Hughes grants flow to local malaria researchers

The latest list of international research grants from the Howard Hughes Medical Institute (HHMI) has confirmed Australia's status as a leading nation in malaria research.

Eight Melbourne researchers -- six at the Walter and Eliza Hall Medical Research Institute, and two University of Melbourne researchers -- have secured five-year research grants ranging between AUD$466,000 and $666,000, equivalent to 20 per cent of this year's funding from the HHMI awards scheme.

Only one researcher, University of Melbourne geneticist Prof Alex Andrianopoulos, is not directly involved in malaria research. Andrianopoulos received a $500,000 grant to study Penicillium marneffei, a pathogenic mould that causes lethal infections in AIDS patients, especially in developing nations, and in immunosupressed individuals such as bone-marrow transplant and cancer patients.

Prof Geoff McFadden, of the University of Melbourne's School of Botany, won a HHMI grant to continue his research into the function of a relict chloroplast that he discovered in the malaria parasites and its relatives in the phylum Apicomplexa in the late 1990s.

McFadden's discovery of the organelle, dubbed an apicoplast, proved that the malaria parasite descended from a single-celled photosynthetic alga, related to dinoflagellates, and raised the possibility that drugs targeting the shikimate fatty acid-synthesis pathway, exclusive to plants, might be effective against malaria and other Apicomplexa parasites.

It has been a golden seven days for Prof Alan Cowman, head of infection and immunity at WEHI. Cowman's grant from HHMI comes on top of an announcement last week that his research team will share a US$21 million grant for malaria research, under the Bill and Melinda Gates Foundation's Grand Challenges initiative.

The WEHI team is a member of an international consortium that will share the huge grant to help develop a malaria vaccine. The other members are the Seattle Biomedical Research Institute, and the University of Heidelberg, in Germany. Last week Cowman also received a $12.9 million grant for malaria and leishmaniasis research from Australia's National Health and Medical Research Council.

Cowman's WEHI colleague, Dr Louis Schofield, shared in another $8 million consortium grant from the Gates Foundation -- and backed up this week by winning an HHMI grant for his work on the role of innate immunity and the parasite toxin, in susceptibility and resistance to severe malaria. Individuals who survive malaria in infancy subsequently develop antibody-mediated immunity, and Schofield is attempting to determine whether differences in immunity can be exploited by new therapies.

Other WEHI recipients of HHMI grants are:

• Dr William Heath, who is trying to determine how Plasmodium parasites down-regulate the immune response of their human hosts. Heath and a University of Melbourne colleague, Dr Frank Carbone, are studying the role of dendritic cells, the front-line cells that sense infection. Carbone's work has identified at least two different classes of dendritic cells. One type is located peripherally, in the skin and mucosal surfaces within the body, and appears to transport antigens to a second class of dendritic cells that are stationed at lymph nodes, where they present antigens to visiting T-cells.
• Dr Simon Foote, who now holds a joint appointment as a senior WEHI gene-hunter, and director of the Menzies Research Institute in Hobart, is using mouse models carrying rare mutations that confer protection against malaria to understand how the parasite's hosts animals defend themselves against infection.
• Dr Brendan Crabb will use his HHMI grant to study surface proteins in the parasite's merozoite stage, which are the prime targets for the host immune response, and thus, leading candidates for incorporation in a malaria vaccine.
• Dr Gabrielle Belz's HHMI grant will go towards investigating the processes that induce the host's immune system to produce increased numbers of CD8 memory cells, which are the key to the host developing and maintaining immunity to the parasite.