# Mechanisms Governing Translational Regulation During Plasmodium Transmission

> **NIH NIH R56** · PENNSYLVANIA STATE UNIVERSITY, THE · 2022 · $477,453

## Abstract

Project Summary
New malarial infections start with a bite of a female Anopheles mosquito, which introduces the sporozoite form
of the Plasmodium parasite into the skin of that individual. To get to this point, the parasite must have
successfully infected and developed within the mosquito over the course of two weeks or more, using active
responses to overcome the mosquito’s defenses. Having accomplished this, the sporozoite must now switch
into a mode of preparation and become poised for a moment of opportunity to transmit from the mosquito back
to its mammalian host. In this proposed work, we will identify key mechanisms by which the sporozoite can
prepare itself through the translational regulation of selected mRNAs.
Recently, it was discovered that sporozoites use two overlapping and orthogonal programs of translational
repression (Programs 1 and 2) to allow translation of specific mRNAs to occur only at key moments in their
development. However, while we now know many specific mRNAs that are regulated by these programs, we
do not know what proteins act upon them to cause them to be silenced/repressed (trans factors). Moreover,
while we know when these programs are turned off during development and transmission of the parasite, we
do not know what environmental cues initiate this transition in translational regulation.
Therefore, in this proposed work we will investigate the protein trans factors that allow for selective regulation
of mRNAs that are known to be critical to sporozoite development and transmission. Through this work, we will
identify the consequences of interfering with these regulatory programs, the environmental stimuli that are
sensed to trigger the release of translational repression, and the central role that the specialized ribosome
plays in these processes. These experimental questions will be addressed through reverse genetics, protein
biochemistry, imaging flow cytometry, transcriptomics, proteomics, and cryogenic electron microscopy (cryo
EM). In accomplishing this, we aim to identify crucial regulatory features of the malaria parasite that control
sporozoite development and transmission to a new mammalian host.

## Key facts

- **NIH application ID:** 10667735
- **Project number:** 2R56AI123341-06A1
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** Scott E Lindner
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $477,453
- **Award type:** 2
- **Project period:** 2016-11-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667735

## Citation

> US National Institutes of Health, RePORTER application 10667735, Mechanisms Governing Translational Regulation During Plasmodium Transmission (2R56AI123341-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10667735. Licensed CC0.

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