Chemical & Systems Biology
Chemical approaches are essential in the understanding of many biological phenomena. Several research groups at IGIB have come together to utilize their varied expertise in different disciplines of chemistry and biology to address contemporary research problems that require interdisciplinary cross-talk. Research carried out at IGIB in this area involves:
* Chemical biology and systems biology of M. tuberculosis and skin pigmentation
* Chemically modified oligonucleotides for biological applications
* Novel immunoassay procedures
* New molecules: Linkers for biochip development| Peptide scaffolds and peptidomimetics| Quadruplex –stabilizing ligands
Chemical and Systems Biology of M. tuberculosis and skin pigmentation
Understanding the mechanism by which the pathogenic microorganism M. tuberculosis modulates the expression of the proteins and lipids present on its cell wall is one of the focus areas of research at IGIB. In particular, the role of polyketide synthases in lipid biosynthesis is being dissected using a combination of biochemical, genetic and systems approaches.
Research is also being carried out to understand the molecular events that lead to pigmentation in human skin. Of particular interest is developing a comprehensive understanding of the biochemical mechanisms underlying the melanin and melanocyte disappearance in vitiligo.
Chemical modulators of bio-activity
Chemically modified oligonucleotides like the Locked Nucleic Acid (LNA) with enhanced specificity and stability are better suited for therapeutic applications. Research at IGIB is directed towards investigating hybridization thermodynamics of modified oligonucleotides in order to understand their stability and formulate guidelines for the optimum design of LNA based oligonucleotides. These are specifically being used to stabilize or perturb quadruplex and i-motif forming DNA sequences. Ligand-induced stabilization of unusual DNA structures to aid development of anticancer agents is also being explored.
Designing and synthesis of biologically active, antihypertensive peptidomimics (ACE inhibitors) and novel chimeric opioid peptides with improved bioavailability and pharmacokinetic profiles is an important area in drug development research at IGIB.
Nanoparticle-mediated DNA delivery & nano-toxicity
Several research groups in IGIB are involved in synthesis as well as in vitro and in vivo activity studies of novel, efficient and non-toxic nano-delivery systems based on cationic polymers and peptides. The structure of the cationic surfactants in controlling DNA condensation is also being studied using a wide range of biophysical techniques. In addition, mechanistic study on packaging processes of different DNA nanocarriers based on polymers and peptides using Atomic Force Microscopy and correlating their intracellular delivery efficiency with packaging is also being carried out. These approaches are likely to lead to design of new materials for targeted delivery. A toxicogenomic approach is being applied to observe and rationalize the toxicity effects of gold, silica and other nanoparticles in both cultured cells as well as in a zebrafish model system.
IGIB has been involved in developing different modifed ELISA procedures using heat, sunlight, pressure etc. to adapt ELISA for clinical applications by cutting down on the turn around time. Some of these methods have been used for rapid and sensitive detection of autoantibody in rheumatoid arthritis patients and cell adhesion molecules in HUVEC cells. Development of bio-sensors for detection of microbial pathogens and metabolites is another area of interest at IGIB.
Efficient protocols for covalent immobilization of biomolecules on inorganic and organic surfaces have been developed at IGIB towards developent of bio-chips. This has involved improvisations in the attachment chemistry of oligonucleotides on different surfaces (modified glass, polypropylene, polystyrene etc.) and development of novel heterobifunctional reagents for surface immobilization of biomolecules on solid surface. Designing modified oligonucleotides with suitable functionality for immobilization on bio-chips is also being carried out.