How kinesins drive microtubule lattice plasticity and dynamics
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project:
Inside almost every cell in your body is a miniscule railway system, built from microtubules, which are themselves built by plugging together short sections of rail, called tubulins. Recently and unexpectedly, we have found that the engines of this molecular railway (kinesin molecular
motors) have previously-unappreciated effects on their microtubule rails. We find that when kinesins grip their microtubule rails, they expand the spacing between neighbouring tubulins and at the same time dramatically stabilise their otherwise-unstable structure. Our findings show that at least in principle, microtubules can sense whether or not kinesins are moving along them, and respond by changing their structure and stability.
This project aims to discover the biological implications of these findings, by asking (1) whether the different microtubules respond in different ways to different kinesins, (2) how microtubule-directed drugs change the ability of microtubules to sense kinesin binding.
By addressing these questions, we expect to contribute to the Applied Biomedical Technologies research theme of MRC/NPIF strategy. We will develop new open source super resolution optical microscopy hardware and software that enables the combination of microfluidics with single molecule imaging for the quantitation of microtubule dynamics. In addition, we will develop new tubulins that carry a single, bright, photostable fluorescent reporter, and make these new tubulins available to the community. We expect both these activities, ultimately, to facilitate the discovery and optimisation of new tubulin-directed therapeutic agents.
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.
Project:
Inside almost every cell in your body is a miniscule railway system, built from microtubules, which are themselves built by plugging together short sections of rail, called tubulins. Recently and unexpectedly, we have found that the engines of this molecular railway (kinesin molecular
motors) have previously-unappreciated effects on their microtubule rails. We find that when kinesins grip their microtubule rails, they expand the spacing between neighbouring tubulins and at the same time dramatically stabilise their otherwise-unstable structure. Our findings show that at least in principle, microtubules can sense whether or not kinesins are moving along them, and respond by changing their structure and stability.
This project aims to discover the biological implications of these findings, by asking (1) whether the different microtubules respond in different ways to different kinesins, (2) how microtubule-directed drugs change the ability of microtubules to sense kinesin binding.
By addressing these questions, we expect to contribute to the Applied Biomedical Technologies research theme of MRC/NPIF strategy. We will develop new open source super resolution optical microscopy hardware and software that enables the combination of microfluidics with single molecule imaging for the quantitation of microtubule dynamics. In addition, we will develop new tubulins that carry a single, bright, photostable fluorescent reporter, and make these new tubulins available to the community. We expect both these activities, ultimately, to facilitate the discovery and optimisation of new tubulin-directed therapeutic agents.
