# Variant surface glycoprotein diversification in Trypanosoma brucei

> **NIH NIH DP5** · JOHNS HOPKINS UNIVERSITY · 2020 · $405,000

## Abstract

PROJECT SUMMARY
Trypanosoma brucei is a causative agent of both human and animal African trypanosomiasis, devastating
diseases affecting sub-Saharan Africa. A dense variant surface glycoprotein (VSG) coat covers this
extracellular parasite and effectively masks all other antigens on the cell surface. T. brucei evades elimination
by the mammalian host's immune system through antigenic variation of its VSG coat: it “switches” the
expressed VSG, taking advantage of a genomic repertoire of ~2000 VSG-encoding genes. However, parasite
populations in vivo express a diverse set of VSG-encoding genes. The number of expressed VSGs over 30
days of infection can approach one-third of the functional VSG repertoire within the parasite genome, which
highlights an interesting question: if the existing genomic repertoire can be used up in a matter of months, how
can an infection be sustained for years in the field? The goal of this application is to investigate the
mechanisms by which T. brucei diversifies its genomic VSG repertoire in order to sustain infection. Preliminary
data suggest that extravascular spaces may provide an important area for T. brucei to diversify its VSG archive
in the absence of immune pressure. In the first aim of this proposal, the role of this extravascular niche in VSG
diversification will be investigated. The second aim will take advantage of CRISPR/Cas9 technology combined
with a novel high-throughput sequencing method to investigate the segmental gene conversion events
resulting in novel “mosaic” VSGs. In the third aim, the mutation of individual VSGs will be studied, in order to
understand the mechanisms that govern the evolution of the VSG archive within the parasite genome over the
course of infection. These studies will begin to elucidate the mechanisms by which T. brucei sustains a long-
term infection in its host, which will be important for the development of new strategies for treatment of this
neglected tropical disease. Three aims are proposed to accomplish these goals: 1) To elucidate the role of
extravascular spaces in VSG diversification; 2) To identify the mechanisms responsible for the segmental gene
conversion events that generate mosaic VSGs; 3) To quantify the rate of hypermutation of VSGs.

## Key facts

- **NIH application ID:** 9989923
- **Project number:** 5DP5OD023065-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Monica Mugnier
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989923

## Citation

> US National Institutes of Health, RePORTER application 9989923, Variant surface glycoprotein diversification in Trypanosoma brucei (5DP5OD023065-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989923. Licensed CC0.

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