President Barack Obama greets the 2012 U.S. Kavli Prize Laureates in the Oval Office, March 28, 2013.
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Obama hosts Dresselhaus, Graybiel and Luu in Oval Office
President Barack Obama met Thursday, March 28, in the Oval Office with the six U.S. recipients of the 2012 Kavli Prizes — including MIT’s Mildred S. Dresselhaus, Ann M. Graybiel and Jane X. Luu. Obama and his science and technology advisor, John P. Holdren, received the scientists to recognize their landmark contributions in nanoscience, neuroscience and astrophysics, respectively. [watch video]
“American scientists, engineers and innovators strengthen our nation every day and in countless ways, but the all-stars honored by the Kavli Foundation deserve special praise for the scale of their advances in some of the most important and exciting research disciplines today,” said Holdren, who also serves as director of the White House Office of Science and Technology Policy. “I am grateful not only for their profound accomplishments, but for the inspiration they are providing to a new generation of doers, makers and discoverers.”
The researchers received their Kavli Prizes for making fundamental contributions to our understanding of the outer solar system; of the differences in material properties at nano- and larger scales; and of how the brain receives and responds to sensations such as sight, sound and touch.
The 2012 Kavli Prize in Astrophysics was awarded to Luu, David C. Jewitt of the University of California at Los Angeles, and Michael E. Brown of the California Institute of Technology for discovering and characterizing the Kuiper Belt and its largest members, work that led to a major advance in the understanding of the history of our planetary system. The Kuiper Belt lies beyond the orbit of Neptune and is a disk of more than 70,000 small bodies made of rock and ice, and orbiting the sun. Jewitt and Luu discovered the Kuiper Belt, and Brown discovered and characterized many of its largest members.
The 2012 Kavli Prize in Nanoscience was awarded to Dresselhaus for her work explaining why the properties of materials structured at the nanoscale can vary so much from those of the same materials at larger dimensions. Her early work provided the foundation for later discoveries concerning the famous C60 buckyball, carbon nanotubes and graphene. Dresselhaus received the Kavli Prize for her research into uniform oscillations of elastic arrangements of atoms or molecules called phonons; phonon-electron interactions; and heat conductivity in nanostructures.
The 2012 Kavli Prize in Neuroscience was awarded to Graybiel, Cornelia Isabella Bargmann of Rockefeller University, and Winfried Denk of the Max Planck Institute for Medical Research, who have pioneered the study of how sensory signals pass from the point of sensation — whether the eye, the foot or the nose — to the brain, and how decisions are made to respond. Each working on different parts of the brain, and using different techniques and models, they have combined precise neuroanatomy with sophisticated functional studies to gain understanding of their chosen systems.
MIT researchers join Obama for brain announcement
Four MIT neuroscientists were among those invited to the White House on Tuesday, April 2, when President Barack Obama announced a new initiative to understand the human brain.
Professors Ed Boyden, Emery Brown, Robert Desimone and Sebastian Seung were among a group of leading researchers who joined Obama for the announcement, along with Francis Collins, director of the National Institutes of Health, and representatives of federal and private funders of neuroscience research.
In unveiling the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, Obama highlighted brain research as one of his administration’s “grand challenges” — ambitious yet achievable goals that demand new innovations and breakthroughs in science and technology.
A key goal of the BRAIN Initiative will be to accelerate the development of new technologies to visualize brain activity and to understand how this activity is linked to behavior and to brain disorders.
“There is this enormous mystery waiting to be unlocked,” Obama said, “and the BRAIN Initiative will change that by giving scientists the tools they need to get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember. And that knowledge could be — will be — transformative.”
To jump-start the initiative, the NIH, the Defense Advanced Research Projects Agency, and the National Science Foundation will invest some $100 million in research support beginning in the next fiscal year. Planning will be overseen by a working group co-chaired by Cornelia Bargmann PhD ’87, now at Rockefeller University, and William Newsome of Stanford University. Brown, an MIT professor of computational neuroscience and of health sciences and technology, will serve as a member of the working group.
Boyden, the Benesse Career Development Associate Professor of Research in Engineering, has pioneered the development of new technologies for studying brain activity. Desimone, the Doris and Don Berkey Professor of Neuroscience, is director of MIT’s McGovern Institute for Brain Research, which conducts research in many areas relevant to the new initiative. Seung, a professor of computational neuroscience and physics, is a leader in the field of “connectomics,” the effort to describe the wiring diagram of the brain.
2013 Scolnick Prize Lecture: Thomas Jessell
Dr. Thomas Jessell of Columbia University is the winner of the 2013 Scolnick Prize in Neuroscience for his pioneering work on synaptic plasticity, the process by which the brain’s connections are modified in response to experience.
On April 1, 2013, he delivered the Scolnick Prize lecture, entitled “Sifting Circuits for Motor Control.”
Brain Scan Cover Image: Winter 2013
The cover of the Winter 2013 issue of Brain Scan features an artist’s representation of a new genome editing technique developed by Feng Zhang. The method allows researchers to disrupt or replace genes at will.
2013 Sharp Lecture in Neural Circuits: Karel Svoboda
On March 14, 2013, Dr. Karel Svoboda of HHMI delivered the second annual Sharp Lecture in Neuroscience. Dr. Svoboda’s lab is working on the structure, function and plasticity of neocortical circuits.
Martha Constantine-Paton to receive top honors from Tufts University
Martha Constantine-Paton will receive the Dean’s Medal from Tufts University’s School of Arts and Sciences for her “exceptional contributions to the field of developmental neuroscience.” Constantine-Paton, a Tufts alumna, refers to her time at the university as a “turning point” in her life and credits the school for giving her the self-confidence she needed to pursue a career in science. The Dean’s Medal is the highest honor available at each school at Tufts, reserved only “for those select individuals who have made outstanding contributions to the university and to the greater community.”
Constantine-Paton will be awarded the Dean’s Medal on March 25, 2013.
Breaking down the Parkinson’s pathway
The key hallmark of Parkinson’s disease is a slowdown of movement caused by a cutoff in the supply of dopamine to the brain region responsible for coordinating movement. While scientists have understood this general process for many years, the exact details of how this happens are still murky.
“We know the neurotransmitter, we know roughly the pathways in the brain that are being affected, but when you come right down to it and ask what exactly is the sequence of events that occurs in the brain, that gets a little tougher,” says Ann Graybiel, an MIT Institute Professor and member of MIT’s McGovern Institute for Brain Research.
A new study from Graybiel’s lab offers insight into some of the precise impairments caused by the loss of dopamine in brain cells affected by Parkinson’s disease. The findings, which appear in the March 12 online edition of the Journal of Neuroscience, could help researchers not only better understand the disease, but also develop more targeted treatments.
Lead author of the paper is Ledia Hernandez, a former MIT postdoc. Other authors are McGovern Institute research scientists Yasuo Kubota and Dan Hu, former MIT graduate student Mark Howe and graduate student Nuné Lemaire.
Cutting off dopamine
The neurons responsible for coordinating movement are located in a part of the brain called the striatum, which receives information from two major sources — the neocortex and a tiny region known as the substantia nigra. The cortex relays sensory information as well as plans for future action, while the substantia nigra sends dopamine that helps to coordinate all of the cortical input.
“This dopamine somehow modulates the circuit interactions in such a way that we don’t move too much, we don’t move too little, we don’t move too fast or too slow, and we don’t get overly repetitive in the movements that we make. We’re just right,” Graybiel says.
Parkinson’s disease develops when the neurons connecting the substantia nigra to the striatum die, cutting off a critical dopamine source; in a process that is not entirely understood, too little dopamine translates to difficulty initiating movement. Most Parkinson’s patients receive L-dopa, which can substitute for the lost dopamine. However, the effects usually wear off after five to 10 years, and complications appear.
To study exactly how dopamine loss affects the striatum, the researchers disabled dopamine-releasing cells on one side of the striatum, in rats. This mimics what usually happens in the early stages of Parkinson’s disease, when dopamine input is cut off on only one side of the brain.
As the rats learned to run a T-shaped maze, the researchers recorded electrical activity in many individual neurons. The rats were rewarded for correctly choosing to run left or right as they approached the T, depending on the cue that they heard.
The researchers focused on two types of neurons: projection neurons, which send messages from the striatum to the neocortex to initiate or halt movement, and fast-spiking interneurons, which enable local communication within the striatum. Among the projection neurons, the researchers identified two subtypes — those that were active just before the rats began running, and those that were active during the run.
In the dopamine-depleted striatum, the researchers found, to their surprise, that the projection neurons still developed relatively normal activity patterns. However, they became even more active during the time when they were usually active (before or during the run). These hyper-drive effects were related to whether the rats had learned the maze task or not.
The interneurons, however, never developed the firing patterns seen in normal interneurons during learning, even after the rats had learned to run the maze. The local circuits were disabled.
Restoring neuron function
When the researchers then treated the rats with L-dopa, the drug restored normal activity in the projection neurons, but did not bring back normal activity in the interneurons. A possible reason for that is that those cells become disconnected by the loss of dopamine, so even when L-dopa is given, they can no longer shape the local circuits to respond to it.
This is the first study to show that the effects of dopamine loss depend not only on the type of neuron, but also on the phase of task behavior and how well the task has been learned, according to the researchers. To glean even more detail, Graybiel’s lab is now working on measuring dopamine levels in different parts of the brain as the dopamine-depleted rats learn new behaviors.
The lab is also seeking ways to restore function to the striatal interneurons that don’t respond to L-dopa treatment. The findings underscore the need for therapies that target specific deficiencies, says Joshua Goldberg, a senior lecturer in medical neurobiology at the Hebrew University of Jerusalem.
The new study “refines our appreciation of the complexity of [Parkinson’s],” says Goldberg, who was not part of the research team. “Graybiel’s team drives home the message that dopamine depletion, and dopamine replacement therapy, do not affect brain dynamics or behavior in a uniform fashion. Instead, their effect is highly context-dependent and differentially affects various populations of neurons.”
The research was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the National Parkinson Foundation, the Stanley H. and Sheila G. Sydney Fund, a Parkinson’s Disease Foundation Fellowship and a Fulbright Fellowship.
Ed Boyden to share prestigious brain prize
Ed Boyden, a faculty member in the MIT Media Lab and the McGovern Institute for Brain Research, was today named a recipient of the 2013 Grete Lundbeck European Brain Research Prize. The 1 million Euro prize is awarded for the development of optogenetics, a technology that makes it possible to control brain activity using light.
The Brain Prize is awarded annually by the Denmark-based Lundbeck Foundation for outstanding contributions to European neuroscience. Boyden is recognized for work done in collaboration with Karl Deisseroth at Stanford University, which builds on earlier discoveries by four European researchers: Ernst Bamberg, Georg Nagel and Peter Hegemann in Germany, and Gero Miesenböck, now in Oxford, U.K. The prize will be shared equally between all six researchers.
The idea of using light to control brain activity was suggested by Francis Crick in 1999, and Miesenbock performed a proof of concept demonstration in 2002, showing that light-sensitive proteins obtained from the eyes of fruit-flies could be used to activate mammalian neurons. A further breakthrough was enabled by the discovery of channelrhodopsin-2 (ChR2), a light-activated ion channel from a common pond algal species that had been characterized by Hegemann in Martinsried and by Nagel and Bamberg in Frankfurt.
The application of ChR2 to neuroscience was pioneered by Boyden and Deisseroth at Stanford University, where Deisseroth is now a faculty member. In a collaboration that began when Boyden was a graduate student and Deisseroth a postdoctoral fellow, they obtained the ChR2 gene from Nagel and Bamberg, expressed it in cultured neurons, and pulsed the dish with blue light to see whether it could trigger neural activity. The first experiment was performed in August 2004, and it worked first time; as Boyden recounted in a recent historical article, “serendipity had struck — the molecule was good enough in its wild-type form to be used in neurons right away.”
They reported this result in 2005, in a landmark paper in Nature Neuroscience that has now been cited more than 600 times. Their method, later dubbed “optogenetics,” is now used by hundreds of labs worldwide and is also being explored for a wide range of potential therapeutic applications. In announcing the Brain Prize, the chairman of the selection committee, Professor Colin Blakemore, described optogenetics as “arguably the most important technical advance in neuroscience in the past 40 years.”
Boyden joined the MIT faculty in 2006, where he is now the Benesse Career Development Professor in the Media Lab, with joint appointments at the McGovern Institute for Brain Research and in the Departments of Biological Engineering and Brain and Cognitive Sciences. His contributions have been recognized by numerous awards and honors, including the inaugural AF Harvey Prize and the 2011 Perl/UNC prize (shared with Karl Deisseroth and with Feng Zhang, also at MIT). He continues to develop novel optogenetic tools, along with many other technologies for understanding and manipulating neural circuits within the living brain.
Boyden’s work was supported by the Fannie and John Hertz Foundation, the Helen Hay Whitney Foundation, the McKnight Foundation, Jerry and Marge Burnett, DARPA and the Department of Defense, Google, Harvard/MIT Joint Grants Program in Basic Neuroscience, Human Frontiers Science Program, IET A. F. Harvey Prize, MIT McGovern Institute and MIT Media Lab, NARSAD, New York Stem Cell Foundation-Robertson Investigator Award, NIH, NSF, Paul Allen Distinguished Investigator in Neuroscience Award, Shelly Razin, SkTech, Alfred P. Sloan Foundation, the Society for Neuroscience Research Award for Innovation in Neuroscience (RAIN), and the Wallace H. Coulter Foundation.
Thomas Jessell named winner of 2013 Scolnick Prize
The Scolnick Prize is awarded annually by the McGovern Institute to recognize outstanding advances in the field of neuroscience.
“We congratulate Tom Jessell on this award,” says Robert Desimone, director of the McGovern Institute and chair of the selection committee. “He has been a pioneer in transforming developmental neuroscience from a descriptive to a mechanistic and molecular science.”
Jessell received his PhD from Cambridge University, and has held faculty appointments at Harvard Medical School and at Columbia University, where he is now the Claire Tow Professor of Neuroscience. He is also an investigator of the Howard Hughes Medical Institute.
Since moving to Columbia University in 1985, Jessell’s primary interest has been the embryonic development of the nervous system, specifically the spinal cord, which because of its relative simplicity and evolutionary conservation offers an ideal system for understanding general principles of neural development.
Jessell’s work has revealed the molecular mechanisms responsible for establishing the spatial organization of the spinal cord. He showed that the cord is shaped during embryonic development by diffusible signaling molecules known as “morphogens.” Two different classes of molecules are secreted by the most dorsal and ventral parts of the developing cord respectively, forming two opposing concentration gradients in the dorso-ventral axis. The concentrations of these signaling molecules provide “positional information” to embryonic cells, instructing them to differentiate in ways that are appropriate for their specific locations within the cord.
Jessell has also studied the molecular mechanisms by which developing cells respond to positional signals. Spinal motor neurons, for example, are known to cluster into “pools,” groups of neurons that form at stereotypic locations within the ventral spinal cord and which innervate a common target muscle. There are at least 50 different muscles in a vertebrate limb, each of which must be correctly innervated to allow precise control of movement. Jessell has shown that the identities of different motor pools are specified by combinations of transcription factors which are activated in different spatial domains in response to positional cues. These transcriptional “master regulators” work by controlling the expression of downstream genes that determine the distinctive properties of different neurons, including their shapes, their biochemical and electrical properties, and their choice of peripheral and central connections.
The discovery of these genetic mechanisms has made it possible to identify and manipulate the activity of specific classes of neurons with great precision, and Jessell has used this approach to reveal the link between functional circuitry and motor behavior. In addition to fundamental questions, Jessell’s work has important practical implications for the emerging field of regenerative medicine. There is great interest in stem cells as a renewable source of cells for transplantation therapy, but for this approach to succeed, stem cells must be converted to the desired cell type. Jessell’s work on transcriptional control of neural identity provides a roadmap for such efforts, and he has demonstrated its feasibility in the case of spinal motor neurons, which degenerate in diseases such as amyotrophic lateral sclerosis. In collaboration with his former postdoc Hynek Wichterle, Jessell recently showed that embryonic stem cells can be induced to form a wide variety of motor neuron subtypes, and that when these neurons are transplanted into host embryos they can settle at the correct locations in the spinal cord and form appropriate axonal projections toward their normal targets. The implications of this result go well beyond motor neuron diseases; many disorders of the nervous system affect particular cell types, and the ability to convert stem cells to specific classes of neurons may eventually find wide applications in clinical neuroscience.
In addition to his many research contributions, Jessell also had great influence as a teacher and mentor. He is a coauthor of the classic textbook Principles of Neural Science, now in its fifth edition, and he has trained dozens of students and postdocs, many of whom are now recognized leaders in the field of neural development. Among the most notable is Marc Tessier-Lavigne, now president of Rockefeller University, whose pioneering work on the molecular basis of axon guidance was begun during a postdoctoral fellowship in Jessell’s lab.
The McGovern Institute will award the Scolnick Prize to Dr Jessell on Monday April 1, 2013. At 4.00 pm he will deliver a lecture entitled “Sifting Circuits for Motor Control,” to be followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar Street (building 46, room 3002) in Cambridge. The event is free and open to the public.