Prof. Brahmachari, recognized as distinguished alumni from the school of Molecular Biophysics at Indian Institute of Science, received his early training in structural biology of proteins and polypeptides. He has made outstanding contributions in understanding the role of repetitive DNA in genome function in health and disease. He visualized the integration of structural biology with genomics, molecular biology and information science forging towards integrative biology. Prof. Brahmachari made fundamental discoveries in demonstrating the structural flexibility of DNA and the role of repetitive sequences in DNA transactions much before the discovery of repeats association with genetic basis of several neurological disorders [1-6]. His work on the structural flexibility of telomeric repeat sequences is one of his well cited pioneering contributions, which has led others to develop approaches for cancer therapeutics [4-6]. He sought to understand the functional relevance of repetitive DNA in clinical context that resulted in extensive collaboration with a large number of clinicians and also in motivating young physicians to undertake research in genomic sciences. Through a combination of directed research, he seeded functional genomics research in India, moving away from the prestigious Indian Institute of Science, Bangalore, to found the CSIR- Institute of Genomics and Integrative Biology in Delhi. Prof. Brahmachari has made major contributions in molecular analysis of genetic disorders associated with trinucleotide amplification and repetitive sequence instability. Using a combination of structural biology, computational genomics and population based polymorphism scanning, he and his group have provided a novel structural frame work for understanding the etiology of several neurological disorders. One of the outcomes of these efforts has been the demonstration that loss of triplet repeat interruption as the primary steps in ataxia SCA 2 which is followed by repeat expansion [7-9]. In addition, he has made major contribution in identifying founder chromosomes of several Spino Cerebellar Ataxia and Huntington’s Disease in India. Repeat polymorphism in the genome and variation in coding sequences reflected in these diseases brought an insight into the balancing act of nature between variation and conservation. This eventually led to his conceptualization and execution of the Indian Genome Variation project. Prof. Brahmachari has established the CSIR Indian Genome Variation Consortium Project for predictive and personalized medicine with a team of 150 researchers including scientists and students to provide the first comprehensive genetic map of the extremely diverse Indian population with different evolutionary history, comprising thousands of endogamous populations and hundreds of functioning languages [14]. The execution of the project was strategically planned with the development of innovative cost-effective methods and suitable private-public partnerships. A major discovery has been that despite enormous diversity, the populations of India could cluster into 5 major groups [15,16,18] . This has been enormously useful in designing a large number of studies that aim to identify predictive markers for complex diseases and pharmacogenomics studies. The basal data has also been useful in tracing migration history of populations; the most striking has been the sampling of Asian populations, identifying risk haplotype for carrier detection and also discovering signatures of selection for as in the case of high altitude adaptation. Under his leadership, the Institute (CSIR-IGIB) rose to the forefront of clinical genomics in India, addressing nationally important problems such as identifying risk markers for pulmonary edema in soldiers posted at high altitudes. In many diseases of relevance to the Indian people, such as asthma, diabetes, cardiovascular disease, and schizophrenia, he master-minded the development of translational research programs in concert with clinical institutions. This set the stage for inter-institutional collaborative research, which had been largely missing before. Prof. Brahmachari leveraged the angle of personalised medicine towards pharmacogenomics with focus on affordable healthcare. Parallel with the Indian Genome Variation Consortium project, a unique initiative called Ayurgenomics has been conceptualized and supported by Prof. Brahmachari. This project aims to integrate the principles of personalized medicine from Ayurveda, an ancient Indian medical system with modern genomics to bridge the gap from genotype to phentoype. The first proof of concept that healthy individuals classified on the basis of constitution types described in Ayurveda exhibit differences at the biochemical and genomic level was provided by his group [17]. While variation was the key in genotype to disease phenotype, Prof. Brahmachari explored the importance of conservation in non-coding RNA. Prof. Brahmachari is one of the pioneers in proposing a role for microRNAs in host-pathogen interactions [11]. He and his coworkers identified human microRNAs targeting HIV-1 and predicted its implications in disease progression and potential antiviral activity and validated experimentally [11,13] . This paradigm of microRNAs and microRNA regulatory networks were proposed in host-pathogen interactions [12]. He and his co-workers also developed a computational methodology to understand the impact of genomic variation in the 3’-untranslated regions of coding genes in the genome could have potential functional implications. Prof. Brahmachari organized a vibrant team of researchers with complementary expertise to understand non-coding RNA regulation from mechanistic to the therapeutic level. In the context of gap in genomics to drug discovery Prof. Brahmachari believes that “when it comes to health, we need to have a balance between health as a right and health as a business”. Open Source Drug Discovery (OSDD) [20] initiative was Prof. Brahmachari’s brainchild, and today it is being considered as perhaps CSIR’s boldest and most path breaking initiative in its sixty years plus history. The goal of the initiative is to enable open, collaborative scientific research that will make possible the discovery and development of new Prof.ugs. Its aim is to provide extremely affordable healthcare for the resource poor people across the world by creating ultra-low-cost drugs. Despite the availability of Mycobacterium tuberculosis (Mtb) genome for almost a decade no promising drug has seen the light of the day, suggesting a gap in our understanding of M. tuberculosis biology. Prof. Brahmachari synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D) and developed an open collaborative web-based platform to generate the most comprehensive interactome of Mtb, the 'interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Prof. Brahmachari & associates further combine IPW network with STRING based network and use network analysis to report central proteins which may be assessed as potential drug targets for development of drugs with least possible side effects. Considering his exceptional contribution, Prof. Brahmachari has been bestowed with the title of “Open source Guru ” for conceptualizing and mentoring India’s first crowd – sourcing initiative – Open Source Drug Discovery and has also been recently nominated as one of Fierce's Top 10 Biotech Techies for his outstanding contribution to the field of genomics and open source drug discovery. As of now, Prof. Brahmachari’s OSDD model is going to be used primarily to develop extremely affordable drugs required by resource poor patients all around the world. However, OSDD has already demonstrated the power of galvanizing the collective imagination and creativity of ‘anyone, anytime, anywhere’ and especially the young, like never before. Therefore, Brahmachari’s successful OSDD raises the hope of achieving the illusive goal of ‘health for all’. |
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