Team Leader National Centre for Biological Sciences Bangalore, Karnataka, India
Abstract: Severe mental illness (SMI) is a significant cause of disability worldwide affecting 1 in 8 people worldwide. The clinical management of these patients poses significant challenges both in terms of diagnosis and the availability of therapeutic agents and better tools are needed in both these domains. The development of such tools in turn would be facilitated by a better understanding of the aetiology of these illnesses as well as the cellular and developmental alterations in the brain of these patients.
Both genetic and environmental factors are known to contribute to the development of SMI. Although known to be polygenic, the genetic loci involved are not well understood. Likewise due the non-accessibility of human brain tissue to biopsy, studying cellular changes associated with SMI has not been possible. In order to address these challenges, the Centre for Brain and Mind has assembled a prospective cohort of clinically dense families affected by some of the key SMI (schizophrenia, bipolar disorder, obsessive compulsive disorder, substance dependence and dementia). The program includes three verticals (i) clinical characterization of affected patients along with unaffected family controls at multiple levels of brain structure and function at 3 years intervals over a 20 year period (ii) genetic analysis of cohort members using next generation sequencing and informatics (iii) generation of a biorepository of patient and control derived induced pluripotent stem cells (iPSC). This last vertical is expected tp facilitate the cellular and developmental analysis of the brain using 2D and 3D brain organoid models. To date the program has generated a collection of ca. 120 iPSC lines which along with the relevant metadata are available for “disease-in-a-dish” analysis of SMI. Genome engineered reporter lines derived from these iPSC have also been generated to facilitate the analysis of key sub-cellular and molecular processes in various human brain cell types in SMI. The availability of this comprehensive resource is expected to facilitate an enhanced understanding of altered brain structure and function, in turn leading to the development of better diagnostics and therapeutics for SMI.
Funding Source: The Centre for Brain and Mind is supported by Rohini Nilekani Philanthropies. Full details of the program can be found at https://www.ncbs.res.in/cbm/home
