# Molecular mechanisms of Plasmodium fertilization

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $409,375

## Abstract

ABSTRACT
Malaria remains one of the most devastating infectious diseases. It kills over a million people
every year while causing immense suffering and economic losses worldwide. Whereas much
progress has been made in understanding the life cycle of the parasite in the human host and in
the mosquito vector, significant gaps of knowledge remain. Fertilization of malaria parasites is a
poorly understood process that takes place in the lumen of the mosquito gut. This process is
important because survival in nature is completely dependent on the ability of the parasite to
undergo sexual reproduction.
The proposed research aims to identify molecular interactions that take place during fertilization
of malaria parasites. This project is based on an unorthodox approach (identification of peptides
that bind to the gamete surface) made possible by the recent development of an important tool,
a transgenic parasite that produces red-fluorescent female gametes and green-fluorescent male
gametes. Pure populations of malaria female and male gametes from this transgenic parasite
were isolated by cell sorting and then used to screen a phage display library for peptides that
recognize molecules on the gamete surfaces. A peptide (FG1) that binds to female gametes
and another peptide (MG1) that binds to male gametes were identified. Importantly, when added
to a malaria infectious blood meal, each of these peptides blocked parasite fertilization,
suggesting that the peptides bound to a receptor and prevented its interaction with a ligand on
the gamete of the opposite sex. Our working hypothesis is that the peptide structurally mimics
the gamete ligand and that peptide and ligand compete for binding to the corresponding
receptor. This proposal lays out a research plan to identify the receptor to which the FG1 and
MG1 peptides bind and the ligands on the gametes of the opposite sex that the two peptides
structurally mimic. An additional aim is to characterize the proteome on the surface of female
gametes before and after fertilization, to gain insights on additional proteins involved in
fertilization and possible block to polyspermy.
Elucidation of mechanisms of fertilization is important not only for understanding the basic
biology of malaria and other parasitic diseases but could also lead to the identification of new
targets for blocking transmission and the spread of disease. Moreover, should the mechanisms
be conserved, our findings could be extended to the biology of fertilization of higher organisms.

## Key facts

- **NIH application ID:** 10064068
- **Project number:** 5R01AI127405-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MARCELO JACOBS-LORENA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2016-12-07 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064068

## Citation

> US National Institutes of Health, RePORTER application 10064068, Molecular mechanisms of Plasmodium fertilization (5R01AI127405-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064068. Licensed CC0.

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