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Breaking down the Parkinson’s pathway

Anne Trafton |

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

Anne Trafton |

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

by Charles Jennings |

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.

Neuroscience and the Year of the Snake

Anne Trafton |

In the Chinese calendar, 2013 is the Year of the Snake, and to celebrate we’ve compiled a list of interesting facts about how snakes have contributed to brain research. [Click for English version of graphic.]

Snake venom

Snake venom has been a rich source of reagents for neuroscience research. Venom from the many-banded krait, a species found in Taiwan and Southern China, led to the identification of the first neurotransmitter receptor. In 1963 Chang and Lee at the National Taiwan University isolated a toxin, known as alpha-bungarotoxin, that binds strongly to the receptor for acetylcholine, the main neurotransmitter at neuromuscular synapses. This toxin, used by snakes to paralyze their victims’ muscles, was used by researchers to purify the acetylcholine receptor, and is still widely used today to study the biology of synapses.

Snake venom played central role in the identification of nerve growth factor (NGF) by Stanley Cohen and Rita Levi-Montalcini, who shared the 1986 Nobel Prize for their work. They discovered that the venom of the moccasin snake (a species of pit viper from the Southeastern US) was a rich source of a factor that could induce outgrowth of fibers from cultured neurons. This enabled them to characterize and eventually purify NGF, the first growth factor to be identified and the prototype for a large family of signaling molecules.

Snake venom has also led to several important advances in pain research, an area of great therapeutic interest. A protein complex isolated from the Texas coral snake has recently been shown to activate acid-sensitive ion channels (ASICs) in pain neurons, which is why bites from these snakes are so painful.  A peptide from the venom of a different species (the black mamba of East Africa, among the most venomous of all snakes) blocks the same channels and shows powerful analgesic effects – suggesting a promising new direction for drug development.

There are hundreds of species of venomous snakes, whose venoms contain a rich diversity of substances that have evolved specifically to interfere with the nervous systems of their victims and predators – a diversity that has only begun to be explored.

Snake evolution and behavior

Several families of snakes, including pit vipers, boas and pythons, can hunt at night using infrared (IR) radiation emitted by their warm-blooded prey. This ability arises from pit organs below the eyes, which allow these snakes to locate IR sources, sometimes with great accuracy. The molecular basis of IR detection was recently identified, and found to be an ion channel of the TRP family that is highly sensitive to warmth. The corresponding channel in other species is not strongly temperature-sensitive and is used mainly to detect chemical irritants (in humans, it responds to wasabi and mustard).  During snake evolution the same channel appears to have been co-opted for IR detection on several independent occasions in different snake families.

Another example of the evolutionary flexibility of brain and behavior comes from the tentacled snake of South-East Asia. This species hunts underwater, lying in wait for fish and detecting their location through a combination of vision and vibration. The snake captures a fish by exploiting its startle reflex – by making a feint with its body, the snake induces the fish to make a stereotypical escape response, directly toward the snake’s jaws. The snake can predict the fish’s behavior and makes a lunge to swallow it, all within about 25ms, or 1/40th second [video]. Remarkably a naïve snake, raised in captivity with no prior experience of fish, can do the same. Thus, the snake’s brain has been pre-wired by evolution to perform this behavior without the need for learning.

Snake phobia

Some people have a phobia for snakes, as do some animals, providing a useful model for understanding the neural basis of fear and anxiety. In one study, researchers even scanned volunteer subjects as they confronted a live snake inside the MRI scanner. These phobic responses are at least partly innate; monkeys, for example, will respond fearfully to a snake-like object even if they have never encountered one before. This raises interesting questions about how our brains are pre-wired to recognize specific stimuli, and also provides an opportunity to study how innate and leaned responses interact to control behavior.

These days snakes have more to fear from humans than vice versa, and many species around the world are now endangered. Awareness of their biology and potential for neuroscience discovery may strengthen efforts to conserve these remarkable creatures.

What do snakes have to do with neuroscience?

Anne Trafton |

In the Chinese calendar, 2013 is the Year of the Snake, and to celebrate we’ve compiled a list of interesting facts about how snakes have contributed to brain research. [Click for Chinese version of graphic.]

Snake venom

Snake venom has been a rich source of reagents for neuroscience research. Venom from the many-banded krait, a species found in Taiwan and Southern China, led to the identification of the first neurotransmitter receptor. In 1963 Chang and Lee at the National Taiwan University isolated a toxin, known as alpha-bungarotoxin, that binds strongly to the receptor for acetylcholine, the main neurotransmitter at neuromuscular synapses. This toxin, used by snakes to paralyze their victims’ muscles, was used by researchers to purify the acetylcholine receptor, and is still widely used today to study the biology of synapses.

Snake venom played central role in the identification of nerve growth factor (NGF) by Stanley Cohen and Rita Levi-Montalcini, who shared the 1986 Nobel Prize for their work. They discovered that the venom of the moccasin snake (a species of pit viper from the Southeastern US) was a rich source of a factor that could induce outgrowth of fibers from cultured neurons. This enabled them to characterize and eventually purify NGF, the first growth factor to be identified and the prototype for a large family of signaling molecules.

Snake venom has also led to several important advances in pain research, an area of great therapeutic interest. A protein complex isolated from the Texas coral snake has recently been shown to activate acid-sensitive ion channels (ASICs) in pain neurons, which is why bites from these snakes are so painful.  A peptide from the venom of a different species (the black mamba of East Africa, among the most venomous of all snakes) blocks the same channels and shows powerful analgesic effects – suggesting a promising new direction for drug development.

There are hundreds of species of venomous snakes, whose venoms contain a rich diversity of substances that have evolved specifically to interfere with the nervous systems of their victims and predators – a diversity that has only begun to be explored.

Snake evolution and behavior

Several families of snakes, including pit vipers, boas and pythons, can hunt at night using infrared (IR) radiation emitted by their warm-blooded prey. This ability arises from pit organs below the eyes, which allow these snakes to locate IR sources, sometimes with great accuracy. The molecular basis of IR detection was recently identified, and found to be an ion channel of the TRP family that is highly sensitive to warmth. The corresponding channel in other species is not strongly temperature-sensitive and is used mainly to detect chemical irritants (in humans it responds to wasabi and mustard).  During snake evolution the same channel appears to have been co-opted for IR detection on several independent occasions in different snake families.

Another example of the evolutionary flexibility of brain and behavior comes from the tentacled snake of South-East Asia. This species hunts underwater, lying in wait for fish and detecting their location through a combination of vision and vibration. The snake captures a fish by exploiting its startle reflex – by making a feint with its body, the snake induces the fish to make a stereotypical escape response, directly toward the snake’s jaws. The snake can predict the fish’s behavior and makes a lunge to swallow it, all within about 25ms, or 1/40th second [video]. Remarkably a naïve snake, raised in captivity with no prior experience of fish, can do the same. Thus, the snake’s brain has been pre-wired by evolution to perform this behavior without the need for learning.

Snake phobia

Some people have a phobia for snakes, as do some animals, providing a useful model for understanding the neural basis of fear and anxiety. In one study, researchers even scanned volunteer subjects as they confronted a live snake inside the MRI scanner. These phobic responses are at least partly innate; monkeys, for example, will respond fearfully to a snake-like object even if they have never encountered one before. This raises interesting questions about how our brains are pre-wired to recognize specific stimuli, and also provides an opportunity to study how innate and leaned responses interact to control behavior.

These days snakes have more to fear from humans than vice versa, and many species around the world are now endangered. Awareness of their biology and potential for neuroscience discovery may strengthen efforts to conserve these remarkable creatures.

Gloria Choi joins the McGovern Institute

Anne Trafton |

We are pleased to announce the appointment of Gloria Choi as a new McGovern Investigator, starting in summer 2013. She will also be an assistant professor in the MIT Department of Brain and Cognitive Sciences. Choi’s research addresses the mechanisms by which the brain learns to recognize olfactory stimuli and to associate them with appropriate behavioral responses.

Much recent work has been devoted to the question of how the binding of odorant molecules to their receptors in the olfactory epithelium leads to the perception of odors. In other sensory modalities such as vision, touch or hearing, the primary sensory cortex shows a topographical organization in which stimulus features are systematically mapped on the cortical surface. In the piriform cortex, however, no such order has been found; while individual inputs to the cortex are tuned to specific odorants, their projections within the piriform cortex appears topographically random. Consistent with this, olfactory stimuli typically activate sparse ensembles of piriform cells, with no obvious spatial pattern. Yet somehow the brain must learn to recognize these apparently arbitrary spatial patterns of activity and to endow them with behavioral significance.

Choi uses the power of rodent molecular genetics to study how this happens. Using the optogenetic molecule Channelrhodopsin2, she has been able to activate sparse arbitrarily-chosen populations of neurons within the piriform cortex using direct light stimulation. She has shown that animals can learn to recognize and distinguish these artificial “smell-like” cues, which can be flexibly associated with either rewarding or aversive stimuli to drive the appropriate behavioral responses.

In her own lab at MIT, Choi plans to dissect the brain circuits underlying this behavior, to understand how sensory representations in piriform cortex can drive downstream targets to generate learned behavioral responses. She also plans to extend her approach to study social behavior, which in rodents is strongly affected by olfactory cues. One important modulator of social behavior is the hormone oxytocin, and Choi plans to study how oxytocin may control the mechanisms by which animals learn to attribute social significance to olfactory stimuli.

Olfactory learning also provides an opportunity to study more general questions about how the brain learns to categorize sensory stimuli and to associate them with complex rule-based behaviors. Such cognitive processes have been linked to the prefrontal cortex in humans and other species, and olfactory behavior in mice may offer a new and genetically tractable system for exploring these issues.

Choi received her bachelor’s degree from University of California, Berkeley, and her Ph.D. from Caltech, where she studied with David Anderson. She is currently a postdoctoral research scientist in the laboratory of Richard Axel at Columbia University.

Editing the genome with high precision

Anne Trafton |

Researchers at MIT, the Broad Institute and Rockefeller University have developed a new technique for precisely altering the genomes of living cells by adding or deleting genes. The researchers say the technology could offer an easy-to-use, less-expensive way to engineer organisms that produce biofuels; to design animal models to study human disease; and to develop new therapies, among other potential applications.

To create their new genome-editing technique, the researchers modified a set of bacterial proteins that normally defend against viral invaders. Using this system, scientists can alter several genome sites simultaneously and can achieve much greater control over where new genes are inserted, says Feng Zhang, an assistant professor of brain and cognitive sciences at MIT and leader of the research team.

“Anything that requires engineering of an organism to put in new genes or to modify what’s in the genome will be able to benefit from this,” says Zhang, who is a core member of the Broad Institute and MIT’s McGovern Institute for Brain Research.

Zhang and his colleagues describe the new technique in the Jan. 3 online edition of Science. Lead authors of the paper are graduate students Le Cong and Ann Ran.

Early efforts

The first genetically altered mice were created in the 1980s by adding small pieces of DNA to mouse embryonic cells. This method is now widely used to create transgenic mice for the study of human disease, but, because it inserts DNA randomly in the genome, researchers can target the newly delivered genes to replace existing ones.

In recent years, scientists have sought more precise ways to edit the genome. One such method, known as homologous recombination, involves delivering a piece of DNA that includes the gene of interest flanked by sequences that match the genome region where the gene is to be inserted. However, this technique’s success rate is very low because the natural recombination process is rare in normal cells.

More recently, biologists discovered that they could improve the efficiency of this process by adding enzymes called nucleases, which can cut DNA. Zinc fingers are commonly used to deliver the nuclease to a specific location, but zinc finger arrays can target every possible sequence of DNA, limiting their usefulness. Furthermore, assembling the proteins is a labor-intensive and expensive process.

Complexes known as transcription activator-like effector nucleases (TALENs) can also cut the genome in specific locations, but these complexes can also be expensive and difficult to assemble.

Precise targeting

The new system is much more user-friendly, Zhang says. Making use of naturally occurring bacterial protein-RNA systems that recognize and snip viral DNA, the researchers can create DNA-editing complexes that include a nuclease called Cas9 bound to short RNA sequences. These sequences are designed to target specific locations in the genome; when they encounter a match, Cas9 cuts the DNA.

This approach can be used either to disrupt the function of a gene or to replace it with a new one. To replace the gene, the researchers must also add a DNA template for the new gene, which would be copied into the genome after the DNA is cut.

Each of the RNA segments can target a different sequence. “That’s the beauty of this. You can easily program a nuclease to target one or more positions in the genome,” Zhang says.

The method is also very precise — if there is a single base-pair difference between the RNA targeting sequence and the genome sequence, Cas9 is not activated. This is not the case for zinc fingers or TALENs. The new system also appears to be more efficient than TALEN, and much less expensive.

The new system “is a significant advancement in the field of genome editing and, in its first iteration, already appears comparable in efficiency to what zinc finger nucleases and TALENs have to offer,” says Aron Geurts, an associate professor of physiology at the Medical College of Wisconsin. “Deciphering the ever-increasing data emerging on genetic variation as it relates to human health and disease will require this type of scalable and precise genome editing in model systems.”

The research team has deposited the necessary genetic components with a nonprofit called Addgene, making the components widely available to other researchers who want to use the system. The researchers have also created a website with tips and tools for using this new technique.

Engineering new therapies

Among other possible applications, this system could be used to design new therapies for diseases such as Huntington’s disease, which appears to be caused by a single abnormal gene. Clinical trials that use zinc finger nucleases to disable genes are now under way, and the new technology could offer a more efficient alternative.

The system might also be useful for treating HIV by removing patients’ lymphocytes and mutating the CCR5 receptor, through which the virus enters cells. After being put back in the patient, such cells would resist infection.

This approach could also make it easier to study human disease by inducing specific mutations in human stem cells. “Using this genome editing system, you can very systematically put in individual mutations and differentiate the stem cells into neurons or cardiomyocytes and see how the mutations alter the biology of the cells,” Zhang says.

In the Science study, the researchers tested the system in cells grown in the lab, but they plan to apply the new technology to study brain function and diseases.

The research was funded by the National Institute of Mental Health; the W.M. Keck Foundation; the McKnight Foundation; the Bill & Melinda Gates Foundation; the Damon Runyon Cancer Research Foundation; the Searle Scholars Program; and philanthropic support from MIT alumni Mike Boylan and Bob Metcalfe, as well as the newscaster Jane Pauley.

Brain Scan Cover Image: Fall 2012

Anne Trafton |

Neurons in the brain of a transgenic mouse engineered to express a protein that emits light when neurons become active. Image: Qian Chen, Guoping Feng

Satra Ghosh: Social Engineer

Anne Trafton |

Satra Ghosh is a research scientist in John Gabrieli’s lab at the McGovern Institute for Brain Research at MIT. In this video, Satra talks about his research on mild traumatic brain injury in U.S. soldiers.

[Stock footage/music: U.S. Department of Defense, Satra Ghosh, shockwave-sound.com]