Stopping the Clock

The United States eliminated malaria in the early 1950—although in 2023, the U.S. marked its first locally acquired case since then—but for much of the world the mosquito-borne disease is a major threat. In 2023, malaria killed nearly 600,000 people—mostly children under five—in sub-Saharan Africa. Nearly 290 million people are infected with malaria each year.

The disease is caused by the Plasmodium parasite that infects the female Anopheles mosquito. The mosquito gets the disease by biting a person infected with the parasite—and then ingesting their blood. The mosquito then spreads the disease by biting another person or animal (animals can contract malaria, too).

There are treatments to lessen the disease’s destruction of red blood cells, which brings fevers, chills, and life-threatening conditions like organ failure and severe anemia, but the parasite-infected mosquitoes are developing resistance to the pesticides that can control them and the parasites themselves are evolving to resist medicines used to kill them. The efficacy of available vaccines is very low, and delivering them to the rural areas where they are most needed is a logistical nightmare.

But in Filipa Rijo-Ferreira’s lab at UC Berkeley School of Public Health, researchers are uncovering new ways to understand how malaria parasites and their mosquito carriers keep track of time—with an eye toward developing more effective disease interventions. They also study other parasitic diseases, such as sleeping sickness, a parasitic infection transmitted by the bite of infected tsetse flies, and toxoplasmosis.

“One of the major symptoms of the malaria disease is its periodic fevers that happen at very specific times of day, always in multiples of 24 hours—like a circadian clock,” said Rijo-Ferreira, who joined the school of public health faculty as an assistant professor in Infectious Diseases and Vaccinology in 2022.

Circadian rhythms—or the circadian clock—are the patterns that the body follows based on a 24-hour day. As the Cleveland Clinic puts it, “This rhythm tells your body when to sleep and when to wake up. It also affects several other body processes, like your hormones, digestion and body temperature. It’s like you have a tiny conductor inside your body, orchestrating a 24-hour symphony of biological processes. Your body sets your circadian rhythm naturally, guided by your brain. But outside factors, like light, can affect the rhythm, too.”

Circadian clocks module half of our genes to be expressed once a day. Genetic mutations of the clock or disruptions by shiftwork lead to higher rates of cancer and metabolic dysfunction.

“First, we were trying to find out if parasites, which cause devastating diseases, have a way to tell time—if a parasite has a clock. We now know that parasites have clocks, but we have no idea how these clocks work,” said Rijo-Ferreira. That mystery led to a fruitful new avenue of research for her lab.

One thing the UC Berkeley researchers have discovered is that these internal clocks are very important for the transmission of malaria. At certain times of the day, the malaria parasite is more infectious to its mammalian host than other times. Why, they don’t yet know.

Her team’s landmark paper, published in March 2025 in Nature Microbiology, revealed how malaria parasites and mosquito vectors synchronize their biological clocks to enhance transmission efficiency.

The research showed that the mosquito’s salivary glands, where parasites are harbored, are under strong circadian control, with half of their genes cycling daily. These genes—particularly those tied to blood-feeding—peak just before sunset, anticipating mosquito biting time and priming transmission.

“We were struck by how tightly the mosquito’s biology is tuned to time of day,” said Rijo-Ferriera, who is also an assistant professor of molecular cell biology and an Investigator at the Chan Zuckerberg Biohub. “Our research suggests that host, mosquito, and parasite clocks have coevolved to maximize transmission potential. If we can interrupt that alignment, we may be able to reduce the likelihood of infection.”

Beyond malaria, Rijo-Ferriera is also studying how to optimize treatment and prevention of other diseases by circadian medicine. Her lab has also shown that the sleeping sickness clock controls the metabolism of the parasite, regulating its ability to create energy. In addition, because many anti-parasitic drugs act on metabolic pathways, the researchers tested and found that the clock makes sleeping sickness parasites more susceptible to suramin, a drug commonly used in the clinic, at specific times of the day.

Rijo-Ferreira has already received national recognition for her work, which combines molecular parasitology, mosquito development and immunology, and neuroscience.

She was selected as a 2025 Freeman Hrabowski Scholar, a prestigious honor, including lab funding, an award awarded to outstanding early career faculty by the Howard Hughes Medical Institute.

In 2023, Rijo-Ferreira was awarded $1.5 million “Director’s New Innovator Award,” by the National Institutes of Health (NIH) for her “high-risk, high-reward” research on circadian rhythms and parasitic infections. The award supports exceptionally creative, early-career investigators who propose innovative, high-impact projects. At the same time, she also received a $300,000 grant under the NIH Searle Scholars Program, which supports “independent research of exceptional young faculty in the biomedical sciences and chemistry.”

Earlier, in 2022, Rijo-Ferreira was named a “Wunderkind” by STAT, the online health and medicine publication published by Boston Globe Media.

“Filipa is intrepid and brave,” said Dr. Joseph S. Takahashi, chair of the Department of Neuroscience at University of Texas Southwestern Medical Center, in whose lab Rijo-Ferreira did her postdoctoral work, as part of a collaboration with Dr. Luisa Figueiredo, a parasitologist in her native Portugal.

“She’s really known for showing that parasites, such as the parasite that causes sleeping sickness and the parasites that cause malaria, have their own internal 24-hour clock,” Takahashi said. “It was surprising to much of the parasite field, because they didn’t really expect the parasite to be that sophisticated. It gives us a new target for drug development.”

“If her lab can determine how the parasites’ internal clocks work”, he said, “there will be a strong chance of interrupting its cycles.”

“If we can interrupt that alignment, we may be able to reduce the likelihood of infection”

On any given day, the Rijo-Ferreira Lab is buzzing with mosquitos in tanks. Her lab team, which currently includes 14 researchers, among them undergraduates and postdoctoral fellows.

Some are trained to study parasites; others are electrical engineers, computational biologists, and circadian rhythm specialists, like herself. Much of the work goes into generating tools that can be used for their studies. The lab itself is a prime example of interdisciplinary research. The team uses technical approaches spanning from next-generation sequencing, to cellular and behavioral assays to investigate the interactions of these parasites with their hosts.

“We have to be creative and develop tools,” Rijo-Ferreira said. “That’s why it’s been really important to have people who have all different angles of training and interests.”

The goal is using the team’s discoveries to fight parasites by disrupting their clocks, disrupting the clocks of the mosquito carrying the parasite, or treating the patient directly.

A career spanning two continents

Rijo-Ferriera was born in a small town outside of Lisbon. As a child, she often brought home plants and bugs to examine under a toy microscope. After high school, she received her bachelor’s degree in molecular and cellular biology from Nova University of Lisbon.

While earning her master of science degree, she joined the laboratory of Dr. Charles Bangham at Imperial College London, where she studied immunology and infection. From there Rijo-Ferreira returned to Portugal, where she began work on her doctorate at University of Porto. In Porto, she became fascinated with molecular parasitology and circadian rhythms, combining these two fields for her research. She eventually joined the research team of well-known parasitologist Dr. Luísa Figueirdo.

From there, she connected with Takahashi at the University of Texas Southwestern Medical Center. Her work on circadian rhythms in the human parasites Trypanosoma Brucei (the sleeping sickness parasite) and Plasmodium (which causes malaria) won the university’s Brown-Goldstein Award for Excellence in Postdoctoral Research, the highest honor the School of Biomedical Sciences bestows.

Dr. Victoria Acosta-Rodriguez, chief of the circadian biology of aging unit at NIH’s National Institute of Aging, called Rijo-Ferreira an outstanding scientist, with a gift for communication.

“She’s such a good communicator that everything sounds easy coming out of her mouth,” Dr. Acosta-Rodriguez said. “Circadian rhythms have such a huge impact in our life, you know, day-to-day life, and it has been a bit underappreciated.”

“At first we thought that the parasites were just followers, when they were in the mosquito, they would follow whatever the mosquito’s rhythms were. And when they were in the humans, they would follow whatever the humans were doing,” Acosta-Rodriguez said.

But now, from Rijo-Ferreira’s work, we know that the parasites are the time-keepers.

Rijo-Ferreira plans to continue her work on malaria and sleeping sickness, and also is studying Toxoplasma gondii, which causes toxoplasmosis, an infection people often get from eating undercooked meat or coming into contact with cat feces. Although most people who are infected do not have symptoms, infants and people with weakened immune systems can get seriously ill. Toxoplasmosis during pregnancy may cause miscarriage or birth defects.

“We have now shown that two deadly parasites have clocks to keep track of time,” she said. “We believe this is likely to be the case for most pathogens and are currently investigating how it impacts Toxoplasma’s biology. Ultimately, our interests and expertises lie on parasitic infections, but I imagine these are also not the only ones.”