# Defining and Exploiting the Circadian Clocks in Malaria Parasites

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $1,399,125

## Abstract

Project Summary | Abstract
Malaria’s immense public health burden is undisputable with numbers of deaths increasing since 2020, however
the mechanism for its characteristic rhythmic fevers remains poorly understood. Earth rotation has been a
driving force for organisms to evolve circadian clocks to anticipate daily rhythms. In humans, circadian clocks
regulate multiple physiological aspects of biology, including sleep-wake cycles, metabolism, and immune
defense. Human’s circadian biology leads to body rhythms experienced by the pathogens that infect us. Malaria,
a parasitic disease that kills over half a million people each year, is famous for its periodic fevers. Malarial
periodic fevers are a consequence of the synchronous bursting of the host’s red blood cells, containing parasites
and metabolic waste. It has long been assumed that malarial periodic fevers and the parasite replication rhythms
that cause them were driven by the host’s own circadian rhythms. The existence and role of the malarial
parasites’ intrinsic clocks has been unknown. Recent discoveries showed that malaria parasite rhythms are
intrinsic. Parasite’s synchronous bursting persists even when infecting a circadian clock mutant arrhythmic host.
However, the molecular regulation and functions of malaria clock remains elusive. This led to the hypothesis
that the parasite clock is an essential component of parasite biology and a contributor to pathogenesis of
parasitic diseases. The overall aim of this proposal is to decode the molecular processes that regulate circadian
rhythms in parasites and discover how disrupting their regulatory networks impacts the pathogenesis of malaria
and transmission. By using forward-genetics screens, behavioral, molecular and bioinformatic approaches, the
molecular machinery of malaria parasites will be identified. This is an emerging new field of research of
circadian rhythms in infectious diseases. The fact that multiple parasitic infections show daily rhythms further
supports the hypothesis that circadian rhythm in parasites is essential for their biology, fitness and potentially
transmission - and that deregulation of this biological rhythm may disrupt their well-orchestrated success in
causing infections. This proposal will provide a foundation for discovering parasite clocks in other parasitic
diseases such as toxoplasmosis and leishmaniasis. Beyond the significance of this work to basic parasitology
discovery, it could also unravel insights on the disease pathogenesis by uncovering the mechanism for malaria’s
main fever symptom. Parasitic diseases pose increasing threats to global public health and this innovative
research will provide new targets to directly disrupt the rhythms that contribute to the disease.

## Key facts

- **NIH application ID:** 10687634
- **Project number:** 1DP2GM154010-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Filipa Rijo-Ferreira
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,399,125
- **Award type:** 1
- **Project period:** 2023-09-25 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687634

## Citation

> US National Institutes of Health, RePORTER application 10687634, Defining and Exploiting the Circadian Clocks in Malaria Parasites (1DP2GM154010-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10687634. Licensed CC0.

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