Rouiller laboratory: Understanding how molecular machines function through cryo-electron microscopy

Researcher

Research Overview

The Rouiller lab utilises cryo-electron microscopy as a structural biology approach to study how molecular machines function. Using the single particle and tomography techniques, we determine the structures of molecular machines "in action" along their biological pathways. The systems we study include:

  • The AAA ATPase p97 activity in health and disease: p97 is an essential protein for cell homeostasis that plays a major role in multiple cellular functions, including membrane. Our studies aim at understanding how p97 perform its functions at the molecular level in order to develop inhibitors to be used for the treatment of cancer and multisystem proteinopathy (e.g. Inclusion Body Myopathy with early-onset Paget disease and Frontotemporal Dementia- IBMFD and Amyotrophic Lateral Sclerosis- ALS).
  • Transporters: We are studying the molecular mechanism that drive transport of substrates, proteins and ions across membranes. The systems we are studying include Anthrax toxins, ABC transporters (e.g. the MalFGK2 transporter), RND transporters (e.g. the mycolic acid transport from Mycobacterium tuberculosis) and ion transporters (e.g. the mechanosensitive ion channel TACAN).
  • Viral glycoproteins (e.g. Influenza Hemagglutinin) involved in host pathogen interactions. We are interested in the structural implication these proteins for vaccine development and immune response.

Rouiller lab

Staff

Dr Sudipta Bhattacharyya, Postdoctoral Fellow

Dr Mohsen Kazemi, Postdoctoral Fellow

Ms Sepideh Valimehr, PhD candidate

Ms Nazanin Mohebali, PhD candidate

Mr Ian Noel Costas Cancelas, MSc candidate (McGill University)

Collaborators

Dr David Ascher, University of Melbourne, AUSTRALIA

Professor Rikard Blunck, Université de Montréal, CANADA

Professor Ella Bossy-Wetzel, University of Central Florida, USA

Dr Till Böcking, University of New South Wales, AUSTRALIA

Professor Franck Duong, University of British Columbia, CANADA

A/Professor Andres Finzi, Université de Montréal, CANADA

Professor Ted Fon, McGill University, CANADA

A/Prof Paul Gooley, University of Melbourne, AUSTRALIA

Dr Slavica Jonic, Sorbonne Université, FRANCE

Dr Helene Khlein, Université de Montréal, CANADA

A/Prof Connie Krawczyk, McGill University, CANADA

Dr Nathalie Landry, Medicago Inc, CANADA

Dr Megan Maher, La trobe University, AUSTRALIA

Dr Justine Mintern, University of Melbourne, AUSTRALIA

Professor Michael Parker, University of Melbourne, AUSTRALIA

Professor Jurgen Sygush, Université de Montréal, CANADA

Professor Leann Tilley, University of Melbourne, AUSTRALIA

Professor Brian Ward, McGill University, CANADA

Dr Nicholas Williamson, University of Melbourne, AUSTRALIA

Professor Helen Zgurskaya, University of Oklahoma, USA

Funding

STEM-M Stimulus Fund - University of Melbourne

Research Opportunities

This research project is available to PhD, Honours students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

For complete list of publications, https://www.ncbi.nlm.nih.gov/pubmed/?term=rouiller+i

Brianne J. Lindsay, Michal Bonar, Kristin Hunt, Alex Makarkov, Sabrina Chierzi, Connie Krawczyk, Nathalie Landry, Brian Ward, Isabelle Rouiller. The Morphological Characterization of Plant Generated Virus-Like Particles by Electron Microscopy for Protection against the Influenza Virus. Vaccine 2018; 36(16):2147-2154 https://www.sciencedirect.com/science/article/pii/S0264410X18303165?via%3Dihub

Lucien Fabre, Huan Bao, Franck Duong, Isabelle Rouiller. Negative Stain Single-particle EM of the Maltose Transporter in Nanodiscs Reveals Asymmetric Closure of MalK2 and Catalytic Roles of ATP, MalE, and Maltose. J Biol Chem 2017; 292 (13): 5457-5464 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392688/

Lucien Fabre, Eugenio Santelli, Driss Mountassif, Annemarie Donoghue, Aviroop Biswas, Rikard Blunck, Dorit Hanein, Niels Volkmann, Robert Liddington, Isabelle Rouiller. Structure of anthrax lethal toxin prepore complex suggests a pathway for efficient cell entry. J Gen Physiol 2016; 148 (4): 313-324 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037343/pdf/JGP_201611617.pdf

Driss Mountassif, Lucien Fabre, Yusef Zaid, Dalhia Halawani, Isabelle Rouiller. Cryo-EM of the pathogenic VCP variant R155P reveals long-range conformational changes in the D2 ATPase ring. Biochem Biophys Res Commun 2015;468(4):636-41 https://www.sciencedirect.com/science/article/pii/S0006291X15308731?via%3Dihub

Research Projects



Faculty Research Themes

Neuroscience, Infection and Immunology, Cancer

School Research Themes

Biomedical Neuroscience, Infection & Immunity, Cancer in Biomedicine, Cellular Imaging & Structural Biology



Key Contact

For further information about this research, please contact Associate Professor Isabelle Rouiller

Department / Centre

Biochemistry and Molecular Biology

Unit / Centre

Rouiller laboratory: Understanding how molecular machines function through cryo-electron microscopy

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