# Mechanism of Infectivity Acquisition in African Trypanosomes

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $458,986

## Abstract

Project Summary
 Unraveling the biology of human pathogens is fundamental toward understanding mechanisms of
pathogenesis and identifying genes essential for survival in the host. This application focuses on the
protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals in
sub-Saharan Africa. There are no vaccines, and therapeutic drugs have serious side effects and
decreasing efficacy. Thus, there is a pressing need for research to better understand the biology of these
human pathogens and the mechanisms they use to survive within their hosts. T. brucei undergoes a
complex life cycle between the mammalian host and the blood-feeding tsetse fly vector, which among
others involves changes in cell morphology, surface coat composition, metabolism, signaling pathways
and gene expression. Consequently, these parasites have evolved adaptations to allow for their survival
in both the gut and salivary glands of the tsetse fly, as well as in the bloodstream of their mammalian
host. By overexpressing a single RNA-binding protein (RBP6) in non-infectious trypanosomes, we
recapitulated in vitro the events leading to acquisition of infectivity in the insect vector, including the
expression of metacyclic variant surface glycoproteins (mVSGs). The overall goal of the proposed work
here is to identify the mechanism by which RBP6 activates developmental progression to infectious
metacyclics and to characterize the RNA binding protein network that regulates the developmental
program leading to epimastigotes and infectious metacyclics. To accomplish these goals, we will build on
our major findings in the previous funding period, namely the identification of initial targets of RBP6
function, the depiction of the molecular characteristics of metacyclics, and the identification of a large
compendium of molecules linked to the developmental program leading to infective metacyclic parasites.
We will use innovative approaches involving a screen for RBP6 function with deep mutational scanning
by combining metacyclic selection and high-throughput DNA sequencing and analyze gene expression at
the single cell level with RNA-Seq. Taken together our research plan provides unique opportunities to
illuminate the developmental program leading from non-infective procyclics to infectious metacyclics, a
crucial process in the T. brucei life cycle.

## Key facts

- **NIH application ID:** 9870867
- **Project number:** 5R01AI110325-07
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** CHRISTIAN TSCHUDI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $458,986
- **Award type:** 5
- **Project period:** 2014-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870867

## Citation

> US National Institutes of Health, RePORTER application 9870867, Mechanism of Infectivity Acquisition in African Trypanosomes (5R01AI110325-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870867. Licensed CC0.

---

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