We are interested in the spread of cancer, a process called metastasis. Metastasis is responsible for the majority of cancer deaths and there are currently no effective treatments to stop this process. Metastasis is a complex process that involves movement of cancer cells away from the primary tumour, spreading through the blood or lymphatic system and then colonising distant sites in the body. It is this final stage – the colonisation of distant sites – that is our area of research. Cancer cells arriving at new sites often remain dormant for many years as the new site lacks the specific environment to support their growth. These metastatic cells need to acquire new mutations and adaptations, often remodelling their new environment in the process, in order to successfully colonise the new site. How this process happens is the focus of this project.
This project will apply a range of techniques in cell biology and experimental evolution to understand how cancer cells adapt to new environments. One of the key ways that cells interact with their environment is through focal adhesions. Focal adhesions are large, multi-protein complexes that connect the cytoskeleton to the extracellular matrix (ECM) via cell surface integrin molecules. They play a critical role in how cells sense and respond to their environment and their dynamic turnover is essential for both cancer cell migration and for remodelling the ECM. We are interested in the role of post-translational modifications such as SUMOylation in the regulation of focal adhesions.
It is likely that cancer cells will evolve different strategies for interacting with their environment depending on the precise nature of the environment. This project will explore how different strategies for regulating focal adhesions evolve in different types of ECM using experimental evolution techniques.
This project will involve a wide variety of techniques including confocal microscopy and live cell imaging, the use of novel tissue engineering approaches to study metastatic colonisation, experimental evolution approaches including selection experiments, computer modelling approaches such as agent-based models and next generation sequencing techniques such as RNAseq and exome sequencing along with the appropriate bioinformatics analysis.
Web link: https://www.reading.ac.uk/biologicalsciences/about/staff/p-r-dash.aspx