Solving the native structure of the malaria parasite using cryo-electron microscopy
- Research Opportunity
- PhD students, Masters by Research, Honours students
- Department / Centre
- Biochemistry and Pharmacology
- Location
- Bio21 Molecular Science and Biotechnology Institute
| Primary Supervisor | Number | Webpage | |
|---|---|---|---|
| Professor Leann Tilley | ltilley@unimelb.edu.au | 0383442227 | Personal web page |
| Co-supervisor | Number | Webpage | |
|---|---|---|---|
| A/Prof. Eric Hanssen | ehanssen@unimelb.edu.au | 83442449 |
Summary The proposed project will use cryoEM and molecular biology techniques to study the malaria proteasome to underpin efforts to find potent and specific inhibitors of the proteasome. The project will also solve the structure of mutant and wildtype Pf20S proteasome to understand the molecular basis of resistance.
Project Details
To develop new treatment for infectious disease, we need a nano-scale understanding of complex drug targets in their native state. Very recently, it has become possible to obtain this crucial information due to a revolution in structural biology brought about by breakthrough developments in cryo-EM.
The malaria parasite’s proteasome show potential as a target for the treatment of malaria. Peptide boronate proteasome inhibitors under investigation in the Tilley lab show promise as inhibitors of P. falciparum and specific asparagine ethylenediamine have been reported recently.
The proteasome is like a shredder that chews up damaged or used-up proteins. Treating malaria parasites with proteasome inhibitors leads to the accumulation of damaged proteins and causes cell death. The Tilley/ Hanssen groups have already solved the structure of the plasmodium proteasome and now plan to use the method to facilitate drug design.
