Chemical Biology and Molecular Medicine at IISc, Bangalore
Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide play crucial roles in redox biology and cell signaling. Excessive amounts of ROS induce oxidative stress, resulting in damage to biomolecules such as DNA, proteins, and lipids. In the long term, these damages lead to various disorders, such as neurodegeneration, HIV activation, cardiovascular diseases, cancer, and aging. Mugesh’s group developed the concept of synthetic enzymes as redox modulators and mediators of cellular redox signaling. His group worked extensively on the rational design and synthesis of novel small-molecules and nanomaterials that can control the redox state of the cells by functionally mimicking the enzyme glutathione peroxidase (GPx). The unique properties of these molecules make them suitable for the development of therapeutic candidates to tackle diseases associated with oxidative stress. Mugesh’s group has also contributed significantly to the understanding of the molecular mechanism of thyroid hormone action. His group has carried out extensive work on the selective removal of iodine from thyroid hormones, and established how such selectivity of a fundamental chemical process controls the thyroid hormone homeostasis in human body.
Heart failure is a major public health problem that affects human population throughout the world. Although our understanding of the of the mechanisms causing heart failure has improved over the decades, still we are unable to effectively treat cardiovascular diseases. In the failing human heart, several abnormalities have been recognized, which includes defects in the key signal transduction pathways, the transcription and translational machinery. However, the molecular events leading to initiation of heart failure is not yet fully understood. Ravi's laboratory is trying to understand the mechanisms of heart failure using novel cell culture based techniques and animal models. His laboratory is currently focused on two molecules – (1) Sirtuins, a family of Class III histone deacetylases, and (2) Poly (ADP-Ribose) polymerases. They are trying to identify their role in the cardiovascular and muscle biology especially in diseases such as cardiac hypertrophy, fibrosis, and muscle degeneration. Their goal is to uncover biological functions of these enzymes that can be therapeutically targeted for promoting the health span of humans.
Debasis explored the mechanism and structure of a challenging integral membrane metallo-enzyme, phosphoglycosyl transferase, in the N-linked protein glycosylation pathway of the pathogenic bacteria Campylobacter jejuni. The enzyme serves as a potential therapeutic target for C. Jejuni infection. The new insight derived from the mechanism and the structure of this enzyme has fuelled small molecule inhibitor development targeted towards attenuation of the virulence of C. jejuni as well as a wide range other microbial pathogens that employ homologous enzymes. Debasis’s current group is working at the interface of Chemistry and Biology. The research activities are focused on mechanistic understanding of various metallo-enzymes and their applications. Employing various tools of chemistry, biochemistry and molecular biology Debasis’s group is exploring function, kinetics, mechanism and reaction intermediates of several poorly understood enzymes. The group is also very keen to engineer and utilize these enzymes in green energy applications and therapeutics.
Organoboron compounds play a pivotal role in organic synthesis, being utilized as essential precursors in the realm of C–C, C–O and C–N bond formation via the cross-coupling reactions. In addition to their unique applications in organic synthesis, boronic acids also have gained increasing significance in medicinal chemistry and chemical biology. Of particular importance, boronic acids have been developed as potential therapeutic agents, chemical biology tools, and drug delivery vehicles. Consequently, their direct generation from simple, poor pre-functionalized substrates continually arouses interest of the synthetic community and is actively pursued. Geetha’s research group is mainly focused on the development of cost effective, earth abundant, less toxic base metal catalysts and main group catalysts for the synthesis of organoboranes. Recently, her group developed an efficient cobalt catalyst for the formation of valuable branched alkylboronic esters and aryl boronates. We are also in the processes of developing chalcogen based organo-catalysts and light assisted catalysis for different types of organic transformations.
Primary focus of Sandeep's laboratory is to understand the events that cause translational readthrough in certain mammalian transcripts. They have identified several transcripts that show this phenomenon. They are investigating the mechanism, regulation and physiological significance of this process using mammalian cell culture and mouse models. Many genetic diseases are caused by non-sense mutations that cause a premature stop codon in the protein-coding transcript. Sandeep's group is trying to develop molecules that can induce translational readthrough across these disease-causing premature stop codons. Angiogenesis is another area of their interest. They have recently developed a method to induce angiogenesis using controlled shock waves in collaboration with Prof. Jagadeesh from Aerospace Engineering Department of IISc. They have recently started a new project on Tardigrades, microscopic animals that show incredible resistance to a variety of physical and chemical stresses. They have isolated a new species from a tree in IISc that shows remarkable UV-tolerance. In collaboration with Prof. Mugesh (IPC), they are trying to understand the chemical nature of the compound that confers UV-tolerance to these newly identified tardigrades.
Research in Biju's group involves the strategies for reaction methodology development to stand on contemporary problems in reaction discovery, and targeted synthesis. In this context, they believe that transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions are key and green technologies, which is anticipated to become more and more important in the future. The main research areas of Biju's group are: Aryne Chemistry, Asymmetric catalysis, Donor-Acceptor Cyclopropanes and N-Heterocyclic carbene organocatalysis. Their present research focuses on the development of transition-metal-free carbon-carbon and carbon-heteroatom bond-forming reactions, and their implementation in organic synthesis. Specifically, they employ aryne chemistry for the rapid synthesis of various 1,2-disubstituted arenes. They also use N-heterocyclic carbene (NHC) based organocatalysis for the enantioselective construction of heterocycles and carbocycles. In addition to the synthesis of the benzo-fused compounds and chiral heterocycles, evaluation of the biological activity of these molecules forms part of their research.
The central theme of our interdisciplinary BioNanoChemistry group is an emerging area of nanobiotechnology: the role of surface chemistry on nanomaterials in modulating the materials-biology interface. This aspect is particularly crucial for biological applications of nanomaterials given the central role of surface chemistry in constructing biomaterials with appropriate functionalities and biocompatibilities. Rana's group has demonstrated the utility of these novel materials in different bio-applications including diagnostics, drug discovery and therapeutic delivery. Currently they are developing smart strategies for preparing self-assembled materials with chemical functionalities. Structure-activity relationships enable them learning about the molecular interactions that interface materials and biology. Long-term, they aim to innovate effective point-of-care diagnostics for different diseases with personalized screening abilities, novel platforms for precision medicine, and tissue engineering incorporating the desired materials properties.