ANNUAL REPORT - Department of Biotechnology

factors. Scientists at Sree Chitra Tirunal Institute for
Medical Sciences and Technology, Trivandrum used
an in vitro cell culture model to evaluate the response
of adult rat cardiac fibroblasts to hypoxia.
Uracil DNA glycosylases (UDGs) excise uracil from
DNA and initiate the base excision repair pathway. Of
the known UDGs, Ung proteins belong to a category
of highly conserved and efficient enzymes, and
shown to be crucial in mycobacteria. Studies carried
out at IISc Bangalore revealed that UdgB plays a
significant role in mycobacteria.
The ability of MTB to survive and adapt to changing
environmental conditions appear to be regulated
largely by two-component signaling systems (TCS).
Of the eleven TCSs that MTB possesses, the PhoP-
PhoR system is the only one disruption of which has
been shown to drastically affect the bacillus's
replication in cellular and animal models. Scientists
at IMTECH., Chandigarh have shown that phoP
promoter activity is negatively autoregulated by
PhoP through sequence-specific interaction(s)
involving 3 direct repeat subunits with a 9-bp
consensus binding sequence.
One of the most clinically significant mechanisms of
azoles resistance in the pathogenic fungi, Candida
albicans is an over expression of the drug efflux
pumps encoding genes CDR1 and CDR2 belonging
to the ABC (ATP-Binding Cassette) and CaMDR1
belonging to MFS (Major Facilitator Superfamily)
transporters. Among the ABC transporters, high level
of expression of CDR1 invariably contributes to an
increased efflux of fluconazole and thus
corroborates its direct involvement in drug efflux.
The study conducted at JNU, New Delhi suggests
that Asp327 of N-terminal NBD has acquired a new
role to act as a catalytic base in ATP hydrolysis, a role
normally conserved for Glu present adjacent to the
conserved Asp in the Walker B motif of all the nonfungal
transporters.
Proteomics
Many proteins in Escherichia coli are initially
synthesized in their precursor form with a signalling
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motif, the signal peptide that directs them to their
target membrane. SecB is a soluble cytosolic
chaperone component of the sec export pathway
which binds to the newly synthesized precursor
proteins thus preventing their premature aggregation
and folding and then targets them to the translocation
machinery on the membrane. PreMBP is the
precursor form of maltose binding protein (MBP) with
a 26-residue signal sequence. Studies carried out at
IISc, Bangalore indicates that both MBP and preMBP
are more prone to aggregation under crowded
conditions with preMBP showing a greater extent of
aggregation.
The tumor suppressor protein p53 regulates
transcription of many genes, which mediate cell
cycle arrest, apoptosis, DNA repair and other cellular
responses. Studies being done at CCMB,
Hyderabad has shown that caspase-1 activator Ipaf
is a p53-inducible gene involved in apoptosis
because blocking of Ipaf function by RNA
interference or by a dominant negative mutant
reduced p53-induced apoptosis. To determine the
molecular components involved in p53-dependent
apoptotic pathway, they have analysed the role of
Ipaf and caspase-1. Since the mechanism by which
caspase-1 executes apoptosis under these
conditions is not known, the investigators have also
determined the sequence of events that lead to
apoptosis upon caspase-1 activation by Ipaf. The
results show that Ipaf is involved in p53-dependent
apoptosis (induced by PTP-S2) and that caspase-1
activated by Ipaf primarily functions upstream of
mitochondrial events to mediate p53-dependent
apoptosis.
SMARCAL1 belong to the SWI/SNF family of DNAdependent
ATPases. The SWI/SNF protein family
has been shown to be involved in all DNA metabolic
processes- DNA replication, DNA repair,
transcription, and DNA recombination. Scientists at
School of Life Sciences, JNU carried out
experiments to delineate methods to explore the
physiological role of SMARCAL1. The conditions for
over-expression and solubilization of the protein
have been standardized.