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Multiscale modelling of cancer cell motility: a predictive model of adhesions, blebbing, and spreading
Monday 9th December 2013, 4pm
H.O. Schild Lecture Theatre, Medical Sciences
In the last few years there has been an increasing awareness of the role matrix geometry plays in determining how cells move and cytoskeletal factors required for migration. However, predicting migratory behaviour and the effect of experimental perturbation has proved difficult. To address this issue we developed a computational model that encompasses all key features of migrating cells and changing environments. Using our model, we first set up to identify the intracellular states that will provide fastest cell migration in different matrix geometries. Secondly, we related our model to a highly challenging experimental context; the invasion of cancer cells in vivo. We used the model to predict how cancer cells migrate into the discontinuous collagen matrix that surrounds tumours. Then we predicted the effect of different combinations of kinase inhibitors and integrin depletion in vivo, and in confined matrices in vitro. We used intravital imaging to verify model predictions on bleb-driven migration, and predicted response to biochemical manipulations.
During my undergraduate and masters training in chemical engineering, I worked on systems biology and structural biology, focusing on PPI network of tumour suppressor p73, and mechanistics of SUMOylation. During my PhD in London Research Institute of CRUK, I worked on cancer cell motility. I built a computational model to investigate relations between different cell motility modes, internal cell states, and the extracellular matrix geometry. This body of work will be the topic of my seminar. Currently, I am working in Tissue Mechanics Laboratory within Laboratory of Molecular Cell Biology at UCL. I have recently started this post with the Sir Henry Wellcome Postdoctoral Fellowship for investigating the mechanical regulation of tissue growth. In the following four years, we will be approaching the problem with a combinatorial experimental and computational approach, we will carry out the experiments on Drosophila, and develop computational models at both tissue scale and cellular scales.
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