Late Fall 2022
By Kathy Clute
Photography by Sam Ogden
Scientists are often able to pinpoint genomic variants in people with disease, but it is very difficult to understand which of those mutations caused their illness, and even harder to know how that knowledge should inform treatment. That’s why the Simons Foundation Autism Research Initiative (SFARI) awarded $1,179,895 to a project led by Dana-Farber cancer biologist Marc Vidal, PhD.
Vidal is director of the Institute’s Center for Cancer Systems Biology, where a multidisciplinary team of scientists is investigating how molecular networks within a cell control biological processes. They want to understand how disturbances of those networks can explain human disease.
With the SFARI grant, Vidal and his team are working to functionally characterize most variants in the SFARI gene set, which is strongly associated with autism spectrum disorder (ASD). Working with a computational biologist at the University of California, San Diego, their goal is to pinpoint the variants that are causing ASD and to provide insight into the underlying mechanisms by which that happens.
“We try to understand complex systems,” said Vidal. “The principles we’re hoping to learn here will help advance autism research as well as research on diseases like cancer.”
The New York-based Simons Foundation was founded in 1994 by Jim and Marilyn Simons to advance the frontiers of research in basic science and mathematics. Its SFARI initiative seeks to improve the understanding, diagnosis, and treatment of autism spectrum disorders by funding the most relevant and high-quality research in the field. SFARI has provided or committed more than $570 million in external research support to more than 600 investigators around the globe over the past two decades.
“This is important research, and we look forward to seeing the progress Dr. Vidal and his team will make toward improving the understanding of autism biology.”
— Kelsey Martin, Simons Foundation
“My lab is interested in trying to understand how proteins, RNA molecules, genes, the macromolecules of the cell—how they’re all organized,” Vidal explained. “The genome of cancer cells is totally perturbed relative to the genome of our healthy cells. And even different cells inside the same tumor don’t have the same genome. At the end, what we’re interested in is how the cell organizes all its molecules.”
Vidal compares studying just one discrete part of a cell to examining only one component of an airplane to understand how the plane stays aloft, posing the question, “How do we take mutations we see in the genome and characterize how these mutations affect the systems properties, the network properties of the cell?”
One intriguing finding from previous work by Vidal’s lab and others is that disparate diseases with little resemblance to one another often have genes in common. “Molecules are in very complex networks, and to perturb them in one way means cancer, but to disturb them in another way might produce Alzheimer’s disease or other disease,” he said.
“This is important research, and we look forward to seeing the progress Dr. Vidal and his team will make toward improving the understanding of autism biology,” said Kelsey Martin, director of SFARI and Simons Foundation Neuroscience Collaborations. “The results of this work will provide a better understanding of the causes and mechanisms of autism, which is vital to developing new therapeutic approaches.”