ANNUAL REPORT - Department of Biotechnology

cytokine-mediated regulation of intracellular
trafficking demonstrates that cytokine differentially
regulates endocytic trafficking by controlling the
expression of appropriate Rab GTPase. Several
protease-trans-peptidase enzymes (sortases) from
Staphylococcus aureus and S. pneumonia, were
expressed to study their structure, mechanism of
action and inhibition with a view to develop
therapeutic inhibitors.
Studies on biotin biosynthesis pathway, which does
not exist in humans, suggests that it can be an
attractive target for the development of novel drugs
against a number of pathogens. Studies on the
characterization of the enzyme 7-keto-8aminopelargonic
acid (KAPA) synthase showed
broad substrate stereo-specificity in M. tuberculosis
KAPA synthase. It sets the stage for inhibitor design.
Another study provides a new possibility that iron
can potentate protozoan parasite (Leishmania)
death induced by metalloids like arsenic and
antimony. Continuing studies on M. tuberculosis
have resulted in identification of a new gene cluster
which is required for iron acquisition. Since iron
plays a key role in the development of infectious
diseases, the biosynthetic pathways that have been
studied with the functioning of gene cluster,
represent an attractive target for developing an antibacterial.
M. tuberculosis require mycobactins
(membrane associated siderophores) for acquiring
intracellular iron so as to adapt to it's intracellular
habitat.
2+
During low iron conditions, the IdeR-Fe complex is
not formed, which results in the activation of
transcription of IdeR-repressed genes. The iron box
Iron transport system operating in
M. tuberculosis during low iron conditions
DBT Annual Report 2006-07
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promoters (Fe-box) are found adjacent to both mbt-1
and mbt-2 clusters whereas mbt-1 gene cluster
produces mycobactin skeleton and mbt-2 cluster
produces acyl-S-ACP intermediates.
These acyl-S intermediates are then transferred to
produce didehydroxymycobactin in the presence of
MbtK. The final hydroxylation is carried out by MbtG
to generate the amphiphilic mycobactin
siderophore).
Genetics, Cellular Signalling & Cancer Biology
Study has revealed a novel signaling pathway
involving PfPKB, a protein kinase B-like enzyme from
Plasmodium falciparum wherein calcium/calmodulin
works as the upstream activator suggesting probable
intercepting pathways. Studies related to SPAG9
expression and immuno-genicity in epithelial ovary
cancer patients (EOC) shows that majority of
epithelial ovary cancer tissues exhibited SPAG9
expression at both mRNA and protein level. The
study further indicates that SPAG9 is highly
expressed in EOC and is immunogenic in patients.
Work on BLM helicase in the Bloom Syndrome (BS)
patients who are predisposed to almost all types of
cancers has indicated that it may act in two different
stages of the transmission of DNA damage signal
during replication. It is thus possible such proteins
can have physiological functions different than that
are presently ascribed to them. Studies on the
genomics of human Y chromosome in patients with
sex chromosome related anomalies (SCRA) and
males exposed to natural background radiations
(NBR) revealed AZFc somatic micro-deletions and
copy number polymorphism of the DAZ genes.
Reproduction & Development
Studies on understanding the molecular basis of
fertilization in humans have demonstrated that Cterminal
fragment of human ZP3- the primary sperm
receptor, is able to induce acrosomal exocytosis in
capacitated human spermatozoa. Deletionrecombinant
fragments made and being investigated
for sperm receptor activity are expected to help in
developing drugable novel contraceptive molecules.
Multiplex PCR has been designed and validated to
screen Y chromosome micro-deletions in infertile