Mutations in transcription factors can have pleiotropic and unpredictable effects since they may impact many genes in many cell types, yet their direct target genes may differ in each cell type. The goal of this project is to generate a general framework for understanding the cell-type specific effect of any given patient-specific mutation in transcription factors studied by the consortium and elsewhere, with a focus on NFkB. The Zaugg group has recently developed a tool to generate cell-type specific gene regulatory networks, which are based on connecting transcription factors to enhancers to their target genes. In previous work, we have found that many TFs, including NFkB, regulate a very cell-type specific set of genes.
In this project we aim to understand the impact of NFkB mutations in different immune cell types.
This project is part of the MSCA-funded doctoral network IMMERGE: STORMING IMMUNE MONOGENIC CONDITIONS THROUGH MULTIOMIC AND GENE EDITING APPROACHES.