# Mechanisms of protein production in the parasite Giardia Iamblia

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2020 · $231,238

## Abstract

SUMMARY
Giardia lamblia is a unicellular protist whose parasitic infections of humans is a significant threat to health
worldwide. Treatments are limited and of variable efficacy: in the developing world Giardia infection can lead
to severe disease and death, while in the developed world outbreaks have occurred even from treated water
sources. Although the basic molecular biology in Giardia is similar to that in traditional model systems, it is
also a deeply branching eukaryote, and so many aspects of its gene regulatory mechanisms have diverged
substantially. The fundamental molecular differences between Giardia and its hosts present an opportunity
for therapeutic intervention. However, little is understood about these differences, and thus this treatment
opportunity has not yet been exploited. In particular, many aspects of how Giardia initiates protein
production seem different from what has been studied in traditional model systems, but, currently, the
mechanistic implications of these differences remains mysterious. Giardia mRNAs have remarkably short
untranslated regions, their ribosomes do not appear to scan, and our analysis suggests that they lack some
of the core initiation factors shared almost universally in eukaryotes. These results suggest fundamental
differences in the mechanism of initiation, which we will explore through a biochemical and structural
approach. We propose to partially address this gap through an initial exploration of fundamental features of
the protein synthesis machinery of Giardia. We will take advantage of our ability to culture and genetically
manipulate Giardia, combined with our expertise in mechanistic studies of translation initiation and structural
biology. We will pursue two aims: (1) We will solve the structure of the Giardia ribosome and its
subunits using cryo-electron microscopy. Preliminary analysis shows unexpected differences in these
ribosomes compared to other eukaryotes; observing the conformational implications of these differences will
provide an essential foundation for detailed mechanistic studies and could suggest therapeutic targets. (2)
We will investigate the composition and architecture of Giardia translation initiation complexes.
Overall, these exploratory studies promise to yield discoveries related to the basic molecular machinery
used by Giardia to generate protein, laying the foundation for future studies that will more broadly and
deeply interrogate gene regulation mechanisms in Giardia.

## Key facts

- **NIH application ID:** 9874922
- **Project number:** 1R21AI149210-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Olivia Selfridge Rissland
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,238
- **Award type:** 1
- **Project period:** 2020-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874922

## Citation

> US National Institutes of Health, RePORTER application 9874922, Mechanisms of protein production in the parasite Giardia Iamblia (1R21AI149210-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874922. Licensed CC0.

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