Three Israelis are among 35 honored this year by MIT with its annual list of young researchers who have had a huge impact on the world – and are expected to go on to do much more.
The three – Drs. Gilad Evrony, Cigall Kadoch, and Rikky Muller – all satisfy the main criteria of the prestigious Boston-based university, as “people who are driving the next generation of technological breakthroughs.”
MIT’s 35 Innovators Under 35 list has since 1999 selected young innovators whose work, the university believes, has great potential to transform the world. The awards, which cover fields such as biotechnology, materials, computer hardware, energy, transportation, communications and the web, were presented last week at EmTech, the annual conference of the MIT Technology Review.
Evrony was recognized for his work developing a new way to look at brain cells – analyzing the DNA of single neurons, in order to understand how they mutate, and how the brain grows and develops. The technology has shown that every person’s brain is sprinkled with countless genetic mutations invisible to prior research, “which may help explain some of the many neurologic and psychiatric diseases whose causes are not known,” Evrony told The Times of Israel.
A graduate of MIT, Evrony completed Harvard Medical School’s MD-PhD program where he worked in the laboratory of Christopher Walsh, chief of genetics and genomics at Boston Children’s Hospital. There he developed a way to read the tiny amount of DNA inside single brain cells, which led to a surprising discovery– that every neuron in a person’s brain contains many genetic mutations that occur as the brain develops in the womb and throughout life.
Early during his studies, Evrony managed to take off three years to serve in the IDF’s Intelligence Division, in the Israeli army’s elite communications and technology group whose graduates have made a huge impact on the Israeli start-up scene. “It was there I realized I could do this kind of work, where I was encouraged to think outside the box and learned the power of technology innovation,” Evrony said.
Working with the well-preserved brains of several people who died in accidents– including that of a 17-year-old– Evrony together with collaborators at Harvard performed “deep,” highly sensitive whole-genome sequencing of single neurons that identified so-called somatic mutations (genetic alterations that arise in the body during a person’s life).
“The common perception is that each cell in a person’s body has the same genetic code, but our single-cell sequencing shows that every cell in a person’s body is in fact genetically unique, carrying a unique fingerprint of mutations.”
Each mutation can have an effect on brain activity – or not. “We worked with a cluster of about 300 neurons one at a time, and even with that number we have seen a significant number of mutations,” Evrony said.
This technology promises to reveal how many genetic mutations there are in every cell in our bodies and brains, “a fundamental unknown” that Evrony says is important for “understanding the origins of all genetic diseases. By determining the rate of mutation, we will be able to see how they spread, and what their effects on the brain may be.”
Thus, said Evrony, it might be possible to trace the roots of some neurologic and psychiatric diseases, matching up mutations with causations, and in the future potentially reversing the mutations (with tools like CRISPR, a genetic editor).
By studying the patterns of how cells and mutations spread across the brain, scientists can now learn the relationship between cells, and between mutations and diseases, information that could point them toward solutions to problems like how brain diseases arise.
Using this technology, Evrony and colleagues have already found that mutations spread in interesting patterns in the brain so that every person’s brain is a “patchwork” of mutations. For example, some mutations can spread to only a small part of the brain.
“This means there may be subtle disorders nobody has thought to look for before where instead of the entire brain having a mutation only a small part does, such that only a specific aspect of a person’s intellect is affected,” Evrony added.
Taking on medical technology from another angle, Rikky Muller and her colleagues are focused on developing innovative medical devices to study and treat neurological disorders. Under her leadership, Cortera Neurotechnologies, a company she co-founded, is a key contributor to a DARPA program (as part of the Obama BRAIN initiative) aimed at developing neurotechnology as a therapy to treat neuropsychiatric disorders such as major depressive disorder and post traumatic stress disorder.
The World Health Organization estimates that such disorders account for up to 31 percent of the global burden of disease. Additionally, Cortera has developed a catalog of unique and commercially available products for neuroscientific research and discovery.
“I am delighted to receive this award and be included in this global community of innovators advancing technology for human benefit. My work involves developing devices that, among other things, lower surgical complexity and expand the patient population that can be treated for neurological disorders, thus improving and transforming their quality of life,” said Muller.
Meanwhile, while completing her PhD at Stanford, Cigall Kadoch discovered a link between a genome regulator in cells called the BAF protein complex and a rare cancer called synovial sarcoma. She and colleagues later showed that mutations of BAF are involved in at least 20 percent of human cancers, opening the door for research on drugs that target mutated BAFs.
BAF’s job in the cell is to open and close DNA to allow the right genes to be expressed at the right time. When mutated, it can “activate sites that it shouldn’t”—including genes that drive cancer, said Kadoch, who has appointments at Harvard Medical School and the Broad Institute of Harvard and MIT.
She learned this by focusing on one particular subunit of BAF. This piece of the protein has a deformed tail in 100 percent of patients with synovial sarcoma. When Kadoch put the deformed subunit into normal cells, she detected “blazing cancer,” she says. “That little tail is entirely responsible for this cancer.”
The good news is that this is reversible. Addiing enough normal pieces of the subunit to cells in a petri dish, she found, replaced the mutated form, killing the cancerous cells on the spot.
It’s technology to “fix” things that gets Evrony going – and it was part of the reason, he believes, that MIT decided to add his name to the 35 Under 35 list. “I’ve always believed in the power of new technologies to drive innovation in science,” Evrony said, “so it’s wonderful to be recognized by an award dedicated to technology innovation. This award represents the efforts of a wonderful team of scientists and my mentors who worked together to try something bold, hoping to make a lasting impact on medicine.”