Targeting small cell lung cancer plasticity and heterogeneity to tackle metastasis and drug resistance
Closing date: 17/11/2025
Non-Clinical Studentship Project: Targeting small cell lung cancer plasticity and heterogeneity to tackle metastasis and drug resistance
Lead Supervisors: Prof. Angeliki Malliri
Co-Supervisors: Dr Kathryn Simpson, Dr Colin Lindsay, Prof. Caroline Dive
Applications Deadline: 12:00pm Monday 17th November 2025
Interviews: Week commencing 12th January 2026
Start date: September 2026
Project Keywords: Small Cell Lung Cancer, Tumour heterogeneity, Growth Factor Signalling
Research Opportunity: Non-Clinical Studentship leading to the award of PhD
Project Outline
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. Our pilot data highlight a central role for growth-factor stimulation and the downstream signalling mediator RAC1 in driving NE to non-NE transition. This studentship will explore how growth-factor– RAC1 signalling initiates and propagates the NE to non-NE transition, enabling invasion, metastasis and drug resistance of SCLC cells. To this end, the student will implement cellular assays to follow fate switching, kinome profiling to implicate critical kinases that are actionable, and proximity labelling and allied proteomics to explore the RAC1 signalosome.
Training thus spans molecular and cell biology, flow cytometry and microscopy, proteomics, and data-driven screening within a collaborative and inclusive supervisory environment, all within stateof- 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.
Applications for this project are now open. Please complete your application on The University of Manchester website.
About Prof. Angeliki Malliri (project Lead Supervisor)
Angeliki completed her bachelor’s degree in Biology at the University of Patras, Greece and obtained her PhD from the University of Crete, Greece. She worked as a postdoctoral scientist at the CRUK Beatson Institute in Glasgow and the Netherlands Cancer Institute in Amsterdam.
She established her independent research group in 2004 at CRUK Manchester Institute and moved to the Division of Cancer Sciences of the University of Manchester in March 2024. A focus of her laboratory has been the mechanisms controlling and mediating cell migration and invasion, definitive characteristics of malignant cells essential for metastasis. For this, they have been concentrating on Rho-like GTPases and in particular the Rho-like GTPase Rac1 because of its importance in cytoskeletal organization, cell polarity, adhesion and extracellular matrix remodelling required for migration and invasion.
Key information
Before submitting an application, please ensure you have read the information below about the funding arrangements and eligibility for Non-Clinical Studentships.
We also encourage you to get in contact with the lead supervisor to discuss the project and any particulars.
Further information is available on the Non-Clinical PhD Studentships webpage.
Our Non-Clinical PhD Studentships are usually funded for four years, with funding covering:
- Project running costs
- University tuition fees university tuition fees (at the UK rate, with some scholarships available for high-performing EU/International candidates)
- An annual stipend of £22,113to help with living costs
Studentships are highly competitive and so we encourage you to contact any supervisors who you are interested in working with before applying for our Non- Clinical PhD Studentships.
International Candidates
The University of Manchester aims to support the most outstanding applicants from outside the UK.
We are able to offer a limited number of bursaries to high-performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges.
We assess each EU and international candidate’s suitability for a bursary at the application and interview stages.
You must hold, or be about to achieve, a First or Upper Second-class honours degree in a relevant subject. A related Master’s degree is also 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.
Applications for this programme are now open. Please submit your application on The University of Manchester application portal.
Key dates
- Applications open: Monday 6th October 2025
- Application deadline: 12:00pm Monday 17th November 2025
- Interviews: Week commencing 12th January 2026
- Start date: September 2026
Useful Links
Submit your application
Interested in applying for this opportunity? Submit your application on The University of Manchester application portal.
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