Advances in high-speed computational platforms and innovative algorithms are opening op- portunities for modeling in biology as never before. While there are many general methods that can be applied widely, the most successful approaches are tailored and tightly connected with the application at hand. One such application area where a variety of models and methods — from atomistic to polymer levels — is critically needed to bridge experimental data involves the genome material, or the chromatin fiber in higher organisms.
Understanding and interpreting the structure and function of the genomic material in the live eukaryotic cells has been an enduring challenge in modern science. Indeed, the problem is as relevant today as when the Human Genome Project was being completed and questions about structure emerged following sequence.
As our appreciation for the diversity and flexibility of DNA on the base-pair level has deepened, its large-scale bending and coiling around histone proteins to form the chromosomal material in higher organisms has posed many structural and mechanistic questions. The genomic information in the DNA is packaged in a hierarchy of levels, from the nucleosome to condensed chromatin fibers to chromosomes and chromosomal territories. Thus, profound questions regarding DNA geometry, topology, and function span from the single nucleosome/base-pair level to condensed chromosomal arrangements on the mega-basepair level in the metaphase cell cycle. Associated structural transformations, tightly controlled by a host of proteins which can directly bind to the chromatin fiber or induce chemical modifications of DNA and histones, influence the global organi- zation of the chromatin fiber and hence a wide range of genome functions from cell differentiation to replication and transcription, to progression of human disease.
Though progress continues in our understanding of chromatin organization on the disparate length scales, a bridging between modeling and experimentation on the nucleosome and fiber lev- els with genome studies on the kilo-base level is lacking. New tailored multiscale computational approaches are needed to help interpret the rising volume of experimental data, especially those coming from genome-wide contact data. In addition, many mathematicians and physicists are working on relevant problems but there is a gap in resolution between the mathematical biology community’s coarse-graining approaches for DNA and chromatin fibers and the mathematical physics community’s polymer modeling on the order of chromosomes. Important biological ap- plications require an integration from the base-pair level to chromosome and genome wide scales, collaborative approaches, and strong interactions with experimental and medical scientists. Our program aims to bring these scientists together to discuss the current state-of-the-art in chromatin modeling, identify future challenges, and follow them with innovative multiscale, integrative approaches.
The dynamic structure of the nucleosome — approaches from molecular and coarse-grained modeling, atomic-resolution structural analysis and in-solution biophysical techniques — challenges and approaches;
The organization of the chromatin fiber as a function of internal and external parameters (linker DNA length and variations, linker histone concentration, salt environment, etc.) — merging experiment and theory;
The folding of the chromatin chain into chromosomes, connecting modeling with experimen- tal biophysics and biochemistry — merging genome-wide association data measurements with polymer and fiber modeling; and
Conference Week: March 16 - 20, 2020
The two organizers, Tamar Schlick (New York University) and Christos Likos (University of Vienna) are active researchers in the chromatin and polymer physics fields who approach problems on a broad range of modeling tools and some experimentation.
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