Force generation and sensing at molecular level
This 4-year PhD studentship is offered in Dr Maxim Molodtsov’s Group based at the Francis Crick Institute (the Crick).
This project is for students with background in physics/engineering/math who want to make an important impact in life sciences.
Mechanical forces generated at molecular level are required for cells to grow and divide. Cell growth, differentiation and division require physical rearrangements of the cell interior at scales much larger than the size of individual molecules driving these rearrangements. In order to achieve this, action of many motor and non-motor proteins must be precisely coordinated. Mutations in these molecules and other factors that lead to disorganization cause disorders in development and disease. Our goal is to understand the basis of how this coordination is achieved mechanistically.
Our group has strong expertise in investigating how forces are generated and transduced at the tips of the microtubules – slender fibrils that comprise the backbone of the cytoskeleton and constitute the essential element required for the cell growth and cell division . Using optical tweezers and purified proteins, we have previously discovered mechanisms how microtubules are rearranged by forces generated at their tips . However, how these forces are integrated in live cells is a fundamental outstanding question. The progress in this field is currently limited by physical tools required to interrogate specific force generating and sensing mechanisms in cells.
In this project, we will develop new tools for applying and measuring forces in live cells using microelectromagnetics. This technology allows manipulating small objects on the submicrometer scale . The project will consist of few steps. First, we will perform computer simulations to identify the best ways to manipulate submicron size magnetic objects by external magnetic fields at nanoscale. Once successful strategy is chosen, we will create a prototype of an instrument for manipulation and test it in artificial system. Finally, we will apply it to measure forces in live cells and investigate the contribution of individual force generating mechanisms into the rearrangement of the cytoskeleton. Our approach will also have impact in other areas of cell biology and life sciences and have broad biological applications.
Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2019 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) MARCH 19 2019. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
1. McIntosh, J. R., Molodtsov, M. I. and Ataullakhanov, F. I. (2012)
Biophysics of mitosis.
Quarterly Reviews of Biophysics 45: 147-207. PubMed abstract
2. Molodtsov, M. I., Mieck, C., Dobbelaere, J., Dammermann, A., Westermann, S. and Vaziri, A. (2016)
A force-induced directional switch of a molecular motor enables parallel microtubule bundle formation.
Cell 167: 539-552 e514. PubMed abstract
3. Lee, H., Purdon, A. M. and Westervelt, R. M. (2004)
Manipulation of biological cells using a microelectromagnet matrix.
Applied Physics Letters 85: 1063-1065.