Deciphering structures of bacterial and viral molecular machines that inject toxins into our cells

Research Opportunity
Masters by Research, Master of Biomedical Science
Number of Honour Places Available
2
Number of Master Places Available
2
Department
Biochemistry and Molecular Biology
Location
Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
Dr. Debnath Ghosal debnath.ghosal@unimelb.edu.au +61 3 83448441 Personal web page

Summary Pathogenic bacteria/viruses use specialized “nanomachines” to invade eukaryotic host cells. Our goal is to decipher the structure and function of these molecular machines by electron cryotomography.

Project Details

Bacteria harbour at least nine different types of secretion systems to transfer macromolecules across cellular envelope. These are sophisticated multi-protein nanomachines that secrete myriads of substrates including proteins, nucleoprotein complexes and variety of small molecules and are central to pathogenesis of multiple human diseases. For example, many pathogenic bacteria utilize the Type III Secretion System (T3SS) to cause diseases such as dysentery (Shigella), typhoid (Salmonella), plague (Yersinia) etc. Other human pathogens employ the Type IV Secretion System (T4SS) to mediate gastric cancer (Helicobacter), brucellosis (Brucella), typhus and spotted fevers (Rickettsia), as well as Legionnaires’ disease (Legionella). The T4SS is also associated with the spread of antibiotic resistance, which currently presents a major threat to public health. Therefore, these molecular machines are attractive targets for drug developments to enrich our present repertoire of antibiotics. Structural studies with these molecular machines are extremely challenging due to their large number of components, flexibility and tight integration into the bacterial cell envelope.

Electron cryotomography (cryo-ET) has unrivalled power to visualize the native structure of macromolecules in situ. In recent years, improvement in software, detectors and implementation of improved subvolume averaging methods have allowed us to investigate macromolecules in situ at subnanometer resolution. We are harnessing this unique power of cryo-ET and combining it with correlative light and electron microscopy (CLEM), and Focused Ion Beam (FIB) milling to elucidate the structure and function of different bacterial injection modules at molecular resolution.

For  more information visit here: www.ghosallab.com



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease, Cellular Imaging & Structural Biology



Research Opportunities

Masters by Research, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Biochemistry and Molecular Biology

Research Group / Unit / Centre

Debnath Ghosal laboratory

Research Node

Bio21 Molecular Science and Biotechnology Institute

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