Dr. Mroj Alassaf named a 2023 Helen Hay Whitney Fellow

Award will allow Rajan Lab postdoc to study why fat sends mitochondrial components to the brain
Dr. Mroj Alassaf stands in front of the Seattle skyline
Dr. Mroj Alassaf wants to understand how mitochondrial components from fat affect brain health — and how fat ensures that its molecular packages reach the brain. Photo courtesy of Mroj Alassaf

Fat cells stockpile lipids, but they’re not inert storage silos. Fat is a dynamic tissue in constant communication with the body and brain. Fat cells send signals that help the brain assess nutrient stores and determine whether to conserve energy, expend it, or seek out more.

Our fat — how much of it we have, and how healthy it is — has been linked to the health of other organs, including the brain. But what connects fat to brain health remains unknown. Work from the laboratory of Fred Hutchinson Cancer Center biologist Akhila Rajan, PhD, suggests that mitochondria, the cell’s energy-generating power plants, could form one link between fat and overall health. Her team recently showed that — at least in fruit flies — a key mitochondrial component, bundled up by fat cells, ends up in the brain.

Rajan postdoctoral fellow Mroj Alassaf, PhD, recently received a three-year, $215,000 Helen Hay Whitney Foundation fellowship to figure out how mitochondrial components from fat can reach the brain and what influence they have its health. The work could have implications beyond merely unraveling a communication pathway between fat cells and brain cells, she said.

“We’ve always thought of mitochondria as being constrained by cell barriers,” Assaf said. Her studies will join a growing body of research that upend this limited conception of mitochondria and uncover new lines of communication between tissues around the body.

The Helen Hay Whitney Foundation supports early postdoctoral research training in basic biomedical sciences with the aim of increasing the number of imaginative, well-trained and dedicated medical scientsts. Alassaf meets these criteria, said Rajan.

“Mroj is incredibly collaborative and intellectually generous, and her ambitious project on fat-brain mitochondrial communication is in keeping with her vision and scientific talent,” she wrote.

Do mitochondria from fat influence brain health?

A neurobiologist by training, Alassaf joined Rajan’s team after showing in her graduate work how a new mitochondrial protein contributes to neuronal health. Rajan was intrigued by Alassaf’s proposal to study how mitochondrial components working outside of the cells in which they originated may mediate communication between organs, in particular fat tissue and brain tissue.

Alassaf quickly found that in fruit flies, which share more energy-sensing and regulating processes with people than you might expect, fat cells package components of a molecular complex called ATPsynthase and send them off to the brain.

“Neurons are very reliant on their mitochondria,” Alassaf said. “What I think we’re seeing is fat altering whole-brain metabolism by sending these mitochondrial particles.”

Fat itself can be metabolically healthy or unhealthy, and mitochondria from metabolically dysfunctional fat cells may themselves be damaged. Alassaf thinks that these mitochondrial packages could be conveying fat tissue’s health status to the brain.

Damaged mitochondria make more reactive oxygen species, or ROS, which are byproducts of mitochondrial energy production that can damage proteins and DNA. If brain cells are trying to use damaged mitochondrial components, they may be ramping up ROS and ROS-related damage as well. Alternatively, increased ROS may trigger protective responses in brain cells. Alassaf’s work will help reveal potential positive or negative impacts that fat mitochondrial components (whether healthy or damaged) may have on the brain — and how disrupting this line of communication between tissues could disrupt health.

Her findings could have wide-ranging applications. Alassaf plans to work out the proteins and biological pathways that get the mitochondrial proteins out of the fat, as well as those that ensure that these packages enter the brain. It’s notoriously difficult to get compounds into the brain: a layer of specialized cells that lie along the blood vessels of the brain help keep dangerous compounds and pathogens out. It can also prevent important drugs, like chemotherapies for brain cancer, from entering. Revealing the biological processes that animals like fruit flies use to shepherd compounds into the brain could help drug manufacturers working to improve drug delivery to the brain.

Support from the Helen Hay Whitney Fellowship will be critical as Alassaf wades into uncharted waters, she said: “It offers immense creative freedom.”

Read more about Fred Hutch achievements and accolades.

Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

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