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
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.