Dr Alastair Stewart, Head of Structural Biology Laboratory

"For me, I love the discovery process. It's innate within us; it's the same reason we took to the ocean to explore our world, and then sent 12 others to step on the moon. Seeing the machinery of life is a great privilege that I’m very lucky to have, and getting to tell these stories to the rest of the world is a fantastic feeling,"

- Dr Alastair Stewart

Dr Alastair Stewart

Head, Structural Biology Laboratory

Research overview

Key Research Areas

  • Membrane protein function
  • Cyro-Electron Microscopy

Research Overview

Dr Stewart’s research aims to understand how membrane proteins function. His lab uses a complementary spectrum of structural, biochemical and cellular methods, especially cryo-electron microscopy, to probe the inner workings of a range of molecular targets.

research projects

There are 2 key projects underway in the Structural Biology Laboratory

1. ATP synthase function

ATP synthases are ubiquitous protein complexes that couple ATP synthesis/hydrolysis with proton translocation via a rotary catalytic mechanism. Our lab is using cryo-Electron Microscopy to generate high resolution information on ATP synthase under a range of conditions, including those inhibited by small molecules such as antibiotics.

2. Transporter function

The SLC22s are family are membrane proteins that facilitate the movement of endogenous and exogenous compounds across cell membranes. Because they can transport a vast number of pharmacological agents, members of the SLC22 family are referred to as “drug transporters” and have key implications for drug disposition. We are generating high resolution information on a range of SLC22 transporters bound to a range to small molecules, to understand the molecular basis of transport and inhibition of clinically relevant compounds.

FUNDING

  • NHMRC Investigator Grant 2023-2027
  • NHMRC Career Development Fellowship 2019-2022
  • NHMRC Project Grant 2018-2020 (CIA)
  • NHMRC Project Grant 2018-2020 (CIB)
  • NHMRC Early Career Fellowship - Peter Doherty Biomedical 2015-2018

laboratory members & collaborators

Current members:

Dr Meghna Sobti, Senior Research Officer (2017-)

Yi Zeng, PhD student (2021-)

Past members:

Dr Emily Furlong (2021-2022: now a Lecturer at ANU, Canberra)

Dr James Walshe (2019-2021: now in the Crammer Lab, Max Planck Institute, Göttingen)

Cameron Ding (2018: now a medical student UQ, Brisbane)
Dr Jessica Chaston (2016-2018)

Collaborators

Prof Carol Robinson, University of Oxford

Prof Hiroyuki Noji, Tokyo University

Prof Richard Berry, University of Oxford

publication highlights

  1. Sobti M, Zeng YC, Walshe JL, Brown SHJ, Ishmukhametov R & Stewart AG (Jan, 2023) 'Changes within the central stalk of E. coli F1Fo ATP synthase observed after addition of ATP' Communications Biology; https://doi.org/10.1038/s42003-023-04414-z
  2. Sobti M, Ueno H, Noji H & Stewart AG (Aug, 2021) The six steps of the complete F1-ATPase rotary catalytic cycle' Nature Communications; https://doi.org/10.1038/s41467-021-25029-0
  3. Chen I, Pant S, Wu Q, Cater RJ, Sobti M, Vandenberg RJ, Stewart AG, Tajkhorshid E, Font J & Ryan RM (Feb, 2021) 'Glutamate transporters have a chloride channel with two hydrophobic gates' Nature; https://doi.org/10.1038/s41586-021-03240-9
  4. Sobti M, Walshe JL, Wu D, Ishmukhametov R, Zeng YC, Robinson CV, Berry RM & Stewart AG (May, 2020) 'Cryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch' Nature Communications; https://doi.org/10.1038/s41467-020-16387-2
  5. Sobti M, Ishmukhametov R, Bouwer JC, Ayer A, Suarna C, Smith NJ, Christie M, Stocker R, Duncan TM & Stewart AG (Mar, 2019), 'Cryo-EM reveals distinct conformations of E. coli ATP synthase on exposure to ATP', eLife; https://doi.org/10.7554/eLife.43864
  6. Chorev DS, Baker LA, Wu D, Beilsten- Edmands V, Rouse SL, Zeev-Ben-Mordehai T, Jiko C, Samsudin F, Gerle C, Khalid S & Stewart AG, Matthews SJ, Grünewald K, Robinson CV (Nov, 2018), 'Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry', Science; https://doi.org/10.1126/science.aau0976
  7. Sobti M, Smits C, Wong ASW, Ishmukhametov R, Stock D, Sandin S & Stewart AG (Dec, 2016) 'Cryo-EM structures of the autoinhibited E. coli ATP synthase in three rotational states', eLife; https://doi.org/10.7554/eLife.21598
  8. Chaston JJ, Smits C, Aragao D, Ahsan B, Sandin S, Molugu SK, Molugu SK, Bernal RA, Stock D & Stewart AG (Mar 2016), 'Structural and functional insights into the evolution and stress adaptation of type II chaperonins', Structure; https://doi.org/10.1016/j.str.2015.12.016
  9. Stewart AG, Lee LK, Donohoe M, Chaston JJ & Stock D (Feb, 2012), 'The dynamic stator stalk of rotary ATPases', Nature Communications; https://doi.org/10.1038/ncomms1693
  10. Lee LK*, Stewart AG*, Donohoe M, Bernal RA & Stock D (Mar, 2010), 'The structure of the peripheral stalk of T. thermophilus H+-ATPase/synthase', Nature Structural & Molecular Biology; https://doi.org/10.1038/nsmb.1761
Acknowledgement of Country

The Victor Chang Cardiac Research Institute acknowledges the traditional custodians of the land, the Gadigal of the Eora nation, on which we meet, work, and discover.
Our Western Australian laboratories pay their respect to the Whadjuk Noongar who remain as the spiritual and cultural custodians of their land.

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