Debnath Ghosal - Bio21 Institute

Debnath Ghosal - Bio21 Institute

Location: 
Online
Start Time: 
Wed, 07/04/2021 - 1:00pm
End Time: 
Wed, 07/04/2021 - 2:00pm

WEHI Wednesday Seminar hosted by Associate Professor Isabelle Lucet and Dr Onisha Patel, ACRF Chemical Biology division

 

Debnath Ghosal, PhD

Senior Lecturer and NHMRC Emerging Leadership Fellow, Department of Biochemistry & Pharmacology, Bio21 Molecular Science & Biotechnology Institute, The University of Melbourne


 

In Situ Structures of Bacterial Toxin Delivery Systems by Electron Cryotomography

 

Online via Slido and enter code #WEHIWEDNESDAY

Including Q&A session



Bacteria harbour at least 10 different types of secretion systems to export various virulence factors including small molecules, proteins and DNA across the bacterial cell envelope. These specialized nanomachines are attractive drug targets, however structural studies of these molecular machines are daunting because these are often multi-megadalton flexible complexes that span the entire length of the cell envelope and attempts to purify them disrupt their structure and composition. We harness the unique power of electron cryotomography and subtomogram averaging method to investigate these molecular machines in situ, in their native context, at macromolecular resolution.

 

In my talk, I will discuss how we used electron cryotomography and subtomogram averaging to investigate the molecular architecture and biogenesis of the bacterial Type IV Secretion System (T4SS) utilized by the human pathogen Legionella pneumophila. Our detailed structural analysis mapped the location of the core and accessory components and revealed the molecular organization of the Legionella T4SS. An in-depth examination of the biogenesis pathway revealed that the T4SS complex assembles by an innovative “outside-inside” mechanism.

 

Debnath Ghosal is a senior lecturer and an NHMRC Emerging Leadership Fellow at the Department of Biochemistry & Molecular Biology, University of Melbourne. Debnath received his PhD degree in structural biology from the MRC Laboratory of Molecular Biology (University of Cambridge), where he worked with Prof Jan Löwe on bacterial cell division associated proteins. Fascinated by the unique power of electron cryotomography in resolving three dimensional structures of protein complexes inside 'living' cells, he then joined Prof Grant Jensen’s laboratory for his postdoctoral training at Caltech. There he investigated the struc ture and function of bacterial toxin delivery systems. Debnath established his own laboratory at University of Melbourne in 2020. His group is working on large protein complexes that are important for pathogenesis using cryoEM methods.