# Control of parasite invasion by a microneme protein complex conserved in Apicomplexans

> **NIH NIH R01** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2022 · $487,500

## Abstract

7. PROJECT SUMMARY/ABSTRACT
Apicomplexan parasites include the etiologic agents of many widespread infections of humans and livestock,
such as malaria and toxoplasmosis. These diseases are caused by destruction of the host tissues in which the
parasites replicate. Because apicomplexans only replicate inside host cells, the process of invasion is critical to
their survival and pathogenesis. Invasion is mediated by the release of proteins from specialized secretory
organelles at the apical end of the parasite, the micronemes and rhoptries. Microneme proteins include
adhesins that support parasite motility and are therefore secreted as soon as parasites emerge from replication
and start migrating towards new host cells to infect. Rhoptries, by contrast, secrete their contents only upon
host cell recognition once parasites have committed to invasion. Evidence suggests that the release of rhoptry
contents depends on the prior secretion of microneme proteins; however, the molecular events that link these
two processes are unknown. Based on a genome-wide screen in the model apicomplexan Toxoplasma gondii,
our lab recently identified a conserved microneme protein necessary for invasion of human cells, which we
named CLAMP. Our preliminary studies show that CLAMP is necessary for rhoptry secretion and stably
associates with two microneme proteins: SPATR, which was previously implicated in invasion, and an
uncharacterized protein we call CLIP. We hypothesize that these interactions represent a novel invasion
complex necessary for rhoptry protein secretion. Our first aim is to compare the functions of CLAMP,
SPATR, and CLIP; investigate how they oligomerize; and elucidate the relationship between complex
formation and rhoptry secretion. In our second aim, we will identify and characterize host and parasite proteins
that interact with the CLAMP invasion complex. Finally, our third aim will take an unbiased look at the host cell
factors that stimulate rhoptry protein secretion, which may intersect with the CLAMP complex to regulate this
key step in apicomplexan invasion. Based on the conservation of the parasite proteins involved, we expect that
the principles uncovered will be generalizable to the phylum and broadly inform our understanding of these
infectious agents.

## Key facts

- **NIH application ID:** 10302285
- **Project number:** 5R01AI144369-03
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **Principal Investigator:** Sebastian Lourido
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $487,500
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302285

## Citation

> US National Institutes of Health, RePORTER application 10302285, Control of parasite invasion by a microneme protein complex conserved in Apicomplexans (5R01AI144369-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10302285. Licensed CC0.

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