The workshop will address an emergent interdisciplinary research area that will in the long term result in the development of new strategies for reversible regulation or engineering of the systems of gene expression to modulate the function of a living organism. The behavior of organisms is determined not only by their genetic code but also by their capacity to explore a transcriptional landscape of thousands of genes to create new functional states. Genetic engineering techniques such as CRISPR-Cas9 have recently emerged to edit specific genes. The next frontier is building the fundamental understanding of the principles of complementary strategies for transcriptional engineering. Gene transcription regulation occurs across a hierarchy of length scales: from the nucleosomal level through alterations in local DNA accessibility (~10nm) to genome compartmentalization conferred by organization of DNA into a range of domains (~100nm) and to chromatin packing, which works across all supranucleosomal length scales (>10nm) and affects global patterns of gene expression. It is becoming increasingly accepted that gene transcription is influenced not only by targeted molecular but also by systems-level physical factors. For example, gene expression is a series of interrelated chemical reactions that depend on the complex chromatin nanoenvironment (e.g. nanoscale-local ionic environment, pH, molecular crowding), which in turn affects and is being affected by chromatin compartmentalization and packing. Decoding these processes and designing strategies to regulate them can only be achieved through "convergent science" that bridges otherwise disparate research fields, including molecular biology, physics-based modeling of transcriptional molecular processes, computational genomics, systems biology, and nanoscale imaging.
The potential payoff of such research is substantial: examples of biological processes involving global genomic reprogramming include stem cell plasticity, tissue regeneration, and diseases such as cancer, atherosclerosis, and neurodegenerative diseases. Precise regulation of cells, not merely through genetic manipulation or histone modifications but also through engineering changes at the level of genome compartmentalization and chromatin packing, may enable us to combat disease and design organisms that can remediate environmental problems or adapt to environmental change. The significance of this frontier topic is further recognized by being listed by National Science Foundation as one of NSF's 10 Big Ideas for Long-term Discovery and Innovation and being selected as one of the two topics for NSF's highly prestigious Engineering Frontiers in Research and Innovation (EFRI) program, which identifies research areas of both high innovation and significance for the future of engineering.
This workshop was conceived to bring together experts from a variety of fields of molecular science that would not otherwise have a forum to meet, including biomolecular scientists, physicists, "big data" experts, molecular biologists, and engineers. The topics will be highly interdisciplinary and include the 4D nucleome (e.g. chromatin compartmentalization and packing), physics-based modeling of genomic molecular processes (e.g. molecular dynamics modeling), nanoscale imaging of the genome (e.g. electron microscopy tomography, optical superresolution nanoscopy), and transcriptional engineering with applications. This is an extremely rapidly developing field with several key award-winning enabling technologies being developed only in the past few years (e.g. superresolution microscopy, chrom-electron microscopy tomography, chromosome conformation capture) and with what used to be viewed as "well-accepted" concepts being continuously overturned. TSRC's mission and ethos is an ideal match for such a convergent science forum given the fast pace of technological innovation and the potential significance of this frontier research.