# Bridging Disparate Structural/Functional Scales: Multiscale Modeling of Genome Organization and if Viral RNA Frameshifting > **NIH NIH R35** · NEW YORK UNIVERSITY · 2024 · $125,000 ## Abstract Bridging Disparate Structural/Functional Scales: Multiscale Modeling of Genome Organization and of Viral RNA Frameshifting Project Summary May 22, 2024 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 continues 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 formation of gene loops, topologically associated domains (TADs), and nuclear compartments in gene activation or repression in cancer cells. For RNA, atomic-level biophysical modeling will be complemented by our topological coarse-grained graph approach for RNA secondary structures (RAG: RNA-As-Graphs) to delineate programmed ribosomal frameshifting mechanisms in RNA coronaviruses and other viruses, and advance the RNA motif atlas. Specifically, atomistic dynamics of the RNA frameshifting element of SARS-CoV-2, along with evolutionary and biophysical analysis and chemical reactivity experiments tailored to handle multiple RNA conformations will describe frameshifting transitions and identify/test experimentally structure-altering mutations that hamper frameshifting. We will also build 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, our structure-altering and motion-suppressing... ## Key facts - **NIH application ID:** 11098861 - **Project number:** 3R35GM122562-07S1 - **Recipient organization:** NEW YORK UNIVERSITY - **Principal Investigator:** Tamar Schlick - **Activity code:** R35 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $125,000 - **Award type:** 3 - **Project period:** 2017-09-01 → 2028-05-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/11098861 ## Citation > US National Institutes of Health, RePORTER application 11098861, Bridging Disparate Structural/Functional Scales: Multiscale Modeling of Genome Organization and if Viral RNA Frameshifting (3R35GM122562-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11098861. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*