[3dem] Postdoctoral position: cryo-EM of membrane protein complexes in Toronto

Tue Mar 1 07:26:08 PST 2022

Dear Colleagues,

I have a postdoctoral position available in my laboratory in Toronto. The position is ideal for a candidate with a strong interest in biophysical methods who wants to deepen their understanding of cryo-EM and membrane protein structure and function. Previous experience with cryo-EM is not required but would, of course, be helpful.

Please contact me if interested.

Sincerely,
John Rubinstein

p.s. I hope this is not a duplicate message and apologize if it is. My previous attempt to send a job ad to the 3DEM list appears not to have been delivered.

Background information:

The Rubinstein Laboratory at The Hospital for Sick Children in Toronto uses and develops cryo-EM methods to study large and dynamic membrane protein complexes involved in bioenergetics. Current research directions include studies of oxidative phosphorylation (1–6), particularly in the context of mycobacterial infection, and the structure and regulation of proton pumping V-type ATPase (7–11), particularly in the contexts of neurobiology and lysosomal biology. We are developing new ways of looking at membrane protein complexes to understand how their dynamics control their function. Our method development efforts include work on specimen preparation (12–14), imaging (15), and image analysis (16,17). We have close academic collaborations related to bioenergetics, medicinal chemistry, and computer science. We also have research agreements with start-up companies and a large instrument manufacturer, which provides us with access to prototype instruments not found elsewhere.

The ideal candidate should have or be about to obtain a PhD where they used biophysical methods to study biological molecules such as proteins or lipids (e.g. cryo-EM, X-ray crystallography, NMR spectroscopy, or other spectroscopy methods). Comfort with scientific computing is an advantage. They should have an interest in both biological structure and cryo-EM methods. They should enjoy working with highly-developed instruments and software but also enjoy developing new experiments where new instruments and/or software may need to be created.

Infrastructure in the laboratory includes outstanding access to cryo-EM screening microscopes (a TF20 with Gatan K2 Summit camera and a soon-to-be-installed Glacios with Falcon 4i camera) and a dedicated data collection microscope (Krios G3i with a Falcon 4i camera). We have numerous commercial specimen preparation devices as well as home-built computer controlled devices (13,14). We also have outstanding access to biophysical, nanofabrication, and cell biology infrastructure.

The Hospital for Sick Children’s Research Institute is located in the heart of downtown Toronto and includes approximately 2,000 researchers, students, postdoctoral fellow, and staff. The Hospital is one of the largest paediatric hospitals in the world and was ranked the top paediatric health care centre in the world by Newsweek's 2021 World's Best Hospitals list. The Hospital and Research Institute are affiliated with the University of Toronto, a top research University. Toronto is Canada’s largest city and North America’s 4th largest city (after Mexico City, New York, and Los Angeles). It is one of the world’s most multicultural centers with vibrant arts and culture communities. Despite its size, it is also one of North America’s safest cities.

Please contact john.rubinstein at utoronto.ca if interested.

References:
1.         Guo, H., Bueler, S. A. & Rubinstein, J. L. Atomic model for the dimeric FO region of mitochondrial ATP synthase. Science 358, 936–940 (2017).
2.         Moe, A., Di Trani, J., Rubinstein, J. L. & Brzezinski, P. Cryo-EM structure and kinetics reveal electron transfer by 2D diffusion of cytochrome c in the yeast III-IV respiratory supercomplex. Proc. Natl. Acad. Sci. 118, e2021157118 (2021).
3.         Wiseman, B. et al. Structure of a functional obligate respiratory supercomplex from Mycobacterium smegmatis. Nat. Struct. Mol. Biol. 25, 1128–1136 (2018).
4.         Yanofsky, D. J. et al. Structure of mycobacterial CIII2CIV2 respiratory supercomplex bound to the tuberculosis drug candidate telacebec (Q203). eLife 10, e71959 (2021).
5.         Guo, H. et al. Structure of mycobacterial ATP synthase with the TB drug bedaquiline. Nature 589, 143–147 (2021).
6.         Guo, H. & Rubinstein, J. L. Structure of ATP synthase under strain during catalysis. bioRxiv 2022.01.24.477618 (2022) doi:10.1101/2022.01.24.477618.
7.         Zhao, J., Benlekbir, S. & Rubinstein, J. L. Electron cryomicroscopy observation of rotational states in a eukaryotic V-ATPase. Nature 521, 241–245 (2015).
8.         Mazhab-Jafari, M. T. et al. Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase. Nature 539, 118–122 (2016).
9.         Abbas, Y. M., Wu, D., Bueler, S. A., Robinson, C. V. & Rubinstein, J. L. Structure of V-ATPase from the mammalian brain. Science 367, 1240–1246 (2020).
10.       Vasanthakumar, T., Keon, K. A., Bueler, S. A., Jaskolka, M. C. & Rubinstein, J. L. Coordinated conformational changes in the V1 complex during V-ATPase reversible dissociation. bioRxiv 2021.11.09.467972 (2021) doi:10.1101/2021.11.09.467972.
11.       Tan, Y. Z. et al. Structure of mammalian V-ATPase with the TLDc domain protein mEAK7 bound. bioRxiv 2021.11.03.466369 (2021) doi:10.1101/2021.11.03.466369.
12.       Marr, C. R., Benlekbir, S. & Rubinstein, J. L. Fabrication of carbon films with approximately 500 nm holes for cryo-EM with a direct detector device. J Struct Biol 185, 42–47 (2014).
13.       Rubinstein, J. L. et al. Shake-it-off: A simple ultrasonic cryo-EM specimen preparation device. Acta Cryst D75, 632125 (2019).
14.       Tan, Y. Z. & Rubinstein, J. Through-grid wicking enables high-speed cryoEM specimen preparation. Acta Cryst D, 10.1101/2020.05.03.075366 (2020).
15.       Guo, H. et al. Electron-event representation data enable efficient cryoEM file storage with full preservation of spatial and temporal resolution. IUCrJ 7, 860–869 (2020).
16.       Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: Algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
17.       Rubinstein, J. L. & Brubaker, M. A. Alignment of cryo-EM movies of individual particles by optimization of image translations. J. Struct. Biol. 192, 1–11 (2015).

— 
John Rubinstein
Molecular Medicine Program
The Hospital for Sick Children
686 Bay Street, Rm. 20-9705
M5G 0A4
(+001) 416-813-7255
https://urldefense.proofpoint.com/v2/url?u=http-3A__www.rubinsteinlab.org&d=DwIGaQ&c=-35OiAkTchMrZOngvJPOeA&r=L7-zyQ-04fFCMRqzLIOnx7H0exGZHwIQe_wMPuY600I&m=ukU0S02HBjePN7Aoy-FQslUgagLAOQh69v0wytFCb0AJHp_c4OCMXJem8M_3FWUN&s=9rkDd5JHODJJdQmq7ZULsXt4aPRQg95Fo8n-gM6PyjM&e= 