How does myosin 10 contribute to filopodia formation and stability?

Summary

How do cells make filopodia? Filopodia are thin protrusions that act as pathfinders in cell migration, helping cells to sense where to go, and pulling cells through the extracellular matrix, especially important in driving cancer cell metastasis.

We know that myosin 10 (Myo10) is essential for filopodial formation. However, we do not understand why. We have a limited understanding of its structure and how it is activated and then able to drive filopodial formation. We do not know how it is organised within filopodial tips and helps the tips of filopodia to stick to the extracellular matrix.

A combination of structural biology and imaging approaches will help answer these questions. The project will train you to express and purify proteins using the baculovirus system, and then use CryoEM to determine the structure of Myo10 and find out how the motor and tail of this myosin interact to keep it switched off until needed. It will train you in super-resolution imaging (dSTORM) and in correlative fluorescence and cryo-electron tomography to ‘see’ the myosin inside the filopodia, to reveal how it is organised. By the end of the PhD, we hope to gain new insight into how Myo10 makes filopodia.

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