# Bridging Disparate Structural/Functional Scales: Multiscale Modeling of Genome Organization and of Viral RNA Frameshifting > **NIH NIH R35** · NEW YORK UNIVERSITY · 2024 · $525,349 ## Abstract Abstract As advances in both experimental and computational biology lead to exciting discoveries in many fields of biology and biomedicine today, new avenues to diagnose and treat human disease are becoming a reality. Molecular dynamics and other simulation approaches play a key role in these connections by helping define the underlying biophysical mechanisms, at unprecedented resolution. The PI's computational biophysics lab focuses on solving fundamental structural and functional challenges concerning nucleic acids and their complexes (notably chromatin and RNA), in collaboration with experimentalists, by innovative molecular models and simulation methods using ideas from mathematics, computer science, engineering, biology, and chemistry. This MIRA project would continue to advance our fundamental understanding of genome organization and RNA motifs using multiscale models that bridge disparate spatial and temporal scales to generate biophysical insights into genome folding and cancer genomics, and RNA conformational landscapes/ viral mechanisms. For chromatin and chromosomes, modeled nucleosomes and their protein complexes at atomic resolution, and chromatin fibers at the mesoscale, will be linked to data from genome-wide and cancer epigenomics studies to determine the modulation of chromatin higher-order structure in processes of aberrant gene expression. Specifically, we will focus on the structural role and mechanisms of proteins (like CTCF and H1) in gene looping and formation of topologically associated domains (TADs) and nuclear compartments in gene activation or repression in cancer cells. For RNA, our topological approach to modeling RNA secondary structure by coarse-grained graphs (RAG: RNA-As-Graphs), combined with atomic biophysical modeling, will delineate programmed ribosomal frameshifting mechanisms in RNA coronaviruses and other viruses, and advance the RNA motif atlas. Specifically, conformational dynamics associated with the RNA frameshifting element of SARS-CoV-2, along with evolutionary and biophysical analysis and chemical reactivity experiments, will describe frameshifting transitions and identify/test experimentally structure-altering mutations that may hamper frameshifting. RAG will also be applied to define a virus topology atlas and explore virus motifs from an RNA repertoire point of view, to help understand the RNA motif universe and advance novel RNA design. The unraveled biophysical mechanisms in genome organization and RNA frameshifting/conformational repertoire have translational ramifications for human cancers and viral infections by coronaviruses or HIV. For cancer therapy, a targeted re-expression of silenced genes may be possible by chromatin topological changes (e.g., loop dissolution) and RNA editing. For viral RNA infections, new strategies for gene and anti-viral therapy emerge from this research, feasible by modern RNA editing technologies. The resulting multidisciplinary computational paradigms are widely appl... ## Key facts - **NIH application ID:** 10841601 - **Project number:** 5R35GM122562-07 - **Recipient organization:** NEW YORK UNIVERSITY - **Principal Investigator:** Tamar Schlick - **Activity code:** R35 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $525,349 - **Award type:** 5 - **Project period:** 2017-09-01 → 2028-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10841601 ## Citation > US National Institutes of Health, RePORTER application 10841601, Bridging Disparate Structural/Functional Scales: Multiscale Modeling of Genome Organization and of Viral RNA Frameshifting (5R35GM122562-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10841601. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*