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BIOGRAPHY:
Dr. Foote received his M.B.B.S. in 1984 and his Ph.D. in 1990 from the University of Melbourne in Australia for his studies on drug resistance in Plasmodium falciparum. He did postdoctoral research at the Whitehead Institute for Biomedical Research in the United States. In 1993 he received a Wellcome Senior Australian Fellowship, and in 1995 was awarded the Burnett Prize. He is currently Principal Research Fellow in the Genetics and Bioinformatics Group at the Walter and Eliza Hall Institute of Medical Research. His HHMI-funded project involves mapping and identifying genes responsible for host response to Leishmania major.
RESEARCH ABSTRACT SUMMARY:
Characterization of Loci Contributing to Host Response to
Leishmania major in the Mouse
We have mapped three loci contributing to the host response to
infection by Leishmania major in the mouse. These loci
(lmr1, -2, and -3) are located on chromosomes 17, 9, and X,
respectively, and control the rate of skin lesion development. We have
generated animals reciprocally congenic for these loci both
individually and collectively. These animals show altered rates of
progression of L. major–induced lesions. There is no
immunological correlate between the phenotype displayed by these
animals and any of the classical cytokines involved in the T helper T
cell response. Microarray analysis of macrophages (the target cell of
the parasite) showed a difference in the expression of genes
controlling wound healing. We have therefore looked more closely at the
lesions and found major differences in the histological structure of
the healing lesion in animals infected with L. major or in
animals given a sterile lesion. In animals in which the lesion healed
rapidly, collagen bundles are well ordered and constitute the major
component of the healing wound. In susceptible animals, there is less
collagen deposition and the pattern of deposition is much less ordered,
almost random. We therefore interpret these findings as evidence that,
in this murine model of L. major susceptibility, the major
determinant of outcome is the ability of the host to heal the
lesion.
Photo: Kent Kallberg, Kallberg Studios
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