Imaging Life 2020: Invited speakers and programme
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Prof. Maddy Parsons
King’s College London Imaging cytoskeletal dynamics in invading cancer cells Cells have to dynamically adapt their shape to respond to changes in the extracellular environment. This is a key feature in both homeostatic situations such as embryonic development and differentiation as well diseases such as cancer cell invasion. Changes in cell shape require dynamic reorganisation of the F-actin cytoskeleton. Fascin is a highly conserved F-actin bundling protein that controls cytoskeletal dynamics, but is also highly upregulated in human cancers, correlates with poor clinical prognosis and metastasis. However, the mechanisms governing spatial, temporal and functional regulation of fascin remain poorly understood. We have developed a range of different advanced microscopy methods to address this question and through this, we have shed new light on the molecular control of fascin dynamics and activity within living tumour cells. Our data helps to provide new insight into how cells adapt to their environment and potential routes for therapeutic development to halt cancer progression. |
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Dr. Paula da Fonseca
University of Cambridge Cryo-EM of proteasomes: from fundamental studies to drug discovery Proteasomes are protease complexes essential in all eukaryotes, both for their role in proteostasis and in the regulation of a wide range of fundamental cellular processes, including cell cycle progression, DNA repair and immune responses. Proteasomes are already well-established targets for cancer therapy, and their inhibition is being explored for an increasing range of other therapeutic usages. However, the detailed mechanisms of proteasome function and regulation are still not fully characterised. We use cryo-EM to address these issues, particularly focusing on the analysis of human complexes. Additionally, we explore cryo-EM as a tool for the discovery and development of new therapeutic drugs. In this context, our cryo-EM analysis contributed to the validation of the Plasmodium falciparum proteasome as a potential antimalarial target, and to guide the development of new highly specific inhibitors. Our work highlights advantages of cryo-EM for such studies, which usage expands beyond proteasome research. |
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Dr. Núria Gavara
Queen Mary University of London Bio-AFM is the new black in biomedical sciences In the last years it has been acknowledged that cellular fate and behaviour are greatly influenced by the mechanical properties of the cells, as well as their environment. The mechanical characterisation of cells and tissues using AFM is no longer a niche technique by those working on biophysical sciences. Instead, it is slowly becoming another method within the toolkit of techniques typically boasted in high-impact papers on basic cell biology or biomedical sciences. While this constitutes a fantastic opportunity for those long working on the field, it has also posed exciting challenges, which i will convey during the talk. From an instrumental side, a massive push has been aimed at building AFMs in combination with advanced light microscopy and super-resolution setups, and to increase the overall user-friendliness of AFM operation. From an experimental and modelling side, new protocols acknowledge the complexity of cellular mechanics, moving beyond the simplest hertzian models at quasi-static regimes. In addition, AFM is morphing into a high-throughput method, thus stressing the need for fully-automated but reliable pipelines to extract mechanical parameters from the thousands of acquired force-distance curves. Finally, the advent of big data and machine learning approaches for disease diagnostic opens new avenues, but raises questions on how we can turn AFM into a more 'multiplex' technique to further its impact in life sciences and biomedicine research. |
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We would like to thank the following companies for their sponsorship: