# Elucidating the Mechanistic Basis for Phagotrophy in the Protozoan Trypansoma cruzi

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2023 · $302,000

## Abstract

PROJECT SUMMARY
Whether its photons or fries eating is fundamental for life. From this basic principle, living organisms have
evolved innumerable strategies to capture energy and nutrients from their environment, leading, in turn, to the
incredible ecological diversity spanning the gamut from light eating photosynthetic autotrophs to predatory
heterotrophs. As part of the world’s aquatic ecosystems, the expansive family of heterotrophic protozoan
predators play a critical role in environmental carbon and nutrient cycling as they consume 75% of primary
producing planktonic autotrophs daily. The vast majority of these flagellated phagotrophs use self-generated
currents to funnel their prokaryotic prey into an ancient and highly enigmatic feeding apparatus prior to
digestion. This feeding structure begins as a plasma membrane surface opening (cytostome), descends into
an internal tubular invagination (cytopharynx) and ends with prey being enveloped within budding vesicles
destined for lysosome fusion. Here we refer to this organelle as the cytostome/cytopharynx complex or SPC
and, despite its near ubiquitous presence in protozoans, next to nothing is known mechanistically about how
this structure is formed or functions. Intriguingly, a class of these phagotrophic predators known as the
kinetoplastids, gave rise to a lineage of parasitic protozoa that can infect a wide variety of organisms ranging
from plants to humans. Curiously, one species in particular, Trypanosoma cruzi, retained this ancestral
organelle much like its free-living relatives (e.g. bodonids) and continues to use it as its primary route of
endocytosis. Due to the fact that T. cruzi is easily culturable, genetically tractable and not reliant on SPC
mediated endocytosis for viability in vitro, we have been able to conduct the first ever in-dept molecular
analyses of this ubiquitous feeding organelle. Our initial published work on this structure described the first
known proteins targeted to the SPC and was followed by a report on the identification of a family of SPC
targeted myosin motors that we show contribute directly to the endocytic process. As a continuation of these
studies, this proposal seeks to generate a holistic understanding of how SPC mediated endocytosis
fundamentally functions. We will begin by dismantling the unified activity of endocytosis into its constituent
processes; cargo capture through surface receptors (Aim1), receptor signal transduction and activation of
endocytic machinery (Aim2) and finally active transport of phagocytosed cargo along the SPC for digestion
(Aim3). Each of these aims will address important basic aspects of protozoan biology that continue to remain
poorly understood. Critically, this proposal will combine both a broad approach to identify cytostomal surface
receptors and SPC specific signaling components with a focused analysis of the role of the Act2 isoform in the
endocytic process. By combining this model organism with a broad range of ...

## Key facts

- **NIH application ID:** 10630908
- **Project number:** 5R01GM144545-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** RONALD DREW ETHERIDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $302,000
- **Award type:** 5
- **Project period:** 2022-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630908

## Citation

> US National Institutes of Health, RePORTER application 10630908, Elucidating the Mechanistic Basis for Phagotrophy in the Protozoan Trypansoma cruzi (5R01GM144545-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10630908. Licensed CC0.

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