# Role of Translesional Polymerases in Genome Diversification of the Malaria Parasite

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $585,839

## Abstract

Project Summary/Abstract:
Malaria continues to be a major cause of morbidity and mortality among people living in the tropical and
subtropical regions of the world. The ability of parasites to continuously generate sequence diversity
within their genomes is a major contributor to the inability to develop effective erythrocytic stage
vaccines and to the ever-present problem of drug resistance. Yet, key gaps remain in our
understanding of how the parasite genome is maintained. Our long-term goal is to identify pathways
that are crucial to maintaining the parasite genome and understand how these repair pathways impact
mutability and genome plasticity.
Translesion (TLS) polymerases are specialized DNA polymerases that are capable of continuing DNA
synthesis through damage bases and difficult templates, though they accomplish this in an error prone
manner. In model systems, TLS polymerases generate the majority of novel mutations. There are only
two TLS polymerase present in the primate malaria genomes, Rev 1 and pol ζ. Our hypothesis is that
these polymerases play a crucial role in parasite genome maintenance and contribute to persistence of
and pathogenesis of malaria by a) driving the generation of antigenic diversity by promoting
homologous recombination (HR) between semi-homologous but non-identical members of multicopy
gene families and b) contributing to the generation of sequence variation throughout the genome and in
turn to the development of drug resistance. Using genome editing techniques, mutagenesis and SMRT
sequencing techniques, we seek to uncover the role of TLS polymerases in the human malaria
parasite, Plasmodium falciparum.
Our proposed research will uncover unique aspects of Plasmodium DNA repair that will be important for
understanding malaria and to those that study genome maintenance in general. Our aims are designed
to have direct impact on the important clinical aspects of malaria, the parasite's propensity to develop
drug resistance and evade the host immune system. This study addresses an important and neglected
aspect of parasite biology.

## Key facts

- **NIH application ID:** 10399466
- **Project number:** 5R01AI146153-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Laura Kirkman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $585,839
- **Award type:** 5
- **Project period:** 2019-06-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399466

## Citation

> US National Institutes of Health, RePORTER application 10399466, Role of Translesional Polymerases in Genome Diversification of the Malaria Parasite (5R01AI146153-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399466. Licensed CC0.

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