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Three Brown researchers named co-principal investigators of institute on sex, aging in genomics

$12.5 million grant will be used to study sex differences in aging

Ashley Webb — co-principal investigator on the grant and assistant professor of molecular biology, cell biology and biochemistry at the University — studies molecular mechanisms of brain aging in her lab, using mice as model organisms.
Ashley Webb — co-principal investigator on the grant and assistant professor of molecular biology, cell biology and biochemistry at the University — studies molecular mechanisms of brain aging in her lab, using mice as model organisms.

With a $12.5 million National Science Foundation grant, researchers from Brown and other universities across the country will study the “evolution of aging differences between females and males,” according to an Aug. 1 NSF award description.

Eleven investigators — including three Brown researchers — are using the NSF grant to create the Integration Institute: Sex, Aging, Genomics & Evolutions. The institute, also known as IISAGE, has funding to last for five years, according to Nicole Riddle, the grant’s principal investigator and associate professor of biology at the University of Alabama at Birmingham.

“We will be investigating the mechanism and evolution of sex differences in aging in a range of animal species (including) house flies and moths, fish, snakes, turtles, geckos, (mice) and bats,” Riddle wrote in an email to The Herald. The teams will investigate a variety of aging markers, including gene expression and mitochondrial function, to see if they change with age and might contribute to differences in aging between sexes, she added.

Each investigator’s lab has its own expertise and will collaborate within the institute. The funding distributed to each lab depends on what it contributes, Riddle wrote.

The goal of the grant is to figure out why sex so dramatically impacts age — a phenomenon that occurs across species, said Erica Larschan, co-principal investigator and associate professor of molecular biology, cell biology and biochemistry at the University. Scientists still don’t know why sex enables some animals to outlive other members of their species, she added.

“My research is really focused on how genes are turned on and off. The idea is to collect data on gene regulation from all these different species in male and females over time” and compare changes, Larschan said. Larschan and her team will bring their expertise in fruit flies and gene regulation processes to IISAGE.

Ashley Webb — co-principal investigator and assistant professor of molecular biology, cell biology and biochemistry at the University — studies molecular mechanisms of brain aging in her lab using mice as model organisms.

Webb’s lab started looking at female brains because they are generally understudied in science. “We’re at a point now where we should be studying both sexes, and so we felt there was a need to start looking at females,” she said. “Another reason is that lifespan is sexually dimorphic.”

“There are also neurodegenerative diseases, such as Alzheimer’s disease, where the disease is more prevalent in females than males … and we don’t have an idea of why that is,” Webb added. The lab plans to do more in-depth analysis comparing males and females to understand how regions of the brain change with age based on sex.

Ritambhara Singh, co-principal investigator and assistant professor of computer science at the University, is working on the computational biology side of the project.

“My lab’s contribution to the study will be to help the biologists make sense of their data from a machine learning perspective,” Singh said. “Our contribution will actually start around year three. Once we have the data, we will start working on predictive modeling.”

Her lab’s work will help reduce the “hypothesis space,” or the set of all possible hypotheses, by using machine learning models to guide the biologists in determining what factors will be important in their experiments, she added.

The researchers are especially looking forward to collaborating between the 11 laboratories.

“It’s important to highlight collaborative research and how exciting it can be,” Singh said. “This is where the world is moving, and collaboration is key in moving forward.”

The grant also includes an educational aspect, with part of the funding going toward programs for students to work on IISAGE projects, Larschan added. This includes additional funding for undergraduate summer research.

“I think the magic of the institute is the integration aspect. We can actually take all of our datasets and combine them together,” Webb said. “This is a really exciting opportunity for the investigators — the three of us at Brown — to come together and collaborate for the first time. We have really diverse approaches, … and we’re excited to work with the larger institute to expand and build on our results.”

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Jared Zhang

Jared is a Senior Staff Writer for Science and Research. He is a senior from Albuquerque, New Mexico studying physiology and biotechnology. Outside of The Herald he likes to fish, ride bikes and research the role of metals in human health and disease.



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