# Mechanisms of nutrient acquisition by malaria parasite mosquito stages

> **NIH NIH R21** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $279,000

## Abstract

PROJECT SUMMARY AND ABSTRACT
 Plasmodium parasites cause the disease malaria. According to the World Health Organization there
were 216 million cases of the disease worldwide which led to 445,000 deaths in 2016. The disease is thus
formidable in its global burden and in an arena of malaria eradication and elimination, it is sobering to point
out that between 2015 and 2016, deaths from the disease only fell by 1,000. Furthermore, the frontline drug
treatment for uncomplicated malaria, artemisinin combination therapy, is beginning to fail due to the
emergence of drug resistant malaria parasites and thus the great gains in malaria control achieved over the
last decade could be wiped out in the near future. Novel interventions are thus still required.
 The malaria parasite has a complex life cycle, and in the case of the human disease, this relies on
both a mosquito vector and a human host. The mosquito vector transmits infectious sporozoites to the human
host which ultimately leads to a fulminant blood stage infection that causes all associated disease mortality
and morbidity. During the blood stage of infection, sexual blood stage gametocytes can be acquired by the
mosquito vector during blood meal acquisition where they mature into gametes. Gametes fuse to form a
zygote and then a motile ookinete within the mosquito midgut. The ookinete traverses midgut epithelial cells
before exiting through the basal side of the epithelium and develops as an extracellular oocyst, that is in
contact with the hemocoel cavity and its associated nutrition-rich hemolymph. Life in an extracellular
environment presents distinct challenges, and very little is known about how exactly the oocyst parasitizes its
mosquito host in order to mature and release sporozoites, which migrate to the salivary glands and lay in wait
for transmission to the next human host.
 Research has demonstrated that lipophorin, a lipoprotein complex derived from the mosquito
bloodmeal can be taken up by developing oocysts, likely for the purpose of providing lipids for sporozoite
production. However, whether this process is required for oocyst development is unclear. We have shown
that an oocyst-expressed ATP binding cassette (ABC) transporter plays a role in the uptake of lipophorin and
the deletion of the gene encoding this transporter leads to a severe defect in oocyst development, resulting
in a significant decrease in oocyst maturation and time to sporozoite release. This proposal aims to fully
elucidate the role of ABC transporters in oocyst maturation and their involvement in the acquisition of nutrients
required for sporozoite production. We will use reverse genetics, spatial and temporal expression analyses,
lipid labelling and heterologous expression to achieve these goals. An increased knowledge of this process
could aid in the development of novel intervention to target malaria mosquito stages.

## Key facts

- **NIH application ID:** 9964662
- **Project number:** 5R21AI146391-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Ashley M Vaughan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $279,000
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964662

## Citation

> US National Institutes of Health, RePORTER application 9964662, Mechanisms of nutrient acquisition by malaria parasite mosquito stages (5R21AI146391-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9964662. Licensed CC0.

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