INSA: new initiatives and concerns

The Indian National Science Academy (INSA), New Delhi which is currently in its Platinum Jubilee year, has maintained its eminence and dignity all these years. The Fellowship of INSA is highly cherished. The Academy enjoys considerable prestige. This prestige needs to be converted into influence. INSA is in the process of setting up a Science Policy Study Cell. The Academy needs to strengthen its role as a think-tank in the service of the nation on science-related issues. INSA is also in the process of establishing an archive. We can understand the present and plan for the future only in the context of the past. Thirdly, we would like to establish an electronic hub of science information at INSA. We do not wish to solely hold large quantities of information. But we need to have links with all major depositories of science- related information in the country. This is in consonance with the general philosophy of an Academy. The Academy is not a major implementer or executor of policies and programmes. It is a catalyst and a beacon that guides.

targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis

Background: Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results: We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion: The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes.

Sustainable bioenergy for India: Technical, economic and policy analysis

India's energy challenges are multi-pronged. They are manifested through growing demand for modern energy carriers, a fossil fuel dominated energy system facing a severe resource crunch, the need for creating access to quality energy for the large section of deprived population, vulnerable energy security, local and global pollution regimes and the need for sustaining economic development. Renewable energy is considered as one of the most promising alternatives. Recognizing this potential, India has been implementing one of the largest renewable energy programmes in the world. Among the renewable energy technologies. bioenergy has a large diverse portfolio including efficient biomass stoves, biogas, biomass combustion and gasification and process heat and liquid fuels. India has also formulated and implemented a number of innovative policies and programmes to promote bioenergy technologies. However, according to some preliminary studies, the success rate is marginal compared to the potential available. This limited success is a clear indicator of the need for a serious reassessment of the bioenergy programme. Further, a realization of the need for adopting a sustainable energy path to address the above challenges will be the guiding force in this reassessment. In this paper an attempt is made to consider the potential of bioenergy to meet the rural energy needs: (I) biomass combustion and gasification for electricity; (2) biomethanation for cooking energy (gas) and electricity; and (3) efficient wood-burning devices for cooking. The paper focuses on analysing the effectiveness of bioenergy in creating this rural energy access and its sustainability in the long run through assessing: the demand for bioenergy and potential that could be created; technologies, status of commercialization and technology transfer and dissemination in India; economic and environmental performance and impacts: bioenergy policies, regulatory measures and barrier analysis. The whole assessment aims at presenting bioenergy as an integral part of a sustainable energy strategy for India. The results show that bioenergy technology (BET) alternatives compare favourably with the conventional ones. The cost comparisons show that the unit costs of BET alternatives are in the range of 15-187% of the conventional alternatives. The climate change benefits in terms of carbon emission reductions are to the tune of 110 T C per year provided the available potential of BETs are utilized.

Problems and prospects in neurochemistry

The importance of neurochemistry in understanding the functional basis of the nervous system was emphasized. Attention was drawn to the role of lipids, particularly the sphingolipids,whose metabolic abnormalities lead to 'sphingolipidosis' In the brain and to gangliosides, which show growth-promoting and neuritogenic properties. Several questions that remain to be answered in this area were enumerated. It was pointed out that neurons make a large number of proteins, an order of magnitude higher than other cells, and several of these are yet to be characterized and their functional significance established. Myelination and synapto-genesis are two fundamental processes in brain development. Although much is known about myelin lipids and proteins, it is not known what signals the glial cell receives to initiate myelin synthesis around the axon, In fact, the process of myelination provides an excellent system for studying membrane biogenesis and cell-sell interaction. Great strides were made in the understanding of neurotransmitter receptors and their function in synaptic transmission, but how neurons make synapses with other specific neurons in a preprogrammed manner is not known and requires immediate study. In this context, it was stressed that developmental neurobiology of the human brain could be most profitably done in India. The importance and complexity of signal transduction mechanisms in the brain was explained and many fundamental questions that remain to be answered were discussed. In conclusion, several other areas of contemporary research interest in the nervous system were mentioned and it was suggested that a 'National Committee for Brain Research' be constituted to identify and intensify research programmes in this vital field.

The biology and pathogenesis of hepatitis viruses

Viral hepatitis is caused mainly by infection with one of the five hepatitis viruses, which use the liver as their primary site of replication. Each of these, known as hepatitis A through E viruses (HAV to HEV), belong to different virus families, have unique morphology, genomic organization and replication strategy. These viruses cause similar clinical manifestations during the acute phase of infection but vary in their ability to cause chronic infection. While HAV and HEV cause only acute disease with no chronic sequelae, HBV, HCV and HDV cause varying degrees of chronicity and liver injury, which can progress to cirrhosis and liver cancers. Though specific serological tests are available for the known hepatitis viruses, nearly 20% of all hepatitis cases show no markers. Antiviral therapy is also recommended for some hepatitis viruses and a preventive vaccine is available only for hepatitis B. More research and public awareness programmes are needed to control the disease. This review will provide an overview of the hepatitis viruses and the disease they cause.