Aim 1. Tools for Cell Circuit Reconstruction: Experimental Methods

We propose to create an experimental toolkit for unbiased studies of cell circuits, addressing several unmet needs. First, we will develop methods to genomically profile not only nucleic acids (mRNA, DNA) and their interactions, but also proteins and their modifications.  

Aim 2. Tools for Cell Circuit Reconstruction: Computational Methods

We will build and distribute a suite of algorithms and tools needed for circuit reconstruction. First, we will create methods for analyzing raw data from genomics and proteomics experiments. 

Aim 3. Cell Circuit Reconstruction: Innate Immune Responses to Pathogens In Dendritic Cells -Multi-layer Control of Signaling and Transcription

We will generate a multi-layered, integrated circuit of an environmental response in a mammalian cell specifically in the immune dendritic cells that detect pathogen-derived molecules and induce appropriate immune responses.  

Aim 4. Cell Circuit Reconstruction: Stem Cell Renewal and Differentiation - Transcriptional and Epigenetic Regulation by Proteins and lincRNAs

We proposed to decipher the chromatin regulatory circuit of embryonic stem cells, focusing on the protein and RNA complexes that catalyze histone modification and/or physically interact with modified histones. 

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