# Single cell approaches to unravel transcriptional responses to drug pressure

> **NIH NIH P01** · UNIVERSITY OF NOTRE DAME · 2024 · $403,803

## Abstract

SUMMARY
The transcriptional response to drug exposure shapes the ability for a parasite to survive and grow during and
after treatment. During the prior grant period, we developed multiple tools to identify the drivers of drug
resistance. Single cell RNAseq of Plasmodium falciparum genetic crosses now enables rapid, robust
estimation of single cell expression quantitative trait loci (SCeQTLs) across the parasite life cycle. Pseudo Bulk
Segregant Analysis (pseudoBSA) now enables rapid linking of phenotypic variation to QTLs. We will use these
tools to capture the dynamic response of resistant and sensitive parasites to drug treatment. In Specific Aim 1,
we will define transcriptional networks associated with growth under drug exposure, and with rapid recovery
after treatment. We will identify which loci in the parasite genomes drive drug resistance and recovery using
pseudoBSA. We will identify SCeQTLs that link together drug response to growth and recovery. In concert with
Core B, we will identify high confidence polymorphisms that regulate the transcriptional response to drug
exposure and validate these with CRISPR/Cas9 gene editing. In Specific Aim 2, we will leverage this platform
to identify compensatory mutations relieving the impact of resistance mutations on parasite fitness and
understand their mechanism of action. This will involve novel genetic cross generation with Core A.

## Key facts

- **NIH application ID:** 10863153
- **Project number:** 2P01AI127338-06A1
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Ian Harry Cheeseman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,803
- **Award type:** 2
- **Project period:** 2017-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863153

## Citation

> US National Institutes of Health, RePORTER application 10863153, Single cell approaches to unravel transcriptional responses to drug pressure (2P01AI127338-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10863153. Licensed CC0.

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