Abstract:
Dr Ghosh’s group employed synthetic peptide models to understand structure-function relationships in various proteins and peptides that include pore-forming toxin,
hemolysin-E, naturally-occurring antimicrobial peptides (AMPs), voltage-gated K+-channel, KvAP, innate immune proteins, MD2 & TLR4
and glucose-regulating protein-hormone, adiponectin and designed biologically-active peptides from these molecules. The long-term
goal of his group is to design peptides/peptidomimetics of pharmacological importance. His group identified leucine zipper like
sequences in AMPs for the first time and demonstrated their crucial roles in cytotoxic and anti-endotoxin activities. His group
demonstrated the design of novel cell-selective AMPs with anti-endotoxin and/or anti-cancer properties by employing heptad repeats
of leucine/phenylalanine and converted a short aβ-stretch into an anti-endotoxin peptide with in-vivo activity and nano-structure.
They identified for the first time a TLR4-derived peptide with self-assembling and pro-inflammatory properties and which showed
significant efficacy as an adjuvant with activation of cellular responses in mice. Further, they identified a unique 13-residue
stretch from the collagen domain of adiponectin which induced AMPK-activation in APPL1-dependent pathway, stimulated glucose
uptake in the rat skeletal muscle cells and significantly decreased blood-glucose in db/db mice.
A brief description of research activities in Dr. Ghosh’s Lab:
Structure-function studies of proteins and peptides and design of bioactive peptides:
There is an urgent need for the design and identification of novel antibiotics due to the emergence of bacterial strains, resistant to conventional drugs. Moreover,
not only live bacteria but dead bacteria could also pose serious threat to host. Stimulation of host defense by bacterial remains such as lipopolysaccharide
(LPS)/lipoteichoic acid (LTA) from dead or live bacteria establishes a local inflammation which when spreads through the circulatory system to an uncontrolled
state develops into sepsis. Sepsis is often associated with multi-organ failure resulting in death of patients. Despite huge efforts, a proper treatment of sepsis
is yet to be made available to the patients, making it an important area of research for drug development. Among the various options available to deal with bacterial
growth and its toxic debris together, antimicrobial peptides (AMPs) emerge as promising candidates with therapeutic potential since many of these peptides can
inhibit both bacterial growth and neutralize the toxic effect of bacterial cell debris. A large number of antimicrobial peptides, which exhibit broad-spectrum
activity against microorganisms including Gram-positive and Gram–negative bacteria with their resistant versions, fungi, protozoa, viruses, and even tumors, have
been identified from a wide variety of animals as well as humans. One of the advantages of AMPs is that majority of these peptides cause damage to the microbial
cell membrane and thereby destroys their cellular integrity within a short time and therefore it is believed that the bacterial resistance will not be developed
easily against these peptides.
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