# Evolution of the 3D chromatin structure in apicomplexan parasites

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $248,117

## Abstract

Abstract
 Control of gene expression in eukaryotic organisms has been extensively studied in a broad range of
experimental systems, including the apicomplexan parasites responsible for several human diseases. Changes
in the three-dimensional (3D) organization of chromosomes within the nucleus has been associated with
changes in gene expression in model organisms, although whether alterations in subnuclear chromosome
structure are causative or simply associated with transcriptional changes is a matter of debate. Similar
phenomena have been reported by a number of groups studying Plasmodium, the genera of parasites
responsible for malaria in both humans and animals. For example, perinuclear clusters of the subtelomeric
chromosomal domains have been observed in P. falciparum and linked to control of expression of variant
antigen encoding genes. However, definitive evidence defining the role of 3D arrangement in regulating gene
expression, including gene involved in antigenic variation or virulence factors in eukaryotic pathogens are
limited.
 Here we propose to explore the hypothesis that 3D, higher-order chromosomal organization evolved in
parasites of primates to help coordinate monoallelic variant gene expression. We recently performed
comparative studies on subnuclear chromosomal organization in different species of malaria parasites and
found that parasites that infect primates display a unique, highly complex organization not observed in malaria
parasites of rodents. We have also recently created several genetically modified lines of P. falciparum that have
significant changes in specific elements proposed to be involved in chromosomal organization. Several of these
modifications have profound effects on expression of genes involved in antigenic variation. We will use these
resources to investigate how epigenetics features and chromosome organization are maintained in
apicomplexan parasites as well as their role in coordinating expression of large, multicopy gene families, such
as var genes. We will perform the following two specific aims. In AIM 1, we will characterize the evolution of
3D chromatin structure in apicomplexan parasites by performing Chromosome Conformation Capture (Hi-C)
experiments to analyze the spatial organization of chromosomes for several parasites of the apicomplexan
clade. We will also use genetically altered parasite strains to identify DNA sequence elements involved in 3D
chromosomal organization. In AIM 2, we will investigate a possible link between 3D higher-order
chromosomal organization and monoallelic variant antigen expression in primate Plasmodium species by
analyzing genetically altered parasites with deletions of regulatory elements that alter monoallelic variant
antigen (var) expression. The results of this work will be transformative for our understanding of chromatin
structure's role in parasite gene expression, virulence and disease. Our main goal is to design novel
intervention strategy targeting chromat...

## Key facts

- **NIH application ID:** 9832685
- **Project number:** 5R21AI142506-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Karine Gaelle Le Roch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,117
- **Award type:** 5
- **Project period:** 2018-12-07 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832685

## Citation

> US National Institutes of Health, RePORTER application 9832685, Evolution of the 3D chromatin structure in apicomplexan parasites (5R21AI142506-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832685. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*