unique skills will be taken into account.
Candidates selected to interview will be evaluated against the following criteria:
Critical thinking assessed via discussion of a student-selected piece of data
Fit with the project: The interview panel will evaluate the candidate’s aptitude and understanding of the key issues in the project, supported by feedback from informal meetings with the potential lead supervisor.
Personal commitment & motivation
For full information on the studentship including entry requirements/academic requirements/English language requirements and eligibility please visit - https://www.exeter.ac.uk/study/funding/award/?id=4513
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