# Polymer models of mitotic and interphase chromosomes

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $343,756

## Abstract

PROJECT SUMMARY
The spatial organization of chromosomes has long been connected to their polymeric
nature and is believed to be important for their biological functions, including the control
of interactions between genomic elements, the maintenance of genetic information, and
the compaction and safe transfer of chromosomes to cellular progeny. Chromosome
conformation capture techniques, particularly Hi-C, and microscopy have provided a
comprehensive picture of spatial chromosome organization and revealed new features
and elements of chromosome folding. Polymer models and new perturbation data
generated in the last two years have led to the identification of novel molecular
mechanisms behind large-scale genome organization. Two major mechanisms
discovered in the course of this project have moved the field forward. First, is the active
(ATP-dependent) process of loop extrusion by Structural Maintenance of Chromosomes
(SMC) complexes. This universal mechanism underlies formation of domains in the
interphase, and chromosome compaction and segregation in mitosis. Second, is the
affinity-mediated interactions between heterochromatic regions that drive spatial
compartmentalization of the genome at the scale of the whole nucleus. Proposed
project aimed at examining mechanisms of loop extrusion, understanding how gene
expression and affect extrusion and hence refold chromosomes, and, finally, developing
methods to detect loop extrusion in vivo by combination of polymer simulations and live
cell imaging. Together, these aims could show whether and how loop extrusion
operates in vivo, opening avenues to understand it functional roles and molecular
mechanisms.

## Key facts

- **NIH application ID:** 10476362
- **Project number:** 5R01GM114190-08
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Leonid A Mirny
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $343,756
- **Award type:** 5
- **Project period:** 2015-06-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476362

## Citation

> US National Institutes of Health, RePORTER application 10476362, Polymer models of mitotic and interphase chromosomes (5R01GM114190-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10476362. Licensed CC0.

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