The National Science Foundation (NSF) named Feng Zhang the 2014 recipient of its Alan T. Waterman Award. This award is NSF’s highest honor that annually recognizes an outstanding researcher under the age of 35 and funds his or her research in any field of science or engineering. Zhang’s research focuses on understanding how the brain works.
“It is a great pleasure to honor Feng Zhang with this award for his young, impressive career,” said NSF Director France Córdova. “It is exciting to support his continued fundamental research, which is certain to impact the field of brain research. Imagine a future free of schizophrenia, autism and other brain disorders that wreak havoc on individuals, families and society. Feng’s research moves us in that direction.”
Zhang seeks to understand the molecular machinery of brain cells through the development and application of innovative technologies. He created and is continuing to perfect tools that afford researchers precise control over biological activities occurring inside the cell. With these tools, researchers can deepen their understanding of how the genome works, and how it influences the development and function of the brain. Zhang also examines failures within the systems that cause disease.
Two different lines of fundamental research and technology development are helping him do that: optogenetics and genome engineering. With Edward Boyden and Karl Deisseroth at Stanford University, he developed optogenetics to study brain circuits, a technique in which light is used to affect signaling and gene expression of neurons involved in complex behaviors. Zhang also developed the CRISPR system to enable new, cheaper, more effective ways to “edit” animal genomes–that is, to identify and cut a short DNA sequence underlying a disorder so that it may be deleted or substituted out for other genetic material. Although Zhang’s main area of focus is the brain, the potential applications of CRISPR technology extend well beyond neuroscience.
“This is an immensely exciting time for the field because of the tremendous potential of tools like CRISPR, which allows us to modify the genomes of mammalian cells,” Zhang said. “One of my long-term goals is to better understand the molecular mechanisms of brain function and identify new ways to treat devastating neurological disorders.”
Since high school, Zhang has devoted his time, energy and intellectual prowess to developing ways to study and repair the nervous system. Today, he is one of 11 core faculty members at the Broad Institute of MIT and Harvard; an investigator at MIT’s McGovern Institute for Brain Research; and the W. M. Keck Career Development Professor with a joint appointment in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering.
Zhang is widely recognized for his pioneering work in optogenetics and genome editing. He shared the Perl/UNC Neuroscience Prize with Karl Deisseroth and Edward Boyden in 2012. In 2013, MIT Technology Review recognized him as a “pioneer” and one of its 35 Innovators Under 35; Popular Science magazine placed Zhang on its Brilliant 10, an annual list of the most promising scientific innovators. Nature also named him as one of the “ten people who mattered” in 2013 for his work on developing the CRISPR system for genome editing in mammalian cells.
The Waterman award will be presented to Zhang at an evening ceremony at the U.S. Department of State in Washington, D.C., on May 6. At that event, the National Science Board will also present its 2014 Vannevar Bush award to mathematician Richard Tapia and Public Service awards to bioethicist Arthur Caplan and to the AAAS Science & Technology Policy Fellowships Program.
Plans are underway for Zhang to deliver a lecture at a meeting of the National Science Board at NSF and to meet with students at Thomas Jefferson High School for Science and Technology during his visit this spring.
Picking out a face in the crowd is a complicated task: Your brain has to retrieve the memory of the face you’re seeking, then hold it in place while scanning the crowd, paying special attention to finding a match.
A new study by MIT neuroscientists reveals how the brain achieves this type of focused attention on faces or other objects: A part of the prefrontal cortex known as the inferior frontal junction (IFJ) controls visual processing areas that are tuned to recognize a specific category of objects, the researchers report in the April 10 online edition of Science.
Scientists know much less about this type of attention, known as object-based attention, than spatial attention, which involves focusing on what’s happening in a particular location. However, the new findings suggest that these two types of attention have similar mechanisms involving related brain regions, says Robert Desimone, the Doris and Don Berkey Professor of Neuroscience, director of MIT’s McGovern Institute for Brain Research, and senior author of the paper.
“The interactions are surprisingly similar to those seen in spatial attention,” Desimone says. “It seems like it’s a parallel process involving different areas.”
In both cases, the prefrontal cortex — the control center for most cognitive functions — appears to take charge of the brain’s attention and control relevant parts of the visual cortex, which receives sensory input. For spatial attention, that involves regions of the visual cortex that map to a particular area within the visual field.
In the new study, the researchers found that IFJ coordinates with a brain region that processes faces, known as the fusiform face area (FFA), and a region that interprets information about places, known as the parahippocampal place area (PPA). The FFA and PPA were first identified in the human cortex by Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience at MIT.
The IFJ has previously been implicated in a cognitive ability known as working memory, which is what allows us to gather and coordinate information while performing a task — such as remembering and dialing a phone number, or doing a math problem.
For this study, the researchers used magnetoencephalography (MEG) to scan human subjects as they viewed a series of overlapping images of faces and houses. Unlike functional magnetic resonance imaging (fMRI), which is commonly used to measure brain activity, MEG can reveal the precise timing of neural activity, down to the millisecond. The researchers presented the overlapping streams at two different rhythms — two images per second and 1.5 images per second — allowing them to identify brain regions responding to those stimuli.
“We wanted to frequency-tag each stimulus with different rhythms. When you look at all of the brain activity, you can tell apart signals that are engaged in processing each stimulus,” says Daniel Baldauf, a postdoc at the McGovern Institute and the lead author of the paper.
Each subject was told to pay attention to either faces or houses; because the houses and faces were in the same spot, the brain could not use spatial information to distinguish them. When the subjects were told to look for faces, activity in the FFA and the IFJ became synchronized, suggesting that they were communicating with each other. When the subjects paid attention to houses, the IFJ synchronized instead with the PPA.
The researchers also found that the communication was initiated by the IFJ and the activity was staggered by 20 milliseconds — about the amount of time it would take for neurons to electrically convey information from the IFJ to either the FFA or PPA. The researchers believe that the IFJ holds onto the idea of the object that the brain is looking for and directs the correct part of the brain to look for it.
Further bolstering this idea, the researchers used an MRI-based method to measure the white matter that connects different brain regions and found that the IFJ is highly connected with both the FFA and PPA.
Members of Desimone’s lab are now studying how the brain shifts its focus between different types of sensory input, such as vision and hearing. They are also investigating whether it might be possible to train people to better focus their attention by controlling the brain interactions involved in this process.
“You have to identify the basic neural mechanisms and do basic research studies, which sometimes generate ideas for things that could be of practical benefit,” Desimone says. “It’s too early to say whether this training is even going to work at all, but it’s something that we’re actively pursuing.”
The research was funded by the National Institutes of Health and the National Science Foundation.
How accurate are our memories after a traumatic event? Does chronic stress make us more vulnerable to trauma? Will scientists one day succeed in preventing PTSD?
We invite you to join the discussion with a distinguished group of experts who will explore new lines of research and treatment strategies for stress disorders and traumatic memory. On Monday, April 7th, McGovern Institute director Bob Desimone will moderate a panel of experts and will engage the audience in a Q&A session. This event is free and open to the public, but registration is required. We hope you will join us!
– See more at: http://mcgovern.mit.edu/news/talks-events-news/fear-trauma-and-memory-a-panel-discussion/#sthash.Z8u0CLmP.dpuf
Chair: Alan Jasanoff, McGovern Institute
9:15 am – 9:55 am Alice Ting (Massachusetts Institute of Technology) Spatially-resolved proteomic mapping of living cells using engineered peroxidase reporters
9:55 am – 10:35 am Alex Shalek (Harvard University) Using single cell transcriptomics to explore cellular identity and uncover drivers of cellular behaviors watch video
10:35 am – 10:50 am
Break
10:50 am – 11:30 am Joseph Ecker (The Salk Institute) Global epigenomic reconfiguration during mammalian brain development
11:30 am – 12:10 pm Je Hyuk Lee (Harvard Medical School) Highly multiplexed subcellular RNA sequencing in situ watch video
12:10 pm – 1:00 pm
Break
Session II
Chair: Gloria Choi, McGovern Institute
1:00 pm – 1:40 pm Connie Cepko (Harvard University) GFP as a regulator of biological activities watch video
1:40 pm – 2:20 pm Kwanghun Chung (Massachusetts Institute of Technology) CLARITY and beyond: Towards fully-integrated multi-dimensional investigation of the brain
3:15 pm – 3:55 pm Michael Lin (Stanford University) GFP as an optogenetic Swiss Army knife: new applications in voltage sensing, memory visualization, and optical control of protein activity watch video
3:55 pm – 4:35 pm Loren Looger (HHMI, Janelia Farm) New tools for imaging and controlling neurons in vivo
4:35 pm – 5:15 pm Charles Lieber (Harvard University) Nanoelectronics meets neuroscience: Novel tools for mapping to electronic therapeutics
SPEAKER: Xiaoqin Wang, PhD AFFILIATION: Professor of Biomedical Engineering and Neuroscience, Department of Biomedical Engineering, Johns Hopkins University School of Medicine
Director of Tsinghua-Johns Hopkins Joint Center for Biomedical Engineering Research DATE + TIME: Thursday, April 10, 2014 @ 4:00 PM LOCATION: MIT Bldg 46-3002 (Singleton Auditorium) HOST: Guoping Feng, McGovern Institute
ABSTRACT:
Properly chosen animal models are pivotal in understanding brain mechanisms for behaviors. Research on the primate auditory system has been hampered for the lack of appropriate animal models with adequate vocal behaviors in laboratory conditions. We have developed a new model system to study neural basis of audition and vocal communication using the common marmoset (Callithrix jacchus), a highly vocal New World primate species. Marmosets have a rich repertoire of communication calls and remain highly vocal in captivity. Anatomically, marmosets have a smooth brain that provides easy access to many regions of the cerebral cortex for electrophysiological and optical recordings. They are easily bred and have a high reproductive rate, making it feasible to conduct developmental and transgenic studies. Using this unique model system, we have identified non-linear transformations of time-varying signals in auditory cortex and revealed harmonic organizations of this cortical region. We also showed that cortical representations of self-produced vocalizations are shaped by auditory feedback and vocal control signals during vocal communication. These findings have important implications for understanding how the brain processes speech and music and how it operates during speaking. They also demonstrate the potential of this non-human primate species in studying the neural basis of social interactions.
A photo montage of McGovern Institute co-founder Patrick J. McGovern. Pat McGovern passed away on March 19, 2014.
Photos: AP Images, Corbis, Donna Coveney, Robert Desimone, Jason Grow, IDG, Justin Knight, MIT News Office, MIT Sloan School of Management, MIT Yearbook, Dominick Reuter, Bethany Versoy.
Doctors commonly use magnetic resonance imaging (MRI) to diagnose tumors, damage from stroke, and many other medical conditions. Neuroscientists also rely on it as a research tool for identifying parts of the brain that carry out different cognitive functions.
Now, a team of biological engineers at MIT is trying to adapt MRI to a much smaller scale, allowing researchers to visualize gene activity inside the brains of living animals. Tracking these genes with MRI would enable scientists to learn more about how the genes control processes such as forming memories and learning new skills, says Alan Jasanoff, an MIT associate professor of biological engineering and leader of the research team.
“The dream of molecular imaging is to provide information about the biology of intact organisms, at the molecule level,” says Jasanoff, who is also an associate member of MIT’s McGovern Institute for Brain Research. “The goal is to not have to chop up the brain, but instead to actually see things that are happening inside.”
To help reach that goal, Jasanoff and colleagues have developed a new way to image a “reporter gene” — an artificial gene that turns on or off to signal events in the body, much like an indicator light on a car’s dashboard. In the new study, the reporter gene encodes an enzyme that interacts with a magnetic contrast agent injected into the brain, making the agent visible with MRI. This approach, described in a recent issue of the journal Chemical Biology, allows researchers to determine when and where that reporter gene is turned on.
An on/off switch
MRI uses magnetic fields and radio waves that interact with protons in the body to produce detailed images of the body’s interior. In brain studies, neuroscientists commonly use functional MRI to measure blood flow, which reveals which parts of the brain are active during a particular task. When scanning other organs, doctors sometimes use magnetic “contrast agents” to boost the visibility of certain tissues.
The new MIT approach includes a contrast agent called a manganese porphyrin and the new reporter gene, which codes for a genetically engineered enzyme that alters the electric charge on the contrast agent. Jasanoff and colleagues designed the contrast agent so that it is soluble in water and readily eliminated from the body, making it difficult to detect by MRI. However, when the engineered enzyme, known as SEAP, slices phosphate molecules from the manganese porphyrin, the contrast agent becomes insoluble and starts to accumulate in brain tissues, allowing it to be seen.
The natural version of SEAP is found in the placenta, but not in other tissues. By injecting a virus carrying the SEAP gene into the brain cells of mice, the researchers were able to incorporate the gene into the cells’ own genome. Brain cells then started producing the SEAP protein, which is secreted from the cells and can be anchored to their outer surfaces. That’s important, Jasanoff says, because it means that the contrast agent doesn’t have to penetrate the cells to interact with the enzyme.
Researchers can then find out where SEAP is active by injecting the MRI contrast agent, which spreads throughout the brain but accumulates only near cells producing the SEAP protein.
Exploring brain function
In this study, which was designed to test this general approach, the detection system revealed only whether the SEAP gene had been successfully incorporated into brain cells. However, in future studies, the researchers intend to engineer the SEAP gene so it is only active when a particular gene of interest is turned on.
Jasanoff first plans to link the SEAP gene with so-called “early immediate genes,” which are necessary for brain plasticity — the weakening and strengthening of connections between neurons, which is essential to learning and memory.
“As people who are interested in brain function, the top questions we want to address are about how brain function changes patterns of gene expression in the brain,” Jasanoff says. “We also imagine a future where we might turn the reporter enzyme on and off when it binds to neurotransmitters, so we can detect changes in neurotransmitter levels as well.”
Assaf Gilad, an assistant professor of radiology at Johns Hopkins University, says the MIT team has taken a “very creative approach” to developing noninvasive, real-time imaging of gene activity. “These kinds of genetically engineered reporters have the potential to revolutionize our understanding of many biological processes,” says Gilad, who was not involved in the study.
The research was funded by the Raymond and Beverly Sackler Foundation, the National Institutes of Health, and an MIT-Germany Seed Fund grant. The paper’s lead author is former MIT postdoc Gil Westmeyer; other authors are former MIT technical assistant Yelena Emer and Jutta Lintelmann of the German Research Center for Environmental Health.
Patrick McGovern was born in 1937 in Queens, New York, and grew up in New York and Philadelphia. He became interested in the brain as a teenager, when he came across a book titled “Giant Brains, or Machines that Think” in the Philadelphia public library. As he recalled in an interview some 50 years later, “It was the first book that talked about computers and their role as an amplifier of the human mind,” and it sparked a lifelong interest in science and technology. In 1955 Pat was admitted to MIT, where he majored in biophysics. He studied neurophysiology, and recalls using a glass electrode to study electrical activity in tadpoles. He also became involved in student newspapers, and after graduating from MIT in the class of 1959, he was hired as an assistant editor for a new magazine, “Computers and Automation,” founded by Ed Berkeley, the author of the book that had so intrigued him ten years earlier.
After four years as a magazine editor, Pat left to found his own company, now known as International Data Group (IDG), which under his leadership grew to become the world’s foremost publisher of computer-related news, information and research. IDG today is a multi-billion-dollar business, with 2013 revenues of over $3.5 billion. The story of Pat’s career at IDG has been often told, and his business accomplishments have been recognized with many honors, including lifetime achievement awards from American Business Media and from the Magazine Publishers of America. Yet despite his success and his imposing physical presence, Pat retained a modest demeanor and never cultivated the trappings of great wealth. Instead, he focused his energies on leadership of the company (of which he remained chairman until the time of his death) and increasingly in his later years, on his philanthropic priorities.
His career and fortune were made in computer technology, but never lost sight of his early dream to understand the brain, which he often described as the world’s most complex computer. When he studied neurophysiology at MIT in the 1950s, the tools were not adequate to the enormous challenge of understanding how the human brain works, but by the 1990s, technological progress had been so dramatic that the field had been transformed almost beyond recognition. A scientific understanding of the brain, while still a daunting challenge, was no longer within the realm of science fiction, but was a real prospect for the future.
Pat’s dream was shared by his wife Lore Harp McGovern, a Silicon Valley entrepreneur whose interests included healthcare, education and hi-tech. In the late 1990s they decided that the time was right to establish a new institute for brain research, and after consultations with many leading scientists and universities, they decided that the new institute would be at MIT.
Pat and Lore had both been longstanding MIT supporters; Pat was a member of the MIT Corporation, and Lore was chair of the Board of Associates at the affiliated Whitehead Institute. But they always emphasized that their choice of MIT was not simply a matter of loyalty to Pat’s alma mater. They felt that MIT was the right choice because of its alignment with their vision of a multidisciplinary, outward-looking institute that would engage the widest possible range of scientific talents in support of its mission to understand the brain. One goal was to understand the basis of brain disorders and to lay the foundation for new treatments for conditions such as psychiatric and neurodegenerative diseases – a goal that Pat and Lore considered vitally important, given the enormous suffering and economic costs that are inflicted by these disorders. But their vision was not confined to disease research; they also understood the brain to be the source of our humanity, our creative achievements and our conflicts, and they saw the possibility that understanding these things in scientific terms could transform the world for the better.
The McGovern Institute for Brain Research was formally established in 2000, with a commitment of $350 million from Pat and Lore, one of the largest philanthropic gifts in the history of higher education. Nobel laureate and Institute Professor Phillip A. Sharp, was named founding director, and Robert Desimone succeeded Sharp as director in 2004. In the fall of 2005, the McGovern Institute moved into spacious facilities in MIT’s Brain and Cognitive Sciences Complex, one of the most distinctive landmarks on the MIT campus and among the largest neuroscience research buildings in the world.
The McGovern Institute has continued to thrive since it moved to its new home, expanding in size and scope as it has hired new faculty and built new laboratories. Most importantly, it has produced a steady stream of discoveries about the working of the brain, in areas ranging from the genetic control of brain development to the neural basis of human thought and emotion. This progress was deeply gratifying to Pat and Lore, who visited regularly to attend the institute’s board meetings and scientific events, mingling with faculty and researchers and engaging deeply in discussions of their new findings. Throughout his life, Pat retained an extraordinary ability to absorb new information, and researchers were frequently impressed at his ability to cite detailed facts and figures about the brain. He was a tireless advocate for the institute and its mission, hosting many visits and tours, and inspiring others to follow his philanthropic example. He was, and Lore remains, an enormous source of inspiration and encouragement to the researchers at the institute.
Throughout Pat’s business career, his vision was global, and he took great pride in the fact that IDG was one of the first Western companies to establish a business presence in China after the end of the Cultural Revolution. It is thus fitting that Pat and Lore’s philanthropic vision also extended to China; since 2011, three new IDG/McGovern Institutes have been established in Beijing, at Tsinghua University, Peking (“Beida”) University and Beijing Normal University.
Like the McGovern Institute at MIT, the new institutes in China are focused on fundamental research in neuroscience as well as translational work on disease applications. Pat always saw brain disorders as global problems that required global solutions, and one of his greatest hopes was that the new institutes would help accelerate the international cooperation that he saw as essential to the ultimate goal of understanding the human brain in health and disease.
Pat’s wife Lore has been a full partner throughout the McGovern Institute’s 14-year history, serving on the governing board of the institute along with Pat and his daughter Elizabeth McGovern. All of us at the institute offer our deepest condolences to Lore, to their four children, and to all of Pat’s family members and friends. He will be greatly missed.
See below for a photo gallery of Pat McGovern.
Patrick McGovern with Lore Harp McGovern (right) and newscaster Jane Pauley, celebrating the 10th anniversary of the McGovern Institute in October 2010.
Patrick McGovern (left) with actor Alan Alda and producer Graham Chedd, at a screening of the PBS documentary ‘Brains on Trial’, September 2013.
Patrick McGovern (center) with (left to right) Wu Li (Beijing Normal University), Yi Rao (Peking University), Lore Harp McGovern, Robert Desimone (MIT) and Yi Zhong (Tsinghua University), at a joint symposium with the newly established IDG/McGovern Institutes in China, October 2013.
Patrick and Lore Harp McGovern at the 10th anniversary of the McGovern Institute, October 2010. Photo: Justin Knight
Patrick McGovern with researchers, at a McGovern Institute symposium with the newly established IDG/McGovern Institutes in China, October 2013.
Patrick McGovern at the 10th anniversary of the McGovern Institute, October 2010.
Patrick McGovern (right) with former MIT president Charles Vest at the 10th anniversary of the McGovern Institute, October 2010.
Patrick McGovern with his sister Laurette Verbinski at the 10th anniversary of the McGovern Institute, October 2010.
Patrick McGovern at the 10th anniversary of the McGovern Institute, October 2010.
Patrick McGovern (right) with actor Alan Alda and McGovern Institute director Robert Desimone, at a screening of the PBS documentary ‘Brains on Trial’, September 2013.
Pat McGovern, co-founder of the McGovern Institute for Brain Research at MIT.
