Category: Uncategorized

McGovern Institute Snowball Fight

Anne Trafton |

McGovern faculty, researchers and staff participated in a snowball fight in the Bldg 46 atrium. The scene was filmed for the annual McGovern holiday video greeting.

See below for a photo gallery of the event. All photos courtesy of Justin Knight.

Editas Medicine to develop new class of genome editing therapeutics

Anne Trafton |

Editas Medicine, a transformative genome editing company, today announced it has secured a $43 million Series A financing led by Flagship Ventures, Polaris Partners and Third Rock Ventures with participation from Partners Innovation Fund. Following an explosion of high profile publications on CRISPR/Cas9 and TALENs, genome editing has emerged as one of the most exciting new areas of scientific research. These recent advances have made it possible to modify, in a targeted way, almost any gene in the human body with the ability to directly turn on, turn off or edit disease-causing genes. Editas’ mission is to translate its genome editing technology into a novel class of human therapeutics that enable precise and corrective molecular modification to treat the underlying cause of a broad range of diseases at the genetic level.

“Editas is exclusively positioned to leverage the very latest in genome editing to develop life-changing medicines for patients,” said Kevin Bitterman, Ph.D., interim president, Editas Medicine and principal, Polaris Partners. “Our suite of foundational intellectual property, combined with the proprietary know-how of our founding team and our financial resources, will enable us to rapidly translate these groundbreaking discoveries into important medicines.”

Leading Foundational Science & Team

The company’s five founders have published much of the foundational work that has elevated genome editing technology to a level where it can now be optimized and developed for therapeutic use. Feng Zhang, Ph.D., core member of the Broad Institute, Investigator at the McGovern Institute for Brain Research and joint assistant professor in the Departments of Brain and Cognitive Sciences and Biological Engineering at Massachusetts Institute of Technology; George Church, Ph.D., founding core faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Robert Winthrop professor of genetics at Harvard Medical School; and Jennifer Doudna, Ph.D., Howard Hughes Medical Institute investigator and professor of biochemistry, biophysics and structural biology at the University of California, Berkeley, are eminent academic leaders who described and invented key elements of the CRISPR/Cas technology. Keith Joung, M.D., Ph.D., associate chief of pathology for research and associate pathologist at Massachusetts General Hospital and associate professor of pathology at Harvard Medical School, is a pioneer in the development and translation of genome editing technologies. David Liu, Ph.D., Howard Hughes Medical Institute investigator and professor of chemistry and chemical biology at Harvard University, is a renowned protein evolution and engineering biologist.

The company has generated substantial patent filings and has access to intellectual property covering foundational genome editing technologies, as well as essential advancements and enablements that will uniquely allow the company to translate early findings into viable human therapeutic products.

Dr. Zhang commented, “Advances in genome editing have opened the door for an entirely new and promising approach to treating disease by correcting causative errors directly in a patient’s genome. Editas is optimizing and refining existing genome editing technology to create a versatile platform for the development of potential human therapeutics.”

Genome Editing

CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) and TALENs (transcription activator-like effector nucleases) comprise novel gene editing methods that overcome the challenges associated with previous technologies. Early published research on CRISPR/Cas9, coupled with a growing body of work on TALENs, suggests the potential to pursue therapeutic indications that have previously been intractable to traditional gene therapy, gene knock-down or other genome modification techniques. The CRISPR/Cas9 system, the most recent and exciting approach to emerge, acts by a mechanism in which the Cas9 protein binds to specific RNA molecules. The RNA molecules then guide the Cas9 complex to the exact location in the genome that requires repair. CRISPR/Cas9 uniquely enables highly efficient knock-out, knock-down or selective editing of defective genes in the context of their natural promoters, unlocking the ability to treat the root cause of a broad range of diseases.

“Editas is poised to bring genome editing to fruition as a new therapeutic modality, essentially debugging errors in the human software that cause disease,” said Alexis Borisy, director, Editas Medicine and partner, Third Rock Ventures. “Our CRISPR/Cas9 technology is favorably differentiated due to its ability to pursue almost the entire genome, allowing broad therapeutic application and the targeting of defective genes in a highly specific, selective and efficient manner.”

Management and Board

In collaboration with its founders, Editas has assembled a leadership team and board of directors comprised of experienced investors and industry veterans with proven track records for building exceptional life sciences companies. In addition to Dr. Bitterman, the Editas leadership team includes Alexandra Glucksmann, Ph.D., interim chief operating officer and former founding employee and SVP of research and development at Cerulean Pharma; and Lou Tartaglia, Ph.D., interim chief scientific officer and partner, Third Rock Ventures.

The board of directors is composed of leaders from the Editas syndicate including Mr. Borisy; Douglas Cole, M.D., general partner, Flagship Ventures; and Terry McGuire, co-founder and general partner, Polaris Partners.

“The gene editing approaches on which Editas is based represent some of the most exciting and promising scientific breakthroughs in recent years, making it possible, for the first time, to correct the genomic defects responsible for a broad range of diseases,” said Dr. Cole. “The Editas syndicate has come together as a collaborative team dedicated to supporting and advancing the company’s revolutionary approach to improve patients’ lives. Our funds’ collective strength provides Editas the resources to translate this groundbreaking work into important therapeutics.”

About Flagship Ventures

Realizing entrepreneurial innovation is the mission of Flagship Ventures. The firm operates through two synergistic units: VentureLabs™ which invents and launches transformative companies, and Venture Capital, which finances and develops innovative, early-stage companies. Founded in 2000, and based in Cambridge, Massachusetts, Flagship Ventures manages over $900 million in capital. The Flagship team is active in three principal business sectors: therapeutics, health technologies and sustainability/clean technology. For more information, please visit www.flagshipventures.com.

About Polaris Partners

Founded in 1996, Polaris Partners has more than $3.5 billion in capital under management which we invest into a diverse portfolio of technology and healthcare companies throughout their lifecycles. From the earliest startup phases through the growth equity stages, Polaris Partners takes minority and majority positions alongside outstanding management teams to help grow industry leading companies like Ascend, Avila, Ironwood, Receptos, LogMeIn and Akamai. With offices in Boston, San Francisco and Dublin, Polaris partners with an unparalleled network of repeat CEOs, entrepreneurs, top scientists and emerging innovators who are positioned to make a significant impact in their fields and vastly improve the way in which we all live and work. The result: Hundreds of growing companies, thousands of jobs generated, and billions of dollars of value created. For more information, visit: www.polarispartners.com.

About Third Rock Ventures

Third Rock Ventures is a leading healthcare venture firm focused on investing and launching companies that make a difference in people’s lives. The Third Rock team has a unique vision for ideating and building transformative healthcare companies. Working closely with our strategic partners and entrepreneurs, Third Rock has an extensive track record for managing the value creation path to deliver exceptional performance. For more information, please visit the firm’s website at www.thirdrockventures.com.

About Partners Innovation Fund

The Partners Innovation Fund is the strategic venture fund for Partners HealthCare, founded by the Massachusetts General Hospital and Brigham and Women’s Hospital. The mission of the fund is to provide the necessary support to commercialize innovations in medical informatics, diagnostics, drugs and devices that emerge from the Partners HealthCare investigator community.

Sheng Li: McGovern Institute 2013 Fall Symposium

Anne Trafton |

Sheng Li, Peking University
“Reward modulation of attention & working memory in the human brain.”

On November 4, the McGovern Institute for Brain Research at MIT hosted a joint symposium with the IDG/McGovern Institutes at Beijing Normal University, Peking University, and Tsinghua University. Guest speakers gave talks on subjects ranging from learning and memory to the neurobiology of disease. The symposium was sponsored by the McGovern Institutes and Hugo Shong.

McGovern neuroscientists discover new role for ‘hunger hormone’

Anne Trafton |

About a dozen years ago, scientists discovered that a hormone called ghrelin enhances appetite. Dubbed the “hunger hormone,” ghrelin was quickly targeted by drug companies seeking treatments for obesity — none of which have yet panned out.

MIT neuroscientists have now discovered that ghrelin’s role goes far beyond controlling hunger. The researchers found that ghrelin released during chronic stress makes the brain more vulnerable to traumatic events, suggesting that it may predispose people to posttraumatic stress disorder (PTSD).

Drugs that reduce ghrelin levels, originally developed to try to combat obesity, could help protect people who are at high risk for PTSD, such as soldiers serving in war, says Ki Goosens, an assistant professor of brain and cognitive sciences at MIT, and senior author of a paper describing the findings in the Oct. 15 online edition of Molecular Psychiatry.

“Perhaps we could give people who are going to be deployed into an active combat zone a ghrelin vaccine before they go, so they will have a lower incidence of PTSD. That’s exciting because right now there’s nothing given to people to prevent PTSD,” says Goosens, who is also a member of MIT’s McGovern Institute for Brain Research.

Lead author of the paper is Retsina Meyer, a recent MIT PhD recipient. Other authors are McGovern postdoc Anthony Burgos-Robles, graduate student Elizabeth Liu, and McGovern research scientist Susana Correia.

Stress and fear

Stress is a useful response to dangerous situations because it provokes action to escape or fight back. However, when stress is chronic, it can produce anxiety, depression and other mental illnesses.

At MIT, Goosens discovered that one brain structure that is especially critical for generating fear, the amygdala, has a special response to chronic stress. The amygdala produces large amounts of growth hormone during stress, a change that seems not to occur in other brain regions.

In the new paper, Goosens and her colleagues found that the release of the growth hormone in the amygdala is controlled by ghrelin, which is produced primarily in the stomach and travels throughout the body, including the brain.

Ghrelin levels are elevated by chronic stress. In humans, this might be produced by factors such as unemployment, bullying, or loss of a family member. Ghrelin stimulates the secretion of growth hormone from the brain; the effects of growth hormone from the pituitary gland in organs such as the liver and bones have been extensively studied. However, the role of growth hormone in the brain, particularly the amygdala, is not well known.

The researchers found that when rats were given either a drug to stimulate the ghrelin receptor or gene therapy to overexpress growth hormone over a prolonged period, they became much more susceptible to fear than normal rats. Fear was measured by training all of the rats to fear an innocuous, novel tone. While all rats learned to fear the tone, the rats with prolonged increased activity of the ghrelin receptor or overexpression of growth hormone were the most fearful, assessed by how long they froze after hearing the tone. Blocking the cell receptors that interact with ghrelin or growth hormone reduced fear to normal levels in chronically stressed rats.

When rats were exposed to chronic stress over a prolonged period, their circulating ghrelin and amygdalar growth hormone levels also went up, and fearful memories were encoded more strongly. This is similar to what the researchers believe happens in people who suffer from PTSD.

“When you have people with a history of stress who encounter a traumatic event, they are more likely to develop PTSD because that history of stress has altered something about their biology. They have an excessively strong memory of the traumatic event, and that is one of the things that drives their PTSD symptoms,” Goosens says.

New drugs, new targets

Over the last century, scientists have described the hypothalamic-pituitary-adrenal (HPA) axis, which produces adrenaline, cortisol (corticosterone in rats), and other hormones that stimulate “fight or flight” behavior. Since then, stress research has focused almost exclusively on the HPA axis.

After discovering ghrelin’s role in stress, the MIT researchers suspected that ghrelin was also linked to the HPA axis. However, they were surprised to find that when the rats’ adrenal glands — the source of corticosterone, adrenaline, and noradrenaline — were removed, the animals still became overly fearful when chronically stressed. The authors also showed that repeated ghrelin-receptor stimulation did not trigger release of HPA hormones, and that blockade of the ghrelin receptor did not blunt release of HPA stress hormones. Therefore, the ghrelin-initiated stress pathway appears to act independently of the HPA axis. “That’s important because it gives us a whole new target for stress therapies,” Goosens says.

Pharmaceutical companies have developed at least a dozen possible drug compounds that interfere with ghrelin. Many of these drugs have been found safe for humans, but have not been shown to help people lose weight. The researchers believe these drugs could offer a way to vaccinate people entering stressful situations, or even to treat people who already suffer from PTSD, because ghrelin levels remain high long after the chronic stress ends.

PTSD affects about 7.7 million American adults, including soldiers and victims of crimes, accidents, or natural disasters. About 40 to 50 percent of patients recover within five years, Meyer says, but the rest never get better.

The researchers hypothesize that the persistent elevation of ghrelin following trauma exposure could be one of the factors that maintain PTSD. “So, could you immediately reverse PTSD? Maybe not, but maybe the ghrelin could get damped down and these people could go through cognitive behavioral therapy, and over time, maybe we can reverse it,” Meyer says.

Working with researchers at Massachusetts General Hospital, Goosens’ lab is now planning to study ghrelin levels in human patients suffering from anxiety and fear disorders. They are also planning a clinical trial of a drug that blocks ghrelin to see if it can prevent relapse of depression.

The research was funded by the U.S. Army Research Office, the Defense Advanced Research Projects Agency, and the National Institute of Mental Health.

Five graduate students awarded McGovern fellowships

Anne Trafton |

This year, five graduate students have been awarded fellowships made possible by McGovern supporters.

Leah Acker, a fifth year graduate student in the labs of Ed Boyden and Robert Desimone, has been awarded a 2013-14 Friends of the McGovern Fellowship. Leah is focused on understanding the basis of neural dynamics underlying complex behaviors in primate models. She is developing extremely precise optogenetic technologies for observing neural circuits that give rise to high level cognitive functions such as attention. Leah hopes her work will lead to the development of new treatments for brain disorders.

Graduate student Yinqing Li, a member of Feng Zhang‘s lab, has been awarded a Friends of the McGovern Fellowship for his work sequencing the connectome, a comprehensive map of neural connections in the brain. Yinqing’s research has involved developing novel technologies for barcoding individual neurons with unique identifiers, and then pooling, amplifying, and preparing individual neurons for next-generation sequencing. His work has the promise to fundamentally change the way systems neuroscientists learn about the connections underlying neural circuit function.

The Mark Gorenberg ’76 Fellowship has been awarded to Leyla Isik, a fourth year graduate student studying with Tomaso Poggio, for her research into the visual system. Bridging neuroscience and computer science, Leyla uses sophisticated computer simulations and magnetoencephalography (MEG) imaging of humans to develop improved computer algorithms for object recognition. Leyla has developed a methodology that enables a machine to identity which image a human subject is looking at on the basis of his or her MEG data, and is currently performing new experiments to understand how humans recognize these images under complex viewing conditions (such as in a cluttered background, or at different positions or viewpoints). Leyla hopes to use these insights to develop a new computational model that simulates how humans develop invariant object recognition

Tatsuo Okubo, a graduate student in Michale Fee‘s lab, is this year’s recipient of the Huburt Schoemaker Fellowship. Tots’ research is focused on understanding the brain circuitry underlying the development of complex learned behaviors. Using young songbirds just learning to sing as a model, Tots is investigating the role of the premotor area HVC in the avian brain, which is analogous to Broca’s area in the human brain. Tots employs sophisticated electrophysiological recording techniques while the bird is singing to observe the process of learning at the level of individual neurons. His goal is to understand how the activity pattern in the premotor area changes during song learning, and he hopes this research will give insight into learning complex behavior in general such as language acquisition in humans.

The Janet and Sheldon (1959) Razin Fellowship has been awarded to Joshua Manning, a graduate student in John Gabrieli‘s Lab. Josh’s goal is to use neuroimaging to understand decision making, risk taking, and sense of reward in the brains of healthy people as well as individuals with psychiatric disorders. He is working with sophisticated computer models, MRI scans, and personality and cognitive data to develop a better sense of the brain basis of psychiatric illnesses. Josh hopes to advance our knowledge of the neurological root of behaviors linked to impatience and impulsivity in individuals with brain disorders such as anxiety and attention deficit hyperactivity disorder.

Early Explorations of the Visual Cortex

Anne Trafton |

On October 14, 2011, Nobel laureates David Hubel and Torsten Wiesel discussed their early explorations of the visual cortex.

Brain Scan Cover Image: Spring 2013

Anne Trafton |

A bundle of spiny apical dendrites, reconstructed from a series of ultra-thin slices of mouse cortex. Image: Daniel Berger and Sebastian Seung (MIT); based on data from Jeff Lichtman and colleagues (Harvard).

Brains on Trial with Alan Alda

Anne Trafton |

What if we could peer into the brain to determine guilt or innocence? Could advances in neuroscience help reform our criminal justice system?

On Tuesday, September 17th, the McGovern Institute hosted a discussion with a distinguished group of legal and neuroscience experts who debated these and related questions. Alan Alda moderated the panel of experts, showed clips from his 2-part PBS special, “Brains on Trial,” and engaged the audience in a Q&A session.

See below for a photo gallery of the event. All photos courtesy of Justin Knight.