By David
Shamah, The Times of Israel
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.”