# Glycosome specialization in African trypanosomes

> **NIH NIH R56** · CLEMSON UNIVERSITY · 2020 · $369,072

## Abstract

ABSTRACT
 Kinetoplastids have essential organelles called glycosomes that compartmentalize biochemical
pathways. Our ability to target glycosomes for therapeutic development is hindered by a limited understanding
of the processes that regulate these organelles. Glycosomes are heterogeneous; however, the biological
significance of this organelle diversity and the molecular mechanisms that regulate it are unknown. We
hypothesize that glycosome specialization is a consequence of functional specialization and organelle
maturation; processes that require proteins called peroxins (Pexs). To test our hypothesis, we will pursue the
following aims. Aim 1: Resolve the contribution of functional specialization to glycosome heterogeneity.
Leveraging our recent development of a highly sensitive flow cytometry-based platform we will define the
molecular composition of glycosomes (functional specialization) by organelle sorting, mass spectrometry,
superresolution microscopy and electron microscopy. Aim 2: Identify the contribution of glycosome biogenesis
to organelle heterogeneity. Based on the peroxisome paradigm, we propose that the formation of preglycosomal
vesicles at the ER, maturation, and proliferation of glycosomes, which involve multiple classes of preperoxisomal
intermediates, can contribute to heterogeneity. We will define the preglycosomal vesicle populations in parasites
using flow cytometry. During peroxisome biogenesis in yeast, Pex13 traffics through the ER via the Sec61
translocation channel. Signal recognition particle (SRP), which targets secretory proteins to the Sec61 channel
binds Pex13.1 (one of two Pex13s in T. brucei; see below). We will determine how glycosome number,
morphology, size and parasite viability is affected in SRP-deficient cells. Aim 3: Define the composition of
glycosome protein import complexes of T. brucei. Functional specialization requires the selective import of
proteins belonging to a particular pathway or process. We will define the protein composition and post-
translational modifications of glycosome import complexes and determine how phosphorylation influences import
complex assembly, glycosome biogenesis, and glycosome protein import. Upon completing this first of its kind
systematic analysis of glycosome specialization, we will know the extent to which glycosomes become
functionally specialized and will have made inroads into resolving the de novo pathway of glycosome formation
in trypanosomes. Additionally, we will have defined the molecular machinery that regulates glycosome
biogenesis and functional specialization. Small molecules that inhibit protein:protein interactions that mediate
glycosome protein import are lethal to parasites. We anticipate that this work will reveal additional protein
interactions that can be exploited for pragmatic gain and will reveal novel mechanisms that govern organelle
biogenesis and specialization in eukaryotes. The flow cytometry methods developed here can be expanded to
th...

## Key facts

- **NIH application ID:** 10239736
- **Project number:** 1R56AI143687-01A1
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** MEREDITH T MORRIS
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,072
- **Award type:** 1
- **Project period:** 2020-09-03 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239736

## Citation

> US National Institutes of Health, RePORTER application 10239736, Glycosome specialization in African trypanosomes (1R56AI143687-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10239736. Licensed CC0.

---

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