The rates of nearly every molecular process involved in gene transcription can be altered by chromatin nanoenvironment. In order to mechanistically link chromatin packing, 3D genome structure (e.g. gene contact probabilities), and gene transcription, from the first principles of physics, in collaboration with Prof. Igal Szleifer we develop multi-scale computational and analytical predictive tools. The platform bridges molecular dynamics, molecular theory, the Brownian Dynamic simulations, and the coarse-grain modeling at the chromatin level. Chromatin imaging enabled by the nanoimaging platform informs the computational transcriptomics platform, whose predictions are then cross-validated by molecular analysis genomic technologies.
Using the combination of the nanoimaging and computational transcriptomics platforms we study how chromatin packing density scaling regulates cells’ ability to explore their transcriptional landscape. This modulates the barrier for functional changes to occur with implications for a variety of processes including cellular differentiation, stem cell processes, tissue regeneration after an injury such as ischemia and infarction and diseases where dynamic adaptation and/or transcriptional reprogramming plays a critical role such as cancer, atherosclerosis, and neurodegeneration.
Collaborator: Prof. Igal Szleifer
Highlight Paper: “Macrogenomic engineering via modulation of the scaling of chromatin packing density”, Nature Biomedical Engineering, doi: 10.1038/s41551-017-0153-2 (2017). PMC5809134.