A Systems Biology Approach to Identify Transcription Regulatory Networks in Healthy and Diseased Neurons
2013 Seed Grant

Yingxi Lin, Ph.D.
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology

In neuropsychiatric disorders such as autism, very different genetic mutations can give rise to similar behavioral and cognitive deficits. This genetic heterogeneity not only makes it difficult to understand disease etiology, it also demands the development of a strategy in drug discovery that targets a process that is affected similarly by different genetic mutations. As behavioral outputs are determined by the process by which neural circuits are formed and modified during development in response to sensory experience, the behavioral similarity seen in diseases suggests that identifying key molecular and cellular features of the development process that are representative of different disease states may prove to be very valuable in their diagnosis and treatment. An essential requirement for neural circuits to integrate sensory experience and convert it into permanent behavioral changes is the activation of neural activity-dependent transcription programs. Dr. Lin and her lab hypothesize that the functionality of neural circuits is reflected in the input-output relationships of the activity-dependent transcription regulatory networks, thus, functional or dysfunctional states of the neural circuits can be detected by analyzing the underlying transcription programs. They propose to adopt a systems biology strategy to construct a transcription regulatory network model that can be used to differentiate between healthy and various diseased neurons. Dr. Lin’s proposed approach will not only help us gain deeper understanding of disease mechanisms of neuropsychiatric disorders, it may also facilitate disease diagnosis and drug discovery.

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