# Mechanisms of Virulence in Malaria Parasites

> **NIH NIH SC3** · SAN FRANCISCO STATE UNIVERSITY · 2020 · $116,250

## Abstract

PROJECT SUMMARY/ABSTRACT
A major problem in the field of eukaryotic infectious diseases remains unsolved: why are some parasites
pathogenic but other closely related ones relatively benign? Here we propose to address this problem by
studying malaria, a diverse suite of pathogens where some cause severe morbidity yet others can be
asymptomatic. By studying the gene expression of malaria parasites that infect birds, we will elucidate the
evolution of pathogenicity and identify genes that cause morbidity. We will test the hypothesis that certain
genes are differentially expressed between virulent and benign pathogens. Using a bioinformatics approach,
we will compare the transcriptomes of avian pathogens and identify whether different genes are expressed,
and/or if they are expressed at different levels between the virulent and non-virulent Plasmodium species. By
selectively mutating avian malaria genes, we will verify the alleles responsible for pathogenesis. The
CRISPR/Cas9 approach has been used recently to disrupt genes in Plasmodium falciparum. This will be the
first use of this approach in a non-mammalian malaria system. The proposed research is timely and significant
in that it will advance the field of malaria research by providing an important new model system to identify
factors contributing to malaria pathogenicity. This work is innovative because birds provide the only model
system where two highly related malaria parasites cause such fundamentally different outcomes to both
laboratory and naturally occurring wild hosts. The long-term and cross-disciplinary goal of this research agenda
is to elucidate the evolution of pathogenicity and identify conserved virulence mechanisms that may be
overlooked using mammalian model systems.
The aims of the proposal are to:
1. Sequence the complete transcriptomes of select avian malaria parasites. 2. Characterize differences in
gene expression between virulent and non-virulent parasite strains. 3. Use a CRISPR/Cas9 approach to
disrupt virulence genes and confirm effects through the infection of laboratory birds.
The project will support the education of future scientists through an integrative approach to research and
education. It will train students in cutting edge technologies associated with infectious disease research, and
provide valuable experiences for graduate and undergraduate students at an urban university serving large
numbers of underrepresented minority students. The developmental objectives of the PI will be met by working
with outstanding collaborators, which will further his training in the genomics of malaria.

## Key facts

- **NIH application ID:** 9876956
- **Project number:** 5SC3GM118210-04
- **Recipient organization:** SAN FRANCISCO STATE UNIVERSITY
- **Principal Investigator:** Ravinder Nath Marius Sehgal
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $116,250
- **Award type:** 5
- **Project period:** 2017-05-20 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876956

## Citation

> US National Institutes of Health, RePORTER application 9876956, Mechanisms of Virulence in Malaria Parasites (5SC3GM118210-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9876956. Licensed CC0.

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