# Structural basis of the polar tube invasion machinery from microsporidia parasites

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $648,532

## Abstract

Project Summary/Abstract
 Microsporidia are unicellular, ​fungal​ parasites with a wide host-range, from insects to humans. ​They are
emerging pathogens, classified as NIAID Category B opportunistic pathogens, and cause microsporidiosis in
immunocompromised patients.​ To gain entry into a target cell, microsporidia employ a remarkably unique and
specialized harpoon-like invasion machinery called the polar tube, which is conserved among microsporidial
species. While initially coiled neatly within the spore of the parasite, infection of a new cell begins with the rapid
extrusion of the polar tube from the spore on a fast timescale (< 2s), which anchors the spore to the host cell.
After it has been fired, the polar tube is thought to act as a conduit for the transfer of the infectious
“sporoplasm” into the target cell, where replication can begin. Early work has yielded global insights into this
process, and the molecular and structural underpinnings of the invasion process are ripe for exploration with
modern techniques, such as cryo electron microscopy. This work aims to address fundamental questions and
paradoxes in our understanding of the microsporidial polar tube machinery and how it drives invasion into host
cells. We will use a combined bottom-up (structural biology, biochemistry and other ​in vitro​ techniques on
purified proteins) and top-down (​in vivo​ light microscopy, electron tomography) approach; the intersection of
these approaches will allow us to unravel the mechanistic biology of this unique invasion process. ​Here we
focus on three human pathogens: ​Anncaliia algerae, Encephalitozoon cuniculi​ and ​Encephalitozoon hellem​.
 The specific aims are 1) To characterize the dynamics of polar tube firing and movement of sporoplasm
through the tube using high-speed optical microscopy, and to comprehensively define the composition of the
polar tube​ using mass spectrometry; 2) To biochemically and structurally characterize the individual protein
components of the polar tube organelle using X-ray crystallography, single particle cryo electron microscopy
and protein-protein interaction assays; 3) To elucidate the overall architecture and packing of the polar tube in
the spore using structural cell biology techniques such as serial block face scanning electron microscopy
(SBFSEM) and cryo focused ion beam scanning electron microscopy (cryo FIB-SEM) followed by cryo electron
tomography (cryo ET).

## Key facts

- **NIH application ID:** 9913209
- **Project number:** 1R01AI147131-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Gira Bhabha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $648,532
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913209

## Citation

> US National Institutes of Health, RePORTER application 9913209, Structural basis of the polar tube invasion machinery from microsporidia parasites (1R01AI147131-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9913209. Licensed CC0.

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