Malcolm McConville
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Molecular microbiology
Protozoa and
mycobacteria cause a number of human diseases, including malaria and
tuberculosis, that collectively affect more than a quarter of the world's population.
These microbial pathogens are all coated with specialized molecules that
allow them to invade particular tissues or cell types and evade the host
immune system.
The specialised cell surface molecules have a number of different functions. They may form protective cell walls or surface
coats, mediate specific hostpathogen recognition and attachment events, and also modulate
the host immune system.
Leishmania parasites expressing a green fluorescent marker for organelles involved in the synthesis of major surface glycolipids
The goals of our research are:
- to define the structure and function of the microbial cell surface molecules
- to understand how microbial cell surface molecules are synthesized and transported to their sites on the surface of the pathogen
Our studies employ a broad range of techniques, including:
- the in vitro cultivation of protozoan and bacterial pathogens;
- the isolation and chemical characterization of cell surface molecules (primarily glycoproteins, proteoglycans and glycolipids) by mass spectrometry, HPLC and other chromatographic methods;
- the reconstitution of biosynthetic pathways in both living cells and cellfree preparations;
- the purification of specific enzymes and/ or cloning of relevant genes; and
- analysis of the subcellular organization and enzymology of these biosynthetic pathways.
The surface biochemistry of protozoan parasites
Parasitic protozoa are the causative agents of several widespread diseases
in humans, including malaria (Plasmodium falciparium), the leishmaniases (Leishmania
spp) and amoebic dysentry (Entamoeba histolytica). These parasites all
synthesize a class of glycolipids, termed glycosylphosphatidylinositols (GPIs) that anchor
the major surface proteins to the plasma membrane and are also important membrane
components in their own right.
In addition to being essential cell surface components,
GPIs may also directly modulate the immune response of the host. Given these
important roles for GPIs in the biology of protozoa, enzymes involved in their biosynthesis are potentially attractive targets for new,
urgently needed, antiparasite drugs.
Our current research is directed at:
- delineating pathways of GPI biosynthesis in these parasites;
- cloning genes involved in GPI biosynthesis;
- defining the routes of intracellular trafficking of GPI glycolipids; and
- characterizing novel subcellular organelles involved in lipid biosynthesis.
Biosynthesis of the mycobacterial cell wall
Worldwide, tuberculosis is the foremost cause of death by a single infectious agent. The causative agents, mycobacteria, are encapsulated in a complex cell
wall that protects them from the host's immune system and most antibiotics.
We have
a joint program with a group from the Department of Microbiology at Monash University to
investigate the biosynthesis of different mycobacterial cell wall components. We have
a panel of transposon cell wall mutants and methods for
identifying the mutated gene and investigating the function of the encoded protein in cell
wall biosynthesis.
These studies have already led to the identification of several genes
and enzymes that are likely to be essential for mycobacterial virulence. They will continue to provide new insights into the biogenesis of these complex wall structures.
Lab personnel
Head
Professor Malcolm McConville
Research staff
Dr Julie Ralton (Post-doctoral fellow)
Dr Thomas Naderer (Post-doctoral fellow)
Dr Fleur Sernee (Post-doctoral fellow)
Dr Jim MacRae (Post-doctoral fellow)
Dr Eleanor Saunders (Post-doctoral fellow)
Dr Yoshiki Yoamaryo (Coppel) (Post-doctoral fellow)
Jenny Muth (Research assistant)
Graduate students
Dave de Souza
Jo Heng
William Ng