ANNUAL REPORT - Department of Biotechnology

functionality of ORP150 - a novel ER chaperon.
Infection & Immunity
Towards further understanding the biology of
Leishmania, the selenophosphate synthetase [selD]
gene has been cloned and characterization of the
role of the protein with respect to its cellular
localization and stage-specific expression in the
parasite is in progress. The studies on the
mechanism of immuno-suppression in leishmaniasis
revealed that in vivo suppression of ERK-1/2 or
exaggeration of p38MAP kinase might result in the
amelioration of Leishmania infection. Further
investigation led to the conclusion that the anti-IL-2
treatment is effective in the early phase of infection
while IL-10 blockade is effective at a later stage of
infection. Taken together, these findings could lead
to the development of prophylactic and therapeutic
principles for the dreaded disease.
The modulation and induction of CTL responses, by
different antigen presenting cells can provide key
information in studies of CD8+ T cell mediated
immunity. NCCS has been successful in the
isolation and characterization of dendritic cell types 1
and 2 (DC1 & DC2). Further, activation of these
through the T-independent and T-dependent modes
revealed that the DC1 cells have a stimulatory effect
while the DC2 cells are regulatory in nature.
Genome sequencing of poxviruses and
herpesviruses has shown that members of these
families encode structural homologs of human
regulators of the complement activation (vCCP) to
mask themselves against the host's complement
attack. Thus, the Herpesvirus saimiri homolog (HVS
CCPH) was seen to possess all the complement
regulatory activities present in kaposica and VCP,
and exhibits 14-fold higher factor I cofactor activity
against C3b. Site-directed mutagenesis revealed
that R118 contributes significantly to the factor I
cofactor activity of HVS CCPH.
The study on HIV biology led to the elucidation of
Hsp40 as a crucial player in Nef-mediated
enhancement of HIV gene expression and
replication. Anisotropy studies using fluorescein
labeled DNA suggested that Tat binds to NFB
enhancer DNA as a dimer with binding affinity in
nanomolar range. Further, the Tat:NFκB interaction
followed a two site sequential binding model and
could be responsible for Tat mediated modulation of
cellular genes. Preliminary evidence also indicated
the importance of IFN-γ in inducing expression of
CTL effector molecules perforin and granzyme,
emphasizing that the rescue of impaired CTL
functions might help devise an immunotherapeutic
strategy to control HIV replication or boost existing
strategies.
Chromatin Architecture & Gene Regulation
Understanding the role of a MAR binding protein,
SMAR1, in many cellular processes has been
another area of interest. This tumor suppressor
activates p53 through phosphorylation that in turn
modulates global transcription from various
promoters. PGA2 mediated repression of Cyclin D1
transcription and cell cycle arrest requires SMAR1.
SMAR1 also inhibits TGFβ signaling and its
downstream target genes that are involved in tumor
cell migration and metastases. In another study,
phosphorylation of the T-cell specific transcription
factor SATB1 was seen to determine its association
with either HDAC1 or PCAF. Further, it has been
found that recruitment of the chromatin modifiers
HDAC1 or PCAF to the IL-2 promoter in vivo is
dependent on the phosphorylation status of SATB1
at serine 185. It has been observed that
phosphorylation and acetylation of SATB1 have
contrasting effects on gene expression at a global
level. Collectively, these studies have significantly
advanced our knowledge about the mechanisms of
global gene regulation.
Biodiversity
Understanding the microbial community structure of
unique ecosystems like insect gut, human colon and
some extreme ecosystems is another area of
research at NCCS. In the case with Aeromonas
culicicola, a microbe from the midgut of mosquito, the
distribution of its toxin genes that are implicated in its
virulence was used to assess the extent of
pathogenicity in these organisms. The study
described for the first time the presence of
Ochrobacterium intermedium in the antrum of a nonulcer
dyspeptic patient diagnosed with H. pylori, in a
view to asses the correlation of infection by these
181 Autonomous Institutions