Science, Technology and Engineering

Foley Laboratory

Department of Biochemistry

Research - Anti-Malarial Therapeutics

The main goal of our group is to understand, at the molecular level, the biology of infectious diseases including malaria and anthrax and to use this information to aid the development of new diagnostic and therapeutic approaches to these diseases.

The use of specific binding peptides from random peptide libraries, and phage display of protein domains, combined with monoclonal antibodies and other molecular approaches helps advance our understanding of the structure and function of proteins and work out their in the life cycle of the pathogen. Furthermore, we are exploring the uses of the peptide reagents in designing and improving diagnostic tests for detecting the infectious agent. Using the peptide as lead compounds for new and improved therapeutic strategies is also a priority for our lab.

As part of our work with the Cooperative Research Centre for Diagnostics (CDx), we have constructed a random peptide library of up to a thousand million different 20-mer sequences. This library has been used to identify binders to many infectious diseases targets and other systems. Currently we have several areas of interest:

MALARIA (click for more details)

Malaria remains one the most lethal infectious diseases particularly with the recent increase in forms of the parasite resistant to many of the best anti-malarial drugs and still no vaccine. Plasmodium falciparum malaria parasites (merozoites) bind to and invade human red blood cells, where they grow without being destroyed by the host immune system. Molecules on the parasite surface are thought to be involved in the invasion process.

Current work in our laboratory is involved in the search for a molecular vaccine and exploring the function of malarial antigens to gain a deeper understanding of the host parasite interaction. From our random 20-mer peptide library, we have:

• Peptides that bind to malaria antigens and inhibit red blood cell invasion

• Mapped the inhibitory epitope space on AMA1 and other malaria antigens

• Peptides that mimic epitopes on malaria and EBV antigens

Structures of AMA1 binding peptides and peptide mimics of AMA1:

In collaboration with Dr Ray Norton (WEHI), we are exploring the structure of these peptides in order to determine the features required for biological function.

In collaboration with Dr Tim Haystead's group (Duke University, North Carolina, USA) we have used the approach of proteome mining to identify potential drug target in the malaria infected red blood cell.

ANTHRAX (click for more details)

From our library we have isolated a peptide that binds to the active site of Lethal Factor (LF), the protease component of anthrax toxin. This peptide is being developed as a potential drug lead for anthrax.