(MCRC Clinical) Tissue mechanics as regulator of therapy resistance in pancreatic ductal adenocarcinoma (PDAC)
Not stated
- Location
- Manchester, United Kingdom
- Funding
- Competition Funded PhD Project (Students Worldwide)
- Application deadline
- 23 November 2026
About the project
About the Project Pancreatic Ductal Adenocarcinoma is a treatment recalcitrant tumour, driven by activation of the proto-oncogene KRAS. Recent development and clinical testing of KRAS inhibitors has demonstrated clinical benefits in second-line pre-treated patients, however development of resistance and disease progression is inevitable. While mechanisms of resistance remain poorly defined, genomics data have failed to identify genetic mechanisms in up to 60% of patients and mechanistic studies have revealed a role of the mechano-regulator YAP. How the tissue microenvironment, tissue stiffness and response to KRAS inhibitors is mechanistically linked remains poorly understood. The objective of this proposal is to mechanistically interrogate the pathways by which tissue rigidity engages KRAS signalling and to develop approaches to alleviate such bypass mechanisms. This is a fundamental mechanistic lab-based project using a combination of tissue analysis, in vitro human patient derived models, synthetic hydrogel scaffolds, cell signalling analysis and CRISPR perturbation. Eligibility You must be a post-registration clinician and therefore must hold an MBChB degree or equivalent medical degree and ideally have a specialist post in a related subject, to apply for our Clinical Research Training Fellowships. It is generally expected that CRTFs will return to a training programme in the UK upon completion of their research degree. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study. You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester Application Timeline Applications open: Monday, 5 October 2026 Application deadline: Monday, 23 November 2026 Interview date: Week commencing 11 January 2027 Start date: September 2027 Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/”