May 14, 2010
Epigenomic Modifications in Neurodevelopment
NAMHC Concept Clearance
Michelle P. Freund, Ph.D.
Chief, Molecular Biotechology Program
Scientific Program Coordinator
Office of Cross Cutting Science and Scientific Technology
Division Neuroscience and Basic Behavioral Science (DNBBS)
This initiative solicits research to identify the developmental and tissue specific targets of epigenetic regulation resulting from environmental and social stimuli and to identify the components of the signaling pathway(s) that link stimuli to gene regulation and subsequent phenotypic variability. Priority will be placed on studies that examine marks across species and/or studies that address heterogeneity of epigenetic marks across tissue types, including cell specificity in the brain and across development. The primary objective is to gain insight into critical windows of plasticity in neural development.
Epigenomic mechanisms impact gene activity without altering the DNA code and consist fundamentally of DNA methylation and regulation of chromatin structure through post-translational modification of histones and other factors. Although these are reversible biochemical modifications, they can have lasting effects that are heritable within a cell lineage and possibly across generations. Research supported by this initiative will focus on epigenomic plasticity during development and how modifications translate into changes in neural architecture and function. Further, this initiative will focus on how early experiences and the environment impact the epigenome which, in turn, may influence the risk of developing mental disorders. Comparison of data from multiple species, with exposures to different environmental stimuli, throughout development will provide an understanding of the impact of epigenetic regulation on neuro-architecture, and the interaction of the epigenome with the genome’s primary sequence. Examples of research to be encouraged include:
- Develop a deeper understanding of specificity of epigenomic marks across development and tissues, including studies that examine the validity of peripheral markers as accurate indicators of brain epigenomic changes and potential functional implications.
- Gain insight into the mechanisms by which early experiences and environmental influences are translated into epigenomic changes that mediate developmental plasticity during sensitive periods.
- Integrate epigenetic data with the Transcriptional Atlas of Human Brain Development as an additional source of information about phenotypic variation.
- Increase understanding of the mechanisms that confer cell-specific epigenetic changes that regulate developmental outcomes.
- Identify epigenetic marks that may serve as novel diagnostic tools for the molecular basis of disorders and thereby inform rational drug design for therapeutic interventions.