# Determining the interactions between mosquito oogenesis and Plasmodium falciparum survival and transmission

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2022 · $768,986

## Abstract

PROJECT ABSTRACT
Anopheles gambiae females are the most important vectors of human malaria in sub-Saharan Africa. During
their lives, these females feed on blood several times to undergo multiple gonotrophic cycles of egg
development and egg laying. These reproductive cycles, largely orchestrated by the steroid hormone 20-
hydroxyecdysone (20E), are exploited by Plasmodium falciparum parasites for transmission between human
hosts. The time required for parasite development—from ingestion of male and female gametocytes to
sporozoite invasion of salivary glands—is called the Extrinsic Incubation Period (EIP) and is a key factor in
malaria transmission dynamics, especially when considering the limited lifespan of mosquitoes. Despite its
relevance for parasite transmission, the link between parasite development and oogenesis has not been fully
explored, and important questions such as whether Plasmodium survival and growth depends on pathways
that promote egg development are still largely understudied.
In a recent study, we revealed substantial physiological links between P. falciparum development and
An. gambiae reproductive processes that shape oogenesis. We have unveiled an unexpected positive
correlation between egg and oocyst numbers and have shown that, in instances where 20E function is
impaired, reduced oogenesis induces a decrease in parasite intensities. Manipulating egg development by
these and other 20E-independent means, however, accelerates Plasmodium growth rates, shortening the
EIP and allowing sporozoites to become infectious sooner. Faster growth depends on the accumulation of
blood meal-derived midgut lipids trafficked to the ovaries by the lipid transporter Lipophorin (Lp). Our
outstanding questions concern the mechanisms by which 20E-regulated oogenetic processes affect parasite
numbers, and how the EIP is affected by egg development and Lp-transported lipids in the natural context of
multiple gonotrophic cycles. Preliminary evidence suggests that the mis-regulation of 20E signaling may
cause parasite death via oxidative stress and/or apoptosis. Moreover, we show that an additional blood meal
significantly accelerates parasite growth, while our initial field infections in Burkina Faso suggest the EIP is
regulated by parasite genetic determinants. Here we will perform lab and field studies to determine how
oogenesis impacts the biology of P. falciparum in the An. gambiae female, from establishment of
infection to sporozoite transmission and across multiple reproductive cycles. Specifically, we will: Aim
1) determine the fundamental mechanism by which parasite numbers are reduced when egg development is
impaired; Aim 2) analyze how a second gonotrophic cycle affects the EIP and sporozoite infectivity to human
hepatocytes; and Aim 3) determine in field infections whether the EIP is regulated by parasite genetic factors.
This project will not only fill critical knowledge gaps in mosquito-parasite interactions but will also provide
cr...

## Key facts

- **NIH application ID:** 10412958
- **Project number:** 5R01AI153404-03
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Flaminia Catteruccia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $768,986
- **Award type:** 5
- **Project period:** 2020-06-11 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412958

## Citation

> US National Institutes of Health, RePORTER application 10412958, Determining the interactions between mosquito oogenesis and Plasmodium falciparum survival and transmission (5R01AI153404-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10412958. Licensed CC0.

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