Center for Cell Circuits

Artwork by Sigrid Knemeyer. Original micrograph image by Alex Shalek.

Rationale. As genome sequencing becomes routine, a plethora of disease-associated gene alleles have been revealed. These increasingly powerful genetic approaches, however, have not been matched by comparable systematic methods to place genes into cellular circuits. Without such methods, it will be difficult to decipher the mechanisms underlying the effects of alleles on phenotype, and to develop treatments based on genetic defects. 

Goals. The central goal of the Center for Cell Circuits is to create the critical reagents, technologies, protocols and strategies needed to reconstruct molecular circuits. Our experience to date suggests that it should be feasible to develop, apply and iteratively refine a universal strategy for circuit reconstruction and perturbation at increasing resolution in the next few years. To motivate this program, we focus on two distinct and complementary mammalian circuits – the transcriptional response to pathogens in immune dendritic cells (DCs) and the regulation of epigenetic states in embryonic stem (ES) cells. 

Implications for genomic sciences and disease biology. First, the suite of genome-scale tools and strategies created by our center should be useful in the analysis any mammalian cell circuit, helping any researcher to dissect their own biological system in detail. Second, the detailed reconstructed circuits we generate represent a community resource that suggests solutions for specific open problems in the relevant fields, including mechanisms of immune and stem cell-related disorders and therapeutic strategies. Finally, our measurement and perturbation experiments will provide the computational community with some of the most comprehensive datasets in mammals that can serve as training and validation datasets for new algorithms.

The Center for Cell Circuits at the Broad Institute is a Center of Excellence in Genomic Science (CEGS), a program established by the National Human Genome Research Institute for multi-investigator, interdisciplinary research that develops novel and highly innovative genomic research projects.

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