(MCRC Non-Clinical) Investigating the role of heterogeneity and plasticity in small cell lung cancer invasion

About the project

About the Project Small cell lung cancer (SCLC) is among the most aggressive cancers. Approximately 80% of patients present with metastatic disease at which stage treatment options are limited, and median survival <1 year. A key reason for the aggressiveness of this disease is tumour plasticity (wherein cells change their phenotypes) leading to tumour heterogeneity (the tumour comprises diverse phenotypes). Most tumours contain mostly neuroendocrine (NE) cells mixed with a minority of a nonneuroendocrine (non-NE) population. Transition from NE to non-NE states generates this mix, and cooperation between the two populations is required for invasion and metastasis as well as drug resistance.There is limited understanding of what triggers this transition because standard cell lines mostly utilised to study SCLC possess little plasticity. Our team leverages unique patient-derived circulating tumour cell explant (CDX) models that retain spontaneous NE to non-NE transition, providing a powerful platform to uncover mechanisms that drive SCLC progression. This studentship will explore how microenvironment signalling initiates and propagates the NE to non-NE transition, enabling invasion and metastasis of SCLC cells. To this end, the student will implement cellular assays to follow fate switching, 3D culture assays to study the impact of microenvironmental factors and plasticity on invasion, and kinome profiling to implicate critical kinases that are actionable. Training will span molecular and cell biology, flow cytometry, and microscopy as well as data-driven screening within a collaborative and inclusive supervisory environment, all within state-of-the-art laboratory and office space. The training offered by the studentship will also deliver broad transferable skills for a successful PhD and a career in cancer research. Eligibility You must hold, or about to obtain, a minimum Upper Second Class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. A related master’s degree would be an advantage 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/

Research areas