“The Mother and Child is a powerful symbol of love and innocence, beauty and fertility. Although these maternal values, and the women who embody them, may be venerated, they are usually viewed in opposition to other values: inquiry and intellect, progress and power. But I am a neuroscientist, and I worked to create this image; and I am also the mother in it, curled up inside the tube with my infant son.” — Rebecca Saxe
MIT researchers took home several awards last night at the 2016 Breakthrough Prize ceremony at NASA’s Ames Research Center in Mountain View, California.
Edward Boyden, an associate professor of media arts and sciences, biological engineering, and brain and cognitive sciences, was one of five scientists honored with the Breakthrough Prize in Life Sciences, given for “transformative advances toward understanding living systems and extending human life.” He will receive $3 million for the award.
MIT physicists also contributed to a project that won the Breakthrough Prize in Fundamental Physics. That prize went to five experiments investigating the oscillation of subatomic particles known as neutrinos. More than 1,300 contributing physicists will share in the recognition for their work, according to the award announcement. Those physicists include MIT associate professor of physics Joseph Formaggio and his team, as well as MIT assistant professor of physics Lindley Winslow.
Larry Guth, an MIT professor of mathematics, was honored with the New Horizons in Mathematics Prize, which is given to promising junior researchers who have already produced important work in mathematics. Liang Fu, an assistant professor of physics, was honored with the New Horizons in Physics Prize, which is awarded to promising junior researchers who have already produced important work in fundamental physics.
“By challenging conventional thinking and expanding knowledge over the long term, scientists can solve the biggest problems of our time,” said Mark Zuckerberg, chairman and CEO of Facebook, and one of the prizes’ founders. “The Breakthrough Prize honors achievements in science and math so we can encourage more pioneering research and celebrate scientists as the heroes they truly are.”
Optogenetics
Boyden was honored for the development and implementation of optogenetics, a technique in which scientists can control neurons by shining light on them. Karl Deisseroth, a Stanford University professor who worked with Boyden to pioneer the technique, was also honored with one of the life sciences prizes.
Optogenetics relies on light-sensitive proteins, originally isolated from bacteria and algae. About 10 years ago, Boyden and Deisseroth began engineering neurons to express these proteins, allowing them to selectively stimulate or silence them with pulses of light. More recently, Boyden has developed additional proteins that are even more sensitive to light and can respond to different colors.
Scientists around the world have used optogenetics to reveal the brain circuitry underlying normal neural function as well as neurological disorders such as autism, obsessive-compulsive disorder, and depression.
Boyden is a member of the MIT Media Lab and MIT’s McGovern Institute for Brain Research.
Neutrino oscillations
The Breakthrough Prize in Fundamental Physics was awarded to five research projects investigating the nature of neutrinos: Daya Bay (China); KamLAND (Japan); K2K/T2K (Japan); Sudbury Neutrino Observatory (Canada); and Super-Kamiokande (Japan). Researchers with these experiments were recognized “for the fundamental discovery of neutrino oscillations, revealing a new frontier beyond, and possibly far beyond, the standard model of particle physics.”
Formaggio and his team at MIT have been collaborating on the Sudbury Neutrino Observatory (SNO) project since 2005. Research at the observatory, 2 kilometers underground in a mine near Sudbury, Ontario, demonstrated that neutrinos change their type — or “flavor” — on their way to Earth from the sun.
Winslow has been a collaborator on KamLAND, located in a mine in Japan, since 2001. Using antineutrinos from nuclear reactors, this experiment demonstrated that the change in flavor was energy-dependent. The combination of these results solved the solar neutrino puzzle and proved that neutrinos have mass.
The MIT SNO group has participated heavily on the analysis of neutrino data, particularly during that experiment’s final measurement phase. The MIT KamLAND group is involved with the next phase, KamLAND-Zen, which is searching for a rare nuclear process that if observed, would make neutrinos their own antiparticles.
Reaching new horizons
Guth, who will receive a $100,000 prize, was honored for his “ingenious and surprising solutions to long standing open problems in symplectic geometry, Riemannian geometry, harmonic analysis, and combinatorial geometry.”
Guth’s work at MIT focuses on combinatorics, or the study of discrete structures, and how sets of lines intersect each other in space. He also works in the area of harmonic analysis, studying how sound waves interact with each other.
Guth’s father, MIT physicist Alan Guth, won the inaugural Breakthrough Prize in Fundamental Physics in 2015.
Fu will share a New Horizons in Physics Prize with two other researchers: B. Andrei Bernevig of Princeton University and Xiao-Liang Qi of Stanford University. The physicists were honored for their “outstanding contributions to condensed matter physics, especially involving the use of topology to understand new states of matter.”
Fu works on theories of topological insulators — a new class of materials whose surfaces can freely conduct electrons even though their interiors are electrical insulators — and topological superconductors. Such materials may provide insight into quantum physics and have possible applications in creating transistors based on the spin of particles rather than their charge.
Yesterday’s prize ceremony was hosted by producer/actor/director Seth MacFarlane; awards were presented by the prize sponsors and by celebrities including actors Russell Crowe, Hilary Swank, and Lily Collins. The Breakthrough Prizes were founded by Sergey Brin and Anne Wojcicki, Jack Ma and Cathy Zhang, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan.
“Breakthrough Prize laureates are making fundamental discoveries about the universe, life, and the mind,” Yuri Milner said. “These fields of investigation are advancing at an exponential pace, yet the biggest questions remain to be answered.”
How does CRISPR work? Feng Zhang explains in this video produced by STAT.
Read Sharon Begley’s full story on Feng Zhang, the “most transformative biologist of his generation” on the STAT website.
MIT engineers have designed magnetic protein nanoparticles that can be used to track cells or to monitor interactions within cells. The particles, described today in Nature Communications, are an enhanced version of a naturally occurring, weakly magnetic protein called ferritin.
“Ferritin, which is as close as biology has given us to a naturally magnetic protein nanoparticle, is really not that magnetic. That’s what this paper is addressing,” says Alan Jasanoff, an MIT professor of biological engineering and the paper’s senior author. “We used the tools of protein engineering to try to boost the magnetic characteristics of this protein.”
The new “hypermagnetic” protein nanoparticles can be produced within cells, allowing the cells to be imaged or sorted using magnetic techniques. This eliminates the need to tag cells with synthetic particles and allows the particles to sense other molecules inside cells.
The paper’s lead author is former MIT graduate student Yuri Matsumoto. Other authors are graduate student Ritchie Chen and Polina Anikeeva, an assistant professor of materials science and engineering.
Magnetic pull
Previous research has yielded synthetic magnetic particles for imaging or tracking cells, but it can be difficult to deliver these particles into the target cells.
In the new study, Jasanoff and colleagues set out to create magnetic particles that are genetically encoded. With this approach, the researchers deliver a gene for a magnetic protein into the target cells, prompting them to start producing the protein on their own.
“Rather than actually making a nanoparticle in the lab and attaching it to cells or injecting it into cells, all we have to do is introduce a gene that encodes this protein,” says Jasanoff, who is also an associate member of MIT’s McGovern Institute for Brain Research.
As a starting point, the researchers used ferritin, which carries a supply of iron atoms that every cell needs as components of metabolic enzymes. In hopes of creating a more magnetic version of ferritin, the researchers created about 10 million variants and tested them in yeast cells.
After repeated rounds of screening, the researchers used one of the most promising candidates to create a magnetic sensor consisting of enhanced ferritin modified with a protein tag that binds with another protein called streptavidin. This allowed them to detect whether streptavidin was present in yeast cells; however, this approach could also be tailored to target other interactions.
The mutated protein appears to successfully overcome one of the key shortcomings of natural ferritin, which is that it is difficult to load with iron, says Alan Koretsky, a senior investigator at the National Institute of Neurological Disorders and Stroke.
“To be able to make more magnetic indicators for MRI would be fabulous, and this is an important step toward making that type of indicator more robust,” says Koretsky, who was not part of the research team.
Sensing cell signals
Because the engineered ferritins are genetically encoded, they can be manufactured within cells that are programmed to make them respond only under certain circumstances, such as when the cell receives some kind of external signal, when it divides, or when it differentiates into another type of cell. Researchers could track this activity using magnetic resonance imaging (MRI), potentially allowing them to observe communication between neurons, activation of immune cells, or stem cell differentiation, among other phenomena.
Such sensors could also be used to monitor the effectiveness of stem cell therapies, Jasanoff says.
“As stem cell therapies are developed, it’s going to be necessary to have noninvasive tools that enable you to measure them,” he says. Without this kind of monitoring, it would be difficult to determine what effect the treatment is having, or why it might not be working.
The researchers are now working on adapting the magnetic sensors to work in mammalian cells. They are also trying to make the engineered ferritin even more strongly magnetic.
To view the 2015 McGovern Institute Halloween Party gallery, please click on one of the thumbnail images below.
Imagine you are looking for your wallet on a cluttered desk. As you scan the area, you hold in your mind a mental picture of what your wallet looks like.
MIT neuroscientists have now identified a brain region that stores this type of visual representation during a search. The researchers also found that this region sends signals to the parts of the brain that control eye movements, telling individuals where to look next.
This region, known as the ventral pre-arcuate (VPA), is critical for what the researchers call “feature attention,” which allows the brain to seek objects based on their specific properties. Most previous studies of how the brain pays attention have investigated a different type of attention known as spatial attention — that is, what happens when the brain focuses on a certain location.
“The way that people go about their lives most of the time, they don’t know where things are in advance. They’re paying attention to things based on their features,” says Robert Desimone, director of MIT’s McGovern Institute for Brain Research. “In the morning you’re trying to find your car keys so you can go to work. How do you do that? You don’t look at every pixel in your house. You have to use your knowledge of what your car keys look like.”
Desimone, also the Doris and Don Berkey Professor in MIT’s Department of Brain and Cognitive Sciences, is the senior author of a paper describing the findings in the Oct. 29 online edition of Neuron. The paper’s lead author is Narcisse Bichot, a research scientist at the McGovern Institute. Other authors are Matthew Heard, a former research technician, and Ellen DeGennaro, a graduate student in the Harvard-MIT Division of Health Sciences and Technology.
Visual targets
The researchers focused on the VPA in part because of its extensive connections with the brain’s frontal eye fields, which control eye movements. Located in the prefrontal cortex, the VPA has previously been linked with working memory — a cognitive ability that helps us to gather and coordinate information while performing tasks such as solving a math problem or participating in a conversation.
“There have been a lot of studies showing that this region of the cortex is heavily involved in working memory,” Bichot says. “If you have to remember something, cells in these areas are involved in holding the memory of that object for the purpose of identifying it later.”
In the new study, the researchers found that the VPA also holds what they call an “attentional template” — that is, a memory of the item being sought.
In this study, the researchers first showed monkeys a target object, such as a human face, a banana, or a butterfly. After a delay, they showed an array of objects that included the target. When the animal fixed its gaze on the target object, it received a reward. “The animals can look around as long as they want until they find what they’re looking for,” Bichot says.
As the animals performed the task, the researchers recorded electrical activity from neurons in the VPA. Each object produced a distinctive pattern of neural activity, and the neurons that encoded a representation of the target object stayed active until a match was found, prompting the neurons to fire even more.
“When the target object finally enters their receptive fields, they give enhanced responses,” Desimone says. “That’s the signal that the thing they’re looking for is actually there.”
About 20 to 30 milliseconds after the VPA cells respond to the target object, they send a signal to the frontal eye fields, which direct the eyes to lock onto the target.
When the researchers blocked VPA activity, they found that although the animals could still move their eyes around in search of the target object, they could not find it. “Presumably it’s because they’ve lost this mechanism for telling them where the likely target is,” Desimone says.
Focused attention
The researchers believe the VPA may be the equivalent in nonhuman primates of a human brain region called the inferior frontal junction (IFJ). Last year Desimone and postdoc Daniel Baldauf found that the IFJ holds onto the idea of a target object — in that study, either faces or houses — and then directs the correct part of the brain to look for the target.
The researchers are now studying how the VPA interacts with a nearby region called the VPS, which appears to be more important for tasks in which attention must be switched quickly from one object to another. They are also performing additional studies of human attention, in hopes of learning more about disorders such as Attention Deficit Hyperactivity Disorder and other attention disorders.
“There’s really an opportunity there to understand something important about the role of the prefrontal cortex in both normal behavior and in brain disorders,” Desimone says.
