# Genome Folding and Regulation in Diploid Multicellular Organisms

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT STORRS · 2022 · $402,500

## Abstract

PROJECT SUMMARY / ABSTRACT
A functional multicellular organism consists of various cell types that arise from a single cell. This fascinating
process involves changes in spatio-temporal gene activity and genome organization. Disruptions in
chromosomal interactions and gene expression can lead to developmental disorders or cancer. Despite the
remarkable emerging views on multi-scale genome architecture and gene regulation, our knowledge is still very
limited on how maternal and paternal genomes are accommodated in each cell to achieve diverse cellular
identities. Moreover, it remains poorly understood how structural heterozygosity between parents may impact
genome structure and function to tip over cell state from normal to dysfunctional. Challenges in distinction
between homologous chromosomes, especially at single cell resolution, have hampered our ability to ask
pressing questions about variability and heterogeneity of parental genomes and related functional significance.
Our previous work involved the development of complementary approaches including haplotype-specific omics
and transformative single-cell imaging to distinguish homologs. Our goal is to leverage these powerful
approaches to determine how packaging and functional regulation of diploid genomes are formed and
maintained, and how disrupted genome integrity affects cell fate. Specifically, we will determine how parental
contribution influences intricate early genome packing and regulation. Furthermore, we will investigate plasticity
in establishment and maintenance of single-cell identities within tissues. Finally, we will uncover how
heterozygosity in parental content including transposons affects genome integrity, and thereby increase our
understanding of parental genome compatibility and organismal viability. Together, these proposed studies will
provide an enhanced framework for our foundational understanding of parental chromosome folding and
regulation to better interpret contribution of dysfunctional chromosomes to disease.

## Key facts

- **NIH application ID:** 10498184
- **Project number:** 1R35GM146922-01
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Jelena Erceg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,500
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498184

## Citation

> US National Institutes of Health, RePORTER application 10498184, Genome Folding and Regulation in Diploid Multicellular Organisms (1R35GM146922-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498184. Licensed CC0.

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