Amogh Anant Sahasrabuddhe, Ph.D.
Principal Scientist, Molecular and Structural Biology
We study the protozoan parasite Leishmania that affects millions of poor people across the world with three major forms of diseases namely cutaneous,
mucocutaneous and visceral leishmaniasis. Out of these, visceral leishmaniasis (VL) is the most fatal form and is prevalent in the Indian subcontinent.
Current treatment regimen for VL suffers with high toxicity, drug resistance and high cost. There are no vaccines available to control the spread of this
disease.
Leishmania cells exist in two morphologically distinct forms, the insect form (promastigotes) is spindle shaped, flagellated and highly motile whereas the
intramacrophage form (amastigote) is oval, non-motile and contains a non-emerging rudimentary flagellum. This change in shape during the infection cycle
is governed by its cytoskeleton. We are inclined to decipher role of actin cytoskeleton proteins and their importance in the shape transformation of
Leishmania parasites. Our approach to study protein function is by creating gene knockout/knockdown mutants, over-expressing native as well as functionally
mutated proteins in Leishmania and by biochemical analysis of purified proteins.
Leishmania infection generates Th1 type of immune response and creates lifelong protection against re-infections. Once cured, the patient becomes immune to this
disease. This information is useful to consider Leishmania proteins as potential vaccine candidates. Our lab is involved in identifying Th1 stimulatory
proteins and to develop vaccine for Indian VL.
Leishmania as such are relatively less understood parasites in terms of their own physiology and infection biology. From ~8000 genes identified through genome
sequencing, only ~36% of genes have yet been annotated for function. Clearly, a large number of Leishmania genes possess novelty and potential drug
targets and vaccine candidates are still in the folds. The genetic analysis of large number of genes requires appropriate molecular tools and quicker
methods. The available methods like knocking out gene of interest and creating dominant negative mutants are labor intensive, time consuming and suffer
high failure rate. Our research interests encompass development of novel methods and technologies for quicker genetic analysis of large number of genes
in Leishmania and identification of biomarkers of diagnostic importance.
View More..