Investigating the Role of Cancer Associated Fibroblast Senescence and sEVs in Triple-Negative Breast Cancer Stem Cell Dynamics

Entry requirements

To express your interest, please submit a CV, cover letter, and details of two academic referees. Include a brief statement (500 words) on why you are interested in this project and how your skills and experience align with the objectives.

For informal inquiries or further details, please contact Dr Berna Sayan (b.s.sayan@salford.ac.uk).

Join us in making a meaningful contribution to cancer research and improving outcomes for patients.

Months of entry

Anytime

Course content

Project Summary:

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high recurrence rates, therapy resistance, and poor prognosis. Radiotherapy is a cornerstone of TNBC treatment, but it can inadvertently alter the tumour microenvironment by inducing senescence in cancer-associated fibroblasts (CAFs). Senescent CAFs secrete a complex mixture of pro-inflammatory molecules, growth factors, and proteins in the form of small extracellular vesicles (sEVs), collectively termed the senescence-associated secretory phenotype (SASP). These sEVs can influence TNBC tumour heterogeneity by promoting cancer stem cell (CSC) expansion, invasion, and resistance to therapy.

This project will investigate how CAF senescence impacts sEV composition and their role in modulating TNBC CSC dynamics. This study aims to elucidate the mechanisms by which CAF-derived sEVs contribute to TNBC progression and therapy outcomes.

Key Objectives:

· Characterise sEV Cargo and Signalling: Isolate and analyse sEVs from CAFs to identify key proteins, microRNAs, and signalling molecules involved in modulating triple-negative breast cancer (TNBC) stem cell dynamics.

· Investigate sEV Effects on TNBC Cancer Stem Cells (CSCs): Assess the impact of CAF-derived sEVs on TNBC CSC proliferation, survival, epithelial-to-mesenchymal transition (EMT), and mammosphere formation using in vitro functional assays.

· Identify and Target Pro-Tumorigenic Pathways: Explore the signalling pathways (e.g., IL-6/STAT3, TGF-β/SMAD) activated by sEVs in TNBC CSCs and evaluate the potential of therapeutic strategies to inhibit these pathways and mitigate tumour-promoting effects.

Training and Skills Development:

The successful candidate will receive interdisciplinary training in cutting-edge techniques, including:

• Cell Culture: Culturing and maintaining cancer cell lines for experimental studies.
• Stem Cell Biology: Investigating BCSC populations using mammosphere assays.
• Extracellular Vesicle Research: Isolation, characterisation, and functional analysis of sEVs.
• Flow Cytometry and Fluorescence Microscopy: Investigating cell cycle, apoptosis, and treatment responses.
• Gene and Protein Expression Analysis: Measuring and modifying gene/protein activity to study pathway regulation.

These skills will equip the candidate with a robust toolkit for biomedical research, preparing them for careers in academia, industry, or clinical research.

Candidate Profile:

We are looking for self-funded PhD candidates with:

1. Curiosity and passion for scientific discovery.
2. Self-motivation and a proactive approach to problem-solving.
3. Enthusiasm for learning new techniques and concepts.
4. Resilience and a growth mindset, viewing challenges as opportunities for development.

Candidates should have a strong background in a relevant field (e.g., biomedical sciences, molecular biology). Prior experience in cell culture, stem cell biology or sEV, is advantageous but not essential, as comprehensive training will be provided.

Supervisory Team:

The candidate will benefit from an interdisciplinary supervisory team with expertise in biomedical research, medical genomics and sEV research, ensuring a supportive and enriching research environment.

Fees and funding

This programme is self-funded.

To enquire about University of Salford funding schemes – including the Widening Participation Scholarship – visit this website.