# Project 4 Genomic and transcriptomic interactions between malaria parasites, their mosquito vectors, and human hosts at the scale of continents, villages, and single cells

> **NIH NIH U19** · BROAD INSTITUTE, INC. · 2021 · $608,142

## Abstract

Malaria, caused by protozoan parasites in the genus Plasmodium and transmitted by Anopheles mosquitoes,
is a disease of critical importance to global public health. The premise of our proposal is that genomic
resources and technology development have the potential to greatly contribute to the renewed malaria
elimination effort through enhanced biological and epidemiological understanding. The work described
in this study will advance our understanding of parasite/vector interactions, parasite/human interactions, vector
evolution, and parasite genomic epidemiology.
AIM 1. Develop a major population genomic resource for Neotropical anopheline malaria vectors.
We will generate two significantly improved reference genome assemblies for An. darlingi, the most important
vector in the New World, and perform resequencing-based population genomic studies of An. darlingi and
other neotropical malaria vectors to identify cryptic species boundaries and population structure that could
impact traits contributing to vectorial capacity.
AIM 2. Profile the comparative population genomics of malaria parasites in low-transmission settings
in West Africa and the Neotropics. Malaria parasites in low-transmission settings typically face distinct
challenges from parasites in more highly endemic zones, including reduced host immunity, reduced intra-host
competition, higher access to treatment, and concomitantly more consistent selection pressure from drugs.
We will perform whole genome sequencing of thousands of P. falciparum parasites from low-transmission
settings in the Neotropics and West Africa to identify common as well as distinct population genomic
signatures of adaptation and transmission dynamics
AIM 3. Identify parasite genes that mediate interactions with mosquito vectors by sequencing a unique
sample collection from Gabon. Malaria parasites and anopheline vectors are known to adapt to each other,
sometimes on very local geographic scales. We will search for parasite loci that mediate this adaptation by
sequencing Plasmodium falciparum from infected mosquitoes collected in Gabon, West Africa, a region where
at least 15 anopheline species serve as vectors for three human malaria parasite species.
AIM 4. Define the transcriptional profile of the human host and Plasmodium parasites in single infected
hepatocytes. The key biological difference between P. falciparum and P. vivax is the capacity of the latter
species to remain in a metabolically dormant hypnozoite state within the liver for weeks, months, or years,
impervious to most drug treatments. We will study how host and parasite genes are regulated within individual
infected hepatocyte cells.
This work will influence the field through the generation of novel genomic resources and methods,
new biological insights, and innovative analytical methods.

## Key facts

- **NIH application ID:** 10163680
- **Project number:** 5U19AI110818-08
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Daniel E Neafsey
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $608,142
- **Award type:** 5
- **Project period:** 2014-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163680

## Citation

> US National Institutes of Health, RePORTER application 10163680, Project 4 Genomic and transcriptomic interactions between malaria parasites, their mosquito vectors, and human hosts at the scale of continents, villages, and single cells (5U19AI110818-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163680. Licensed CC0.

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