**PLEASE NOTE – the deadline for requesting a funding pack from Darwin Trust has now passed and completed funding applications must be submitted to Darwin Trust by 19th January. We can still accept applications for this project from self-funding students.
Cells have intracellular organelles such as centrosomes, mitotic spindle and cilia, which are made from microtubules. They play key roles in cell proliferation, genome integrity and signalling and motility. Controlling the microtubule architecture and size of these organelles is essential for cell function and division. The microtubule cytoskeleton is highly dynamic, with the plus ends growing and shrinking rapidly. The minus ends of microtubules are modestly dynamic, and embedded in the centrosome. The centrosome also acts a signalling and protein interaction hub for regulators of microtubule dynamic regulators. The regulation of minus ends is poorly understood, despite its importance in controlling spindle flux, length of organelles and microtubule nucleation and organization. This raises questions about the regulation of microtubule stability at centrosomes and the role of atypical tubulin isotypes essential for centrosome integrity.
In this project the student use cell biology, biochemical in vitro reconstitution experiments and image analysis to define how microtubule depolymerizing motors and capping proteins recognize the minus ends of microtubules, and how microtubule ends remain dynamic and subject to regulation while connected to centrosomes.
This project enables a motivated Ph.D. student to apply state-of-the-art microscopy and quantitative image analysis, in vitro reconstitution assays, as well as molecular cell biology and biochemical techniques to investigate the molecular properties of microtubules. The student will also use in silico predictors and machine learning algorithms to analyze the assembly of large cytoskeletal assemblies and predict the disease mechanism underlying pathogenic mutations. The successful candidate will be able to choose between several exciting aspects of the project, all of which pose fascinating opportunities for novel discoveries. These results will have strong implications for our understanding of the cell division and organization and for normal biology.
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