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INTERMODULE INTEGRATION--PLASTICITY /ROBUSTNESS IN BRAIN

$196,651P50FY2006GMNIH

Harvard University, Cambridge MA

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Abstract

The study of modularity in biological systems is mostly concerned with molecular and cellular networks and pathways in single cells. Although we can describe and analyze modules at all levels of biological organization, the ultimate challenge facing systems biology is the integration of complex processes across many levels, from molecules to whole organisms in an ever-changing environment. We propose here to begin building such a comprehensive framework for understanding complex and phenotypically plastic traits as they result from interactions between genotype and environment. Over the past several years, we have developed a model system, the African cichlid fish Astatotilapia burtoni, in which we can measure both behavior and physiological processes in semi-natural conditions. In a social community of A. burtoni, there is a constant exchange of social information as males establish territories, court females and make aggressive displays towards other males. We have shown previously at the molecular, neuroanatomical, and endocrine level that social status regulates reproductive state, growth rate, and stress reactivity. In this proposal we will (1) construct an annotated cDNA microarray representing >10,000 A. burtoni genes and ESTs; (2) determine how tissue-specific gene expression profiles differ between dominant and subordinate A. burtoni males; and (3) uncover how these profiles change during changes in social status. Furthermore, we will begin a rigorous and systematic functional analysis of genes we find to be involved in plasticity. Our analysis will determine whether dedicated modules underlie plasticity organismal robustness, or whether they are consequences of the actions of other pathways and networks.

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