In a HFSP-funded project, the researcher will develop intracellular nanotools that push the limits of fluorescence microscopy and cryo-Electron Tomography to time-resolve fundamental mechanisms in cell growth. We are leading this project in collaboration with D. Castaño-Díez (Uni. Basel, Switzerland) and A. de Marco (Monash Uni., Australia).
Understanding the molecular mechanisms that drive life (and those that lead to death) requires structural characterization of the protein machinery sustaining the biology of the cell. Ideally, experimental evidences should be obtained at atomic resolution and in a totally physiological context. However, historically, structural biology has been largely centered around in vitro approaches, which provide high-resolution measurements but with poor physiological relevance.
In the past, our lab combined cell engineering and advanced live-cell imaging to develop a new method of live-cell structural biology. Our approach allowed visualizing the architecture of protein complexes directly in living cells and thus we are now capable of solving key questions in cell biology that were not accessible by other techniques (Picco et al, 2017, Cell; Irastorza-Azcarate et al, 2019, Structure). However, our approach is still limited to measurements with 2 nm precision.
We recently received a HFSP grant to continue pushing the limits of microscopy to investigate molecular structures in the cell. In this project we will develop a new method that allows us to resolve molecular structures with Å resolution by using intracellular nanotools and Correlative Light-Electron Microscopy (CLEM). We would like to incorporate a researcher that boosts this line of research and that complements our expertise in the fields of protein engineering, optical physics, quantitative live-cell imaging and/or image analysis. The project will be carried out in tight collaboration with the groups of Daniel Castaño-Díez (Uni. Basel, Switzerland) and Alex de Marco (Monash Uni., Australia). The researcher is expected to visit these labs for short periods and to help us investigating molecular mechanisms the sustain cell growth.
More information can be obtained in our web page: www.gallegolab.org
Picco, A., Irastorza-Azcarate, I., Specht, T., Böke, D., Pazos, I., Rivier-Cordey, A-S., Devos, D.P., Kaksonen, M., Gallego, O., (2017) “The in vivo architecture of the exocyst provides structural basis for exocytosis.” Cell 168, 400-412.e18. Irastorza-Azcarate, I., Castaño-Díez, D., Devos, D. P., and Gallego, O., “Live-cell structural biology to solve biological mechanisms: the case of the exocyst” Structure. 27, 886-892.
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