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  • The Accelerator program for Discovery in Brain disorders using Stem cells (ADBS)

The Accelerator program for Discovery in Brain disorders using Stem cells (ADBS)

 

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Mental illness, which arises from alterations in normal brain function are a major source of disability in young adults.  About 2-3% of the population is at risk for developing these disorders both in India and across the world. These disorders are recognized as one of the major non-communicable diseases (NCD) and a significant contributor to morbidity as articulated by the New Delhi call for action on combating NCDs in India. Given the large number individuals affected by mental illness, the development of new methods to diagnose and treat mental illness is likely have important, positive social and economic benefits. In addition studies of mental illness may shed light of the normal functions of the brain, a major challenge in modern science.

Mental illnesses are slowly progressing chronic conditions that are now considered to be neurodevelopmental disorders. Despite their high heritability and the identification of a large number of ‘common’ and rare DNA sequence variants, few genetic correlates that could account for their high prevalence have been identified. Many of the genes (and pathways) identified suggest aberrant neural development and connectivity in early life as being critical to their pathogenesis; however this remains to be tested.  It is thought that environmental factors acting through epigenetic mechanisms will alter brain development leading to recognizable syndromes of clinically, abnormal behavior.

Given the gene/environment interactions that over time are likely lead to mental illness, well-identified, prospective clinical cohorts offer a unique opportunity to understand how mental illness develops. The Department of psychiatry at NIMHANS has been identifying and following families with a high incidence of psychiatric disorders over several years and have been conducting research into many clinical aspects of these diseases. In this program will plan to initiate and follow prospectively a cohort of individuals from such clinically dense families. They will be followed over a period of twenty years in order to observe the development of clinical disease and assessed using a range of clinical investigation including neuroimaging and neuro-psychological assessments at regular intervals this period.  In order to understand the potential cellular and molecular basis of altered brain function in these individuals, we will also establish pluripotent stem cell lines from these individuals. This material will be used to generate cellular models (disease in a dish) in which mechanistic aspects of cellular neurobiology that may lead to disease can be studied in detail. This work will be done at NCBS & inStem who have a shared interest in fundamental neurobiology as well as established expertise in genetics and cell biology including the ability to generate neuronal cell models using state of the art stem cell technology.

Collectively, the ADBS program aims to understand the relationship between cellular phenotypes and disease progression in the context of mental illness. through collaborative research applying genetic analysis and cell-based assays on patient derived cell lines in conjunction with information from detailed clinical analysis in human patients.

The ADBS program is supported by the Department of Biotechnology, Government of India and the Pratiksha Trust, a charitable trust set up up Kris Gopalakrishnan, co-founder of Infosys and his family. 

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