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Harvard researchers among those receiving more than $150M from NIH BRAIN Initiative

Posted: 22 Nov 2017 02:11 PM PST

Harvard scientists are among dozens of researchers who will receive more than $150 million in funding over the next five years through the National Institute of Health's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative as part of an ambitious effort to better understand the inner workings of the brain.

Among those receiving funding through the program are:

  • A team of researchers led by Paola Arlotta of the Department of Stem Cell and Regenerative Biology and the Eli & Edythe Broad Institute of MIT and Harvard, and including Howard Hughes Medical Institute investigators Catherine Dulac, the Higgins Professor of Molecular and Cellular Biology, and Xiaowei Zhuang, the David B. Arnold Jr. Professor of Science. The team will take part in a $65.4 million effort to catalog the cell types in the brains of mice and determine which genes each type uses.
  • Florian Engert, professor of molecular and cellular biology; Jeff Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology and Santiago Ramon y Cajal Professor of Arts and Sciences; Haim Sompolinsky, visiting professor of molecular and cellular biology; and Sam Kunes, professor of molecular and cellular biology, will collaborate on an $18 million-plus project aimed at understanding how neural circuits generate behavior.
  • Zhuang and Dulac are also among several investigators taking part in a $65.5 million project to create a comprehensive cell-type atlas for the brains of mice.

"Before we can fully understand how our brains work, we need to understand how the parts work," said NIH Director Francis S. Collins. "Making molecular, anatomical, and functional data about brain cells available to the broad research community will speed our understanding of how cells and circuits are organized, revealing the rules of communication within the world's most complex known organ."

Catherine Dulac and Xiaowei Zhuang

Dulac and Zhuang are among the researchers working with Arlotta in an ambitious project to not only identify all the cell types in the brains of mice, but to determine what set of genes each type uses, and map their physical locations.

"In order to solve medical problems, you really need this foundational knowledge of what cell types there are, where in the brain they are, and where they connect to," Arlotta said recently. "And much of this information has been missing in the field, because we were not able, technology-wise, to gather it across the whole brain."

The hope is that by combining a catalog of different brain cell types with an atlas of their locations, researchers will ultimately gain a better understanding of how the brain develops, connects, and works — and how disease can cause those processes to go awry.

"Along my entire scientific career, I have been fascinated by the enormous cellular diversity of the nervous system," said Dulac, who is an affiliate of Harvard's Center for Brain Science. "I have studied gene expression and function of the brain one cell at a time when I was a Ph.D. student, a postdoc, and a starting junior faculty. Since then, methods of exploration of cellular diversity and single cell function in the brain have evolved tremendously and across multiple disciplines.

"These U19 grants offer a unique opportunity to work with like-minded colleagues who have developed some of the most powerful cellular, molecular, physiological, and biophysical approaches to look at brain function one cell at a time," she continued. "This is very exciting and will be highly challenging; I am very grateful to the NIH for funding this initiative and for my wonderful colleagues at Harvard and in other institutions participating in this effort."

As part of a separate grant, Zhuang will work in conjunction with researchers at the Seattle-based Allen Institute, to use high-throughput sequencing and imaging technologies developed in her lab to create the first comprehensive cell-type atlas of a mouse brain, and to characterize the molecular, anatomical and functional qualities of each.

Armed with that data, as well as other data on how various cell types combine to form neural circuits, researchers will be able to better understand the function of both healthy and diseased brains.

"We are very excited to use MERFISH, the single-cell transcriptome imaging method that we developed, to map the cell atlas of the brain," Zhuang, an affiliate of the Center for Brain Science, said. "Determining how cells are organized in our body, including the brain, is a major reason why we developed the MERFISH method. We are very glad to work on this NIH brain cell atlas project together with both colleagues at Harvard, like Catherine Dulac and Paola Arlotta, and many scientists outside Harvard."

Florian Engert and Jeff Lichtman

Understanding how the brain puts its various cell and neuron types to work is also a challenge. Kunes, Engert, Lichtman, and Sompolinsky, all of whom are affiliates of the Center for Brain Science, aim to produce a comprehensive explanation of how neural circuits generate behavior in zebrafish, as well as how the brain sorts through conflicting stimuli to make decisions and how neural circuit function is altered by problems such as stress, hunger, and loneliness.

Those processes, they said, lie at the foundations of human cognition, both in health and disease. By better understanding such basic principles, they hope that researchers might one day help guide medical interventions to repair malfunctioning neural circuits and restore the affected behaviors.

"The BRAIN Initiative, and in particular the new U19 format, have opened up opportunities for tackling fundamental questions on brain and circuit function in a quite different manner. The large scale of the award allowed us to bring together a mid-sized team of about 20 national and international scientists with a common focus on zebrafish neuroscience," Engert said. "We strongly believe that such a coordinated effort is useful because it turns competition and secrecy into collaboration and synergy.

"I'm especially excited about the fact that the U19 will allow me to now work much more closely with my three close colleagues and friends Jeff Lichtman, Haim Sompolinsky, and Josh Vogelstein [an assistant professor at Johns Hopkins School of Medicine]. Together we can do truly wonderful things that we couldn't accomplish individually, and without the U19 this wouldn't be possible. It's a transformative and very exciting opportunity."

"We are thrilled to have the opportunity to dive deeply into the structure of the nervous system of the zebrafish," Lichtman said. "This is one of the few vertebrate animals, perhaps the only one, where it is possible to get a complete map of the network connectivity and function of every single nerve cell. We are also fortunate to be part of such a skilled team of research labs all focused on the same questions."



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At Harvard, officials, students worry over a plan in Congress to tax grad student tuition support

Posted: 22 Nov 2017 11:45 AM PST

Nobody enters a Ph.D. program to earn money. Students have long known that preparing for a career in research or academia often means trading financial reward today for the chance to tackle some of the world's most pressing problems tomorrow.

Legislation now making its way through the U.S. Congress could make the financial barrier to attending graduate school much higher. A bill passed by the House of Representatives on Nov. 16 includes a set of tax hikes intended to help pay for a sweeping, $1.5 trillion tax cut that could undercut finances for students across the U.S., particularly those pursuing advanced degrees.

The plan proposes to tax those pursuing masters' and doctoral degrees by turning the tuition waivers offered by most research universities into taxable income. For many graduate students, that would have serious consequences.

In her fourth year of a bioengineering Ph.D., Blakely O'Connor designs and builds "organs-on-chips" in a lab at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). "We use cells and tissues to build models outside of the body on a micro scale, and then we can look and see how these tissues respond to drugs and how they might be disrupted in disease," said O'Connor, who hopes to continue her research and become a professor once she finishes her doctorate.

Like many such students, O'Connor is worried about how the House tax plan could affect graduate studies more broadly.

"It's really concerning to think about paying significantly more taxes when our graduate student stipends are tailored to cover exactly what we need to cover: housing, food, and living expenses in Boston," said O'Connor. "To pay thousands more dollars on top of the taxes we already pay would make the graduate student experience impossible for people who don't have savings to cover it."

The bottom line, said O'Connor, is that grad student tax obligations would likely increase under the proposed plan, and might even triple during the first couple of years of graduate study if tuition is considered taxable income. "Graduate students are really worried by the prospect of having this extra financial burden," she said. "The future of graduate studies is really uncertain."

In a recent letter to the Harvard community, Provost Alan Garber said that it remains unclear how the legislation would apply to the University, but that those seeking advanced degrees at Harvard would also "be required to report tuition support as taxable income." A tax on graduate student tuition, said Garber, would be damaging.

As part of their stipends, graduate students teach and conduct important research, helping advance knowledge across a range of disciplines. With fewer people able to afford advanced degrees, Garber and others argue that America could miss out on critical breakthroughs, undermining the nation's ability to compete in the global economy.

"Graduate students are critical to current research activities at universities. They also represent the future of research that aims to solve the greatest problems facing our nation and the world — everything from cancer to Alzheimer's disease to climate change," said Garber, who is also the Mallinckrodt Professor of Health Care Policy at Harvard Medical School.

"By making graduate education unaffordable, this short-sighted tax plan will slow progress toward groundbreaking discoveries that would otherwise improve and extend the lives of millions of Americans. And it will make it more likely that any such discoveries will be made elsewhere. At a time when other nations are increasing their investments in research and the training of scientists, this tax jeopardizes America's leadership in innovation."

Emma Dench, interim dean of Harvard's Graduate School of Arts and Sciences, agreed that the House tax plan could spell disaster for those seeking advanced degrees.

"Plain and simple, I just think it would be catastrophic for graduate education," said Dench.

Dench fears that graduate students across the country who are already barely getting by, many of whom enter graduate school laden with heavy debt from their undergraduate years, would find an added tax an obstacle too great to overcome. She also worries that such a tax would shrink the talent pool and diversity of graduate students in the U.S., discouraging those lacking financial means from even applying to graduate school.

"The students lose out; the fields of scholarship lose out. It's a devastating lost opportunity all around," she said.

Humanities research that carries wide-ranging implications could be curtailed by such a tax, including work in the medical humanities, which takes a "holistic and compassionate approach to care," as well as research by humanists addressing climate change, Dench said.

"Then there is also just the debt to understanding the human condition. That would take a terrible toll."

Over the past week, graduate students across Harvard have flooded Dench's email with their concerns. "My inbox," she said "is filled with distress."

By narrowing the field of potential graduate degree candidates, such a tax could do significant harm to the U.S. economy, analysts say. They argue that fewer graduate students and a less-educated workforce would put the country at a severe competitive disadvantage.

Reducing support for higher education in order to cut corporate tax rates is the wrong long-term strategy for growing America's economy, said Jason Furman, who was chairman of the Council of Economic Advisers during the Obama administration.

Making graduate students responsible for thousands of dollars in additional taxes, coupled with the prospect of placing a tax on the endowments of large universities, would "reduce the resources those universities have for financial support and would result in fewer people going to graduate school, where critical knowledge is generated," said Furman, professor of the practice of economic policy at Harvard Kennedy School.

That knowledge, he added, "isn't owned by anyone, but spills over and benefits society, in areas such as health care or the economy."

Furman noted that a main expressed goal of the House tax plan is to make America more globally competitive by bringing corporate tax rates in line with those of other nations. But that calculation, he said, ignores one of the U.S. economy's biggest strengths.

"If you ask why most of the major tech companies are in the United States, it's because of our educational system. Biomedicine, artificial intelligence, all of these sectors where the United States is leading the world are because of our educational system. And to think that competitiveness is all about your corporate tax rate and not your economic institutions as a whole, and particularly education, is really mistaken."

Officials at Harvard have joined experts nationally in expressing concern over the proposed tax, including Harvard President Drew Faust, who has made regular visits to Washington during her presidency to advocate for policies to safeguard and improve higher education. Faust said she sees several troubling things in the House tax plan.

"These measures have the potential to seriously damage American higher education as well as individuals who live, work, and learn at colleges and universities across the country. I am deeply concerned about the ways in which these measures threaten to undermine innovation and discovery, and deter people from pursuing their educational goals," she said. "I will continue to work with my colleagues in higher education to make these concerns known to policymakers in Washington."

In addition to the tax on graduate students, the House plan has a provision to tax the charitable endowment earnings of private universities that have endowments larger than $250,000 per student. Many higher-education officials argue that an endowment tax reflects a fundamental misunderstanding of how such endowments work, and that it could threaten critical financial aid programs and research funding.

"On top of the tax on tuition remission, the proposed tax on Harvard's endowment would also affect the number of students whom Harvard can admit. The number of students who are admitted would likely go down, especially in departments with budgets heavily influenced by the endowment," said O'Connor. "So even if we can avoid income taxes on graduate tuition, the proposed tax on the endowment could greatly affect the graduate student experience here at Harvard."

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Native American language preservationist discusses his work on ‘Heard at Harvard’

Posted: 22 Nov 2017 11:00 AM PST

Marcus Briggs-Cloud, M.T.S. '10, has dedicated his life to revitalizing his ancestral tongue and the cultural identity it sustains. An indigenous Maskoke, for more than a decade he has been teaching his native language to college and high school students and preverbal infants, including his own children, to whom he has never spoken a word of English. He returned to the Divinity School in October to participate in the biennial Native American Speaker Series. For part two of a two-part series of discussions with Native American language preservationists, Briggs-Cloud sat down with the Gazette to discuss his work since leaving Cambridge.

We speak, therefore we are

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