Chemical Biology Research in India

Chemical biology, as the terminology suggests, is the intertwining of chemistry and biology. However, the exact definition of chemical biology has been constantly debated among the researchers working at the interface of chemistry and biology. One of the major differences between the closely related fields of biochemistry and chemical biology is that the former is more relevant to the actual physiological scenario, whereas the latter has a synthetic feel to it. Thus, exploring biology with the aid of chemical tools can be considered to be the main philosophy of chemical biology. The science of chemical biology in the present form is only about 2 decades old, and hence the successes and failures in this area are more in the limelight than many other fields of science. All over the world, there are active initiatives to merge this new area of research into the scientific mainstream. Universities such as MIT, Harvard, RIKEN, and McGill have full-fledged departments dedicated to chemical biology. Perhaps the earliest research institute in the world dedicated to chemical biology was the CSIR-Indian Institute of Chemical Biology in Kolkata, India. The 75-year-old research institute was reoriented and renamed in 1982 to its present form to explore the chemistry of life—with chemical and biochemical tools. In India, this exciting area of research has spread beyond this institute, and in this In Focus article we shall highlight the status of chemical biology research in India with respect to its past, present, and future. Although work at the interface of chemistry and biology is widespread in India, we will largely focus on institutions that use chemical tools to explore biology

J. Neurosci.

Although the brain functions of specific acetyltransferases such as the CREB-binding protein (CBP) and p300 have been well documented using mutant transgenic mice models, studies based on their direct pharmacological activation are still missing due to the lack of cell-permeable activators. Here we present a small-molecule (TTK21) activator of the histone acetyltransferases CBP/p300, which, when conjugated to glucose-based carbon nanosphere (CSP), passed the blood-brain barrier, induced no toxicity, and reached different parts of the brain. After intraperitoneal administration in mice, CSP-TTK21 significantly acetylated histones in the hippocampus and frontal cortex. Remarkably, CSP-TTK21 treatment promoted the formation of long and highly branched doublecortin-positive neurons in the subgranular zone of the dentate gyrus and reduced BrdU incorporation, suggesting that CBP/p300 activation favors maturation and differentiation of adult neuronal progenitors. In addition, mRNA levels of the neuroD1 differentiation marker and BDNF, a neurotrophin required for the terminal differentiation of newly generated neurons, were both increased in the hippocampus concomitantly with an enrichment of acetylated-histone on their proximal promoter. Finally, we found that CBP/p300 activation during a spatial training, while not improving retention of a recent memory, resulted in a significant extension of memory duration. This report is the first evidence for CBP/p300-mediated histone acetylation in the brain by an activator molecule, which has beneficial implications for the brain functions of adult neurogenesis and long-term memory. We propose that direct stimulation of acetyltransferase function could be useful in terms of therapeutic options for brain diseases