# Characterizing sexual development of the human parasite Schistosoma mansoni

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $589,087

## Abstract

Schistosomiasis is a neglected tropical disease caused by parasitic flatworms, called schistosomes,
that affects hundreds of millions of the world’s poorest people. The pathology of this disease stems
from the fact that schistosomes can lay hundreds-to-thousands of eggs per day while living in the
blood vessels of their human hosts. Therefore, understanding the mechanisms that control
schistosome egg production could present new opportunities to both limit the spread of the disease
and abrogate the pathology caused by the parasite. Interestingly, female schistosomes only become
sexually mature when they are in constant physical contact with a male worm. Indeed, females
grown in the absence of male worms produce no eggs and cause no serious adverse consequences
in their hosts. Although the requirement of male worms for female sexual development was
described almost 100 years ago, there are few insights into how this process is regulated on a
molecular level. A major impediment for addressing this issue is that current culture conditions do not
support schistosome sexual development in vitro. To address this issue we have developed a novel
media formulation that supports male-induced female sexual development and long-term egg
production in vitro. Capitalizing on this medium, we have made two important observations. First, we
find that gene expression changes in females immediately upon pairing with a male worm do not
occur in the reproductive organs, but rather in the parasite’s somatic tissues including neurons and
muscle cells. Second, we identified a transcription factor highly expressed in the nervous system and
muscle cells that is essential for female sexual development after pairing with a male worm. Based
on these data, we hypothesize that somatic non-reproductive cell types in the female worm are
responsible for perceiving the presence of the male worm and in turn regulating the development of
the reproductive organs. Defining the cell types directly responsible for perceiving the presence of
the male worm could provide important clues about the nature of the male-derived signal that controls
female sexual development. Therefore, we will test our central hypothesis in two specific aims. In
Specific Aim 1 we will describe the cellular and molecular response of the reproductive and somatic
tissues of the female worm to pairing with a male worm using basic developmental biology
approaches and single cell RNA sequencing. Specific Aim 2 will utilize RNA interference and single
cell RNA sequencing to discover genes and somatic cell types that are essential for controlling female
maturation and determine how these genes act in concert to coordinate the female response to
pairing with a male. We expect these studies to define the signaling events that stimulate female
maturation and hope they will suggest new therapeutic targets against schistosomes.

## Key facts

- **NIH application ID:** 10207379
- **Project number:** 5R01AI150776-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** James J Collins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $589,087
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207379

## Citation

> US National Institutes of Health, RePORTER application 10207379, Characterizing sexual development of the human parasite Schistosoma mansoni (5R01AI150776-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10207379. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*