# Fatty Acid Synthesis, Surface Molecules, and Immune Evasion

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2020 · $220,266

## Abstract

SUMMARY
African sleeping sickness is so deadly because the causative agent, Trypanosoma brucei, has a powerful array
of defenses against the immune system. Because these defenses so effectively neutralize the immune system,
drugs to treat sleeping sickness must kill nearly all the parasites to be curative, and vaccine development has
been extremely difficult. The 5 approved treatments are lengthy and involve high doses, leading to toxic side
effects and a need for significant medical infrastructure. New drugs for sleeping sickness are desperately
needed, yet there are only 2 in clinical trials. The long-term goal is to understand the role of lipid metabolism in
host adaptation and immune evasion, and to use this knowledge to pursue improved treatments for African
sleeping sickness. The objective of this proposal is to define how fatty acid synthesis is linked to the function of
the parasite's Variant Surface Glycoprotein (VSG), a lipid anchored protein that mediates all the major immune
evasion mechanisms. The central hypothesis is that ongoing fatty acid synthesis is required for VSG to
function in immune evasion. Our central hypothesis will be tested with two Specific Aims: (1) Examine
dependence of VSG trafficking and recycling on fatty acid synthesis and (2) Examine dependence of VSG
switching upon fatty acid synthesis. The general approach is to block fatty acid synthesis and assess the effect
these changes have upon VSG function. The proposed research is innovative in its exploration of a novel
linkage between fatty acid synthesis and immune evasion and in the provision of new reagents and tools to
study antigenic variation. The proposed work is significant because it provides new understanding about the
ability of T. brucei to evade the immune system, one of the major challenges to both vaccine development and
to developing safe, effective treatments. The proposed work will have a positive benefit to human health by
providing proof-of-concept that it is possible to target the parasite's immune evasion mechanisms, which could
open up new directions in the development of safer, more effective treatments for sleeping sickness and
positively affect efforts in vaccine development.

## Key facts

- **NIH application ID:** 9900824
- **Project number:** 5P20GM109094-05
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Kimberly Sue Paul
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,266
- **Award type:** 5
- **Project period:** — → 2022-07-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900824

## Citation

> US National Institutes of Health, RePORTER application 9900824, Fatty Acid Synthesis, Surface Molecules, and Immune Evasion (5P20GM109094-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900824. Licensed CC0.

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