Our Research
Cell division
HeLa cell rounding up and dividing - Actin cytoskeleton is labelled in green and DNA in red
When they divide, cells undergo a series of dramatic shape changes. They round up as they enter mitosis, before elongating and dividing in two. Cells also change their mechanical properties as they divide allowing them to exert force against their environment (Taubenberger 2020). These shape and mechanical changes are controlled by dynamic re-organisation of the actin cytoskeleton and cell-substrate adhesion throughout cell division.
We are investigating how the cell shape and mechanics are regulated during cell division. To do this, we take a multidisciplinary approach combining cell biology and imaging with biophysical techniques, such as atomic force microscopy, to measure cells’ mechanical properties. We are studying cell division mechanics in the context of both single cells and in epithelial tissues, where cells must undergo change shape while maintaining cell-cell adhesion to preserve tissue integrity. We are using epithelial monolayer systems to understand the forces applied when cells divide within proliferative tissues.
Tumour initiation
Cell division in tumoroids- Actin is labelled in red, tubulin in green & DNA in blue (Image by Max Williamson)
Cancer begins with an oncogenic mutation within a single cell. We are studying how the activation of oncogenic signalling pathways affects cell shape and mechanics, with a particular focus on the Ras family of oncogenes. Our published work (Matthews 2020, Ganguli 2023) showed how the activation of Ras oncogenes changes cell shape and mechanics during cell division. This helps cancer cells divide in confined conditions as well as altering the angle of cell division, leading to a breakdown of normal tissue structure. We are now investigating the molecular mechanisms by which Ras oncogenes perturb the actin cytoskeleton to promote tumour formation and ultimately, invasion and metastasis.
Pancreatic Cancer
Pancreatic ductal carcinoma (PDAC) has a poor survival rate and very few treatment options available for patients. 90% of PDAC tumours are driven by mutations in the KRAS oncogene. We want to understand how oncogenic KRAS signalling alters the cytoskeleton to promote cell division and invasion within the PDAC tumour microenvironment. We also investigating how cell shape and mechanics affect the response of PDAC cells to therapy, including cell-cycle targeting chemotherapies as well as new inhibitors that directly target mutant KRAS. We hope to identify molecular mechanisms that underlie intrinsic and acquired resistance to PDAC cancer therapy, which can help to inform smarter treatments in the future.
Our Research is funded by:
