We combine:
3D Genome Architecture
Super-Resolution Live-Cell Imaging (SRLCI)
Computational approaches such as polymer simulations
Differentiation in clinically relevant tissues
These are example of biological research questions that we aim to address:
1) What are the mechanisms of Enhancer promoter interactions durin differentiation, who are they established and maintained?
2) What is the direct role of chromatin modifications in mediating EPIs?
3) How do chromatin regulators facilitate the formation of EPIs during differentiation and are they involved in starting and/or maintaining these interactions?
4) How do we engineering EPIs to fine-tune dysregulated gene expression?
Enhancer-Promoter Interactions are responsible for fine tuning gene expression regulation in response to stimuli, in different tissues, and at different developmental stages. Identifying the molecular mechanisms of EPI for genes of interest is the first step towards restoring their physiological levels and understanding the direct role of other proteins involved in EPI regulation.
Germline mutations in chromatin regulators often lead to neurodevelopmental disorders. Moreover, chromatin regulators are among the most frequently mutated genes across most tumors. Chromatin regulation and enhancer-promoter interactions are essential to establishing and maintaining cell identities. When these processes are dysregulated, they lead to pathological conditions.
Lawrence et la., Nature, 2014
Example of 3D super-resolution live cell imaging (SRLCI) experiments, choice of biological system, and experimental design.