|
|
 |
BIOGRAPHY:
Dr. Soldati earned her Ph.D. in the field of molecular biology from the University of Zürich in 1990. From 1991 until 1995 she conducted postdoctoral research in the Department of Microbiology and Immunology of the Stanford University School of Medicine in the United States. In 1994 she received a Research Award from the Swiss Society of Microbiology for her work in the development of transfection in Toxoplasma gondii. Dr. Soldati conducts research at the University of Geneva, working on a project entitled "Study of Membrane-Bound Serine and Aspartyl Proteases in
Toxoplasma gondii."
RESEARCH ABSTRACT SUMMARY:
Study of Membrane-Bound Serine and Aspartyl Proteases in
Toxoplasma gondii
The apicomplexan parasites have adopted an intracellular lifestyle
that allows them to successfully evade the host defense mechanisms. The
survival strategy of Toxoplasma gondii in particular is to
infect virtually all nucleated cells in its many vertebrate hosts,
utilizing a distinct form of actomyosin-dependent gliding motility to
propel itself into host cells. Gliding motility is driven by the
discharge of adhesive complexes at the apical pole of the parasite and
by their redistribution toward the posterior pole of the parasite.
During invasion, the transmembrane proteins are rapidly released from
the parasite surface by the action of a protease called MMP1, which is
affected by 3,4-dichloroisocoumarin (DCI), a serine protease inhibitor
previously shown to block invasion. The intramembrane cleavage site of
MPP1 is preserved in a range of apicomplexan proteins, suggesting that
the protease is present and conserved across the phylum. The rhomboids
are polytopic membrane proteins forming a new family of
intramembrane-cleaving serine proteases, and several genes encoding
rhomboid-like proteins are present in the apicomplexan genomes,
constituting plausible candidates for MPP1 activity. Members of this
family are currently being characterized in order to assess their
substrate specificity and their biological role in T.
gondii.
The asparyl proteases constitute an important class of enzymes that
have been recognized as appropriate and effective targets for
chemotherapy against several infectious diseases, including malaria. In
Plasmodium, these Plasmepsins, as these proteases are called,
are targeted to the digestive vacuole and involved in hemoglobin
degradation. At least one highly conserved protease related to
Plasmepsin VI is also found in several other apicomplexans. In
Eimeria tenella, Eimepsin is present within the apical tips of
invading sporozoites, but its function during invasion is still
unknown. In T. gondii, two Toxomepsins are currently under
investigation to determine their subcellular distribution, maturation
process, and possible function.
Photo: Kent Kallberg, Kallberg Studios
|
