Alan Cowman

THE 2006 LEMBERG MEDAL: ALAN COWMAN

Alan CowmanAlan Cowman is located at the Walter and Eliza Hall Institute of Medical Research (WEHI). Originally from Brisbane, he completed his BSc (Honours) at Griffith University in 1979 and then moved to Melbourne where he completed his PhD degree, under the supervision of David Kemp, at WEHI in 1984. This was followed by a postdoctoral position for two years, supported by a CJ Martin Fellowship, with Gerry Rubin, then at the University of California, Berkeley. After returning to the WEHI at the end of 1986, he continued to work with David Kemp and was awarded a Wellcome Trust Australian Senior Research Fellowship in 1988, followed by the first of three International Research Scholarships from the Howard Hughes Medical Institute. In 1999 he was appointed Head of the Division of Infection and Immunity, and was awarded the ASBMB Boehringer-Mannheim Medal in 1994.

Alan’s main interests have revolved around protozoan parasites, in particular Plasmodium falciparum, the causative agent of the most lethal form of malaria. He has made major contributions to understanding drug resistance, elucidating the mechanism of resistance to some of the most important antimalarial drugs. This has not only had important implications for the development of new antimalarials but also opened the way for surveillance of the spread of drug resistance alleles.

Alan is particularly interested in how the malaria parasite invades human erythrocytes and subsequently remodels the host cell, harvesting the required nutrients for its growth and development while escaping the immune responses deployed against it. This has resulted in work to understand antigenic variation through switching expression of variant surface proteins encoded by the var gene family, suggesting that var locus repositioning and heterochromatic silencing play important roles in the epigenetic regulation of virulence genes. These virulence proteins are expressed on the parasiteinfected erythrocyte surface in structures known as knobs. In the first gene knockout in P. falciparum, he and his colleagues showed that the knob associated histidine-rich protein (KAHRP) was essential for formation of these structures and that they are required for cell adhesion under physiologically relevant flow conditions, an important component of the pathogenesis of this parasite. Analysis of proteins exported into the Plasmodia-infected erythrocyte identified a novel shared motif; this work also showed that up to 10% of the genome of this parasite encodes proteins that are exported into the host erythrocyte. This enabled identification of proteins responsible for remodelling of the host erythrocyte, providing new insights into a process essential for the virulence and pathogenesis of this parasite.