Super resolution analysis of basement membrane remodelling and microenvironment signalling in pancreatic cancer.

About the Project

Using cutting-edge super-resolution imaging and cell-microenvironment models, this project explores how the ECM shapes tumour growth and could reveal new ways to target cancer. We will discover how tiny changes in the structure of the basement membrane can influence how pancreatic cancer cells behave and communicate with their surroundings.

Pancreatic cancer is one of the most challenging solid tumours to treat, in part because it develops within a uniquely dense and highly organised extracellular matrix (ECM). This physical environment does far more than support tumour cells; it actively shapes their behaviour, interactions, and ability to recruit stromal and immune cells. Understanding how the ECM controls these processes is becoming increasingly important for identifying new therapeutic opportunities, and technologies that allow us to visualise and manipulate the matrix are opening exciting avenues for discovery. This project offers a chance to explore these emerging ideas first-hand, using state-of-the-art imaging to reveal how nanoscale ECM organisation can influence cell behaviour and microenvironmental responses.

Among the primary regulators of basement membrane structure are laminins, a family of heterotrimeric ECM proteins that provide scaffolding and signalling cues. Laminin 332, in particular, is abundant in pancreatic cancer and contributes to the progression, invasiveness, and chemoresistance of the disease. Our team has identified a lesser-known laminin-related protein LaNt α31, which lacks the ability to form conventional laminin trimers but retains the domain responsible for laminin-laminin interactions. We have discovered that LaNt α31 remodels laminin-rich matrices, alters cancer-cell shape and adhesion, and dramatically suppresses tumour formation in an in vivo model. Some of these changes occur even when non LaNt α31 expressing cells are seeded onto an ECM deposited by LaNt-expressing cells, suggesting that the physical structure of the matrix itself is the driver of tumour-microenvironment signalling.

Building on this foundation, the PhD project will investigate how LaNt α31 alters basement membrane architecture at the nanoscale and how these structural changes influence cancer-stromal communication. Using super-resolution microscopy (such as STORM and SIM), the student will quantify alterations in laminin organisation, fibre geometry, and integrin clustering in matrices with or without LaNt α31. Alongside this, the student may choose to explore how these structural differences affect stromal activation, angiogenic cues, or immune-cell behaviours using co-culture, 3D matrix models, chicken egg (CAM) or transgenic mouse models. There is flexibility throughout to tailor the project towards ECM biophysics, tumour-cell signalling, or the microenvironment depending on the student’s interests, while still contributing to a cohesive overall research narrative.

The student will receive comprehensive training in advanced imaging, cell and molecular biology, ECM analysis, and quantitative image processing. Additional training opportunities include RNA-seq data interpretation, 3D tissue culture, and matrix proteomics, depending on the chosen direction. The project will be embedded within an active ECM and cancer biology research environment, with opportunities for collaboration across microscopy facilities, cancer research groups, and matrix biology teams at Liverpool.

In the first year, the student will focus on training, establishing cell models, and learning super-resolution techniques. Years two and three will involve onward development of the chosen research direction, generation of publishable datasets, and integration of imaging with functional biological assays. By the end of the project, the student will have developed cutting-edge technical skills and a deep conceptual understanding of how basement membrane structure shapes cancer progression.

Express your interest by email to khamill@liverpool.ac.uk and we will schedule a time to chat.

Note this is a not-funded PhD at this time, so please indicate if you have funding secured and/or options for where you/we can apply.