Regulation of chromatin organisation by cytoskeleton regulators in non-small cell lung cancer

About the Project

Overview

This project will explore recently discovered mechano-sensitive cancer cell signalling pathways and seeks to understand the mechanisms by which force is transmitted from the tumour microenvironment into the nucleus to control tumour growth.

Background and hypothesis

Early diagnosis is one of the most powerful tools for improving cancer outcomes and reducing both the economic and personal burden of disease. Lung cancer remains the leading cause of cancer-related death worldwide, and its early detection is particularly challenging. To address this, we must better understand the biological mechanisms that drive tumour progression at its earliest stages.

This PhD project investigates how mechanical forces within the lung tumour microenvironment influence cancer cell behaviour and immune cell interactions. Gene dysregulation is a hallmark of cancer, and recent evidence suggests that physical changes in the extracellular matrix (ECM), such as tissue stiffening, can directly alter gene expression by transmitting force to the cell nucleus. However, the molecular mechanisms that link mechanical cues to gene regulation and immune modulation remain poorly understood.

We have discovered that a subset of cell adhesion proteins, typically found at the cell surface, can localise to the nucleus and regulate gene expression. Several of these proteins regulate the cytoskeleton, which transmits force from the cell surface to the nuclear envelope. This project will explore how selected cytoskeleton regulators contribute to mechanosensitive gene regulation and how this affects immune cell phenotypes in lung cancer.

Key approaches

You will use cutting-edge techniques, including genome editing, tuneable biomaterials, proximity-dependent proteomics and quantitative mass spectrometry, chromatin mapping, RNA sequencing, immune profiling and advanced microscopy.

Team

This interdisciplinary project is supported by a collaborative team with expertise in cancer cell adhesion, mechanobiology, lung immunology and bioinformatics. You will receive training in advanced cell biology, genomics, proteomics and computational network modelling. You’ll be part of a friendly, supportive team committed to scientific excellence and innovation.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in cell biology, molecular biology, biochemistry or cancer biology. Research experience in a wet-lab environment is highly desirable.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants mustmake 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

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cell Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website View Website