Inhibition of the immunophilin family of proteins
Synthesising small molecule inhibitors of immunophilins in bacteria
Immunophilins are a family of peptidyl-prolyl cis-trans isomerases that are present in bacterial pathogens. The immunophilins are involved in protein folding and are important in maintaining protein stability and function, with many studies showing that immunophilins are needed for the proper function of virulence determinants.
In this project, we are investigating a series of small molecule inhibitors that can prevent immunophilin function in bacteria and interfere with virulence and the capacity to cause disease.
We are focused on the intrinsically antibiotic resistant bacteria, Burkholderia pseudomallei, which is the causative agent of melioidosis and has a fatality rate of up to 15 per cent in Northern Australia.
Our main goal for this project is to screen small molecule inhibitors of immunophilins to test the ability of these inhibitors to reduce bacterial virulence in models of infection.
Our research team lead for this project is Dr Mitali Sarkar-Tyson, a research fellow within UWA’s School of Biomedical Sciences. We are collaborating with Professor Ulrike Holzgrabe from the University of Würzburg and Professor Tim Atkins from the Defence Science Technology Laboratories in the United Kingdom. We have also received significant funding from the Defence Material Transfer Centre in Australia, the Defence Science Technology Laboratories in the UK, and the European Union’s North Atlantic Treaty Organization.
Research for PhD students is available in the areas of bacterial pathogenesis and immunity for this project.
PhD students require a bachelor’s in microbiology and immunology, and an honours degree in microbiology or related disciplines, such as molecular biology, biochemistry, chemistry or genetics.
Students who have a master’s should have completed the degree in a related discipline area such as pharmacy, biotechnology or infectious diseases.
If you would like to read more about this project, see below:
- Development, synthesis and structure–activity-relationships of inhibitors of the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and Burkholderia pseudomallei. Florian Seufert, Maximilian Kuhn, Michael Hein, Matthias Weiwad, Mirella Vivoli, Isobel H Norville, Mitali Sarkar-Tyson, Laura E Marshall, Kristian Schweimer, Heike Bruhn, Paul Roesch, Nicholas J Harmer, Christoph A Sotriffer, Ulrike Holzgrabe - Bioorganic & medicinal chemistry, 2016 24: 5134-5147.
- Reimer A, Seufert F, Weiwad M, Ebert J, Bzdyl NM, Kahler CM, Sarkar-Tyson M, Holzgrabe U, Rudel T, Kozjak-Pavlovic V. (2016). Inhibitors of macrophage infectivity potentiator-like PPIases affect neisserial and chlamydial pathogenicity. Int J Antimicrob Agents. 2016 Oct;48(4):401-8.
- Norville IH, Harmer NJ, Harding SV, Fischer G, Keith KE, Brown KA, Sarkar-Tyson M, Titball RW. (2011). A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence. Infect Immun. 2011 Nov;79(11):4299-307.
Contact Dr Mitali Sarkar-Tyson
Send an enquiryMitali.email@example.com
L Block, Queen Elizabeth II Medical Centre, Hospital Avenue Nedlands Western Australia 6009