RNA dynamics deconstructed

Technique offers detailed view of how RNA levels change

RNA plays a critical role in directing the creation of proteins, but there is more to the life of an RNA molecule than simply carrying DNA's message. One can imagine that an RNA molecule is born, matures, and eventually, meets its demise. Researchers at the Broad have developed an approach that offers many windows into the lifecycle of these essential molecules and will enable other scientists to investigate what happens when something in a cell goes wrong. They describe their approach, which offers high resolution and a comprehensive scope, in a Nature Biotechnology article published online on April 24.

"People are discovering more and more how the RNA lifecycle is at the heart of problems we see in disease, but we actually understand a lot less about it than we understand about many other cellular processes," said Aviv Regev, a core faculty member of the Broad Institute and a co-senior author on the paper.

Regev and her colleagues have developed a method that allows them to tease apart the different stages of this lifecycle by measuring how much messenger RNA is produced and how much is degraded. The balance of these two processes contributes to the changes seen in RNA levels in a cell over time, much the way that birth and death rates contribute to a country's total population.

RNA levels are dynamic – they change in response to certain stimuli. For this study, the researchers examined dendritic cells, which are involved in the body's immune response, as a model. They exposed these cells to a stimulus that resembled a pathogen and then looked at RNA changes before and after exposure.

"We wanted to understand how cells regulate RNA levels, and if regulation happens at the step of producing the molecule, degrading the molecule, or processing it," said Michal Rabani, first author of the paper and an MIT graduate student at the Broad. "Each of these steps can affect the level of active RNA molecules in cells. If you want to understand what happens when things go wrong, you have to understand how things work when they work as they should."

The researchers' approach allows them to look at a specific cell type and see changes in the expression of all genes. This combination of breadth and specificity offers a systematic view of how RNA changes over time. "If we want to look at specific neurons in the brain or a specific cell that's lying between other kinds of cells in the lung, this technique allows us to zoom in on one process in one cell among a billion other cells. This is the case in many diseases, a short circuit in one specific cell type, and now we have a great tool to find it," said Ido Amit, a co-senior author of the paper and a scientist at the Broad.

The scientists harnessed an existing technique to trace the fate of newly produced RNA and paired it with a new sequencing-based technology that counts molecules of mRNA. The results also gave the researchers a view of some of the in-between steps, during which mRNA is edited or processed – an unexpected but serendipitous finding. "That's the beauty of sequencing: it has a very extensive view so it shows you things you didn't expect to see," said Regev.

A key aspect of the approach is that the researchers were able to take "snapshots" of RNA levels over very short time intervals. Strung together, these snapshots reveal not only how the amount of RNA changes, but also the short-lived, intermediate phases of the RNA lifecycle that are otherwise impossible to detect. "This allows us many windows into the world of RNA," said Amit.

One critical application of the new method is in following up on leads from disease studies, such as mutated genes in cancer or other diseases that impact the RNA lifecycle. "In the past, you would know that there's a mutation and there's even a suspicion of what the gene does, but it would have been extraordinarily hard to see the effect of the mutation on these types of processes in the cell," said Regev, who is also an assistant professor at MIT and an early career scientist at the Howard Hughes Medical Institute. The researchers hope that their newly developed technique will enable others to gain deep insights into how gene mutations disrupt RNA levels, and in turn, what proteins are made.

"We're decomposing these RNA levels, breaking them down into each separate step, so that we can understand what happens at each of these steps and how they interact with each other to produce the final read out," said Rabani. "It's a very complex system, but understanding it could eventually help us understand what goes wrong when things don't work."

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This work was supported by the Richard Merkin Foundation for Stem Cell Research at the Broad Institute through a gift that Regev describes as essential for the project's success.

Paper cited:

Rabani M et al. Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells. Nature Biotechnology. April 24, 2011. DOI: 10.1038/nbt.1861

About the Broad Institute of Harvard and MIT

The Eli and Edythe L. Broad Institute of Harvard and MIT was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods and data openly to the entire scientific community.

Founded by MIT, Harvard and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://www.broadinstitute.org.

About the Richard Merkin Foundation for Stem Cell Research at the Broad Institute

The Richard Merkin Foundation for Stem Cell Research at the Broad Institute seeks to fund Broad Institute-affiliated scientists to develop a novel and comprehensive "toolbox" of experimental methods and computational algorithms and to apply those tools to understand cellular circuitry in stem cells, with the goal of being able to manipulate those circuits for both biological knowledge and medical applications.

Contact: Nicole Davis
ndavis@broadinstitute.org
617-714-7152
Broad Institute of MIT and Harvard

Massachusetts Institute of Technology researchers offer glimpse of rare mutant cells

Imaging system may help understand origins of cancer

MIT biological engineers have developed a new imaging system that allows them to see cells that have undergone a specific mutation.

The work, which could help scientists understand how precancerous mutations arise, marks the first time researchers have been able to pinpoint the number and location of mutant cells—cells with a particular mutation—in intact tissue. In this case, the researchers worked with mouse pancreatic cells.

"Understanding where mutations come from is fundamental to understanding the origins of cancer," said Bevin Engelward, associate professor of biological engineering and member of MIT's Center for Environmental Health Sciences, and an author of a paper on the work appearing in this week's online edition of the Proceedings of the National Academy of Science.

Peter So, professor of biological and mechanical engineering, Engelward and members of their laboratories developed technologies that made it possible to detect clusters of cells that appeared to be descended from the same progenitor cell.

Unexpectedly, more than 90 percent of the cells harboring mutations were within clusters. That offers evidence that the majority of mutations are inherited from another cell, rather than arising spontaneously in individual cells.

Since the type of mutation being studied (in this case a recombination event) occurs at a rate on par with other types of mutations, "it is as if we are peering in at the very general process of mutation formation, persistence and clonal expansion," said Engelward.

"We think this raises the possibility that mutations resulting from cell division are a tremendous factor in increasing the mutagenic load," she said.

The higher the mutagenic load, the more likely it is that cancer will develop.

Engelward and So started working together several years ago after a faculty retreat for MIT's newly formed Biological Engineering Division. So was developing a new type of microscopy, known as two-photon imaging, and the researchers wondered whether it could be used to locate and image rare types of cells.

The team genetically engineered a strain of mice in which DNA would fluoresce if a mutation occurred in a particular sequence. That allowed them to use So's newly developed high-resolution, high-throughput microscopy technique to detect individual cells that carry the mutation.

"The problem drove the development of a new imaging technology, which now can be used for lots of things," said Engelward.

Lead author of the paper is Dominika Wiktor-Brown, a postdoctoral associate in biological engineering. Other authors of the paper are Hyuk-Sang Kwon, a research affiliate in the Department of Mechanical Engineering, and Yoon Sung Nam, a graduate student in biological engineering.

The work was truly a team effort between many people with very different areas of expertise, said Engelward. "The Department of Biological Engineering and the Center for Environmental Health Sciences are key in helping to bridge people across disciplines," she said.

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The research was funded by the National Institutes of Health, the Department of Energy and the Singapore-MIT Alliance.

MIT instrument studies edge of sun's bubble

Spacecraft gives data on space beyond sun's influence

Image / NASA/JPL

The scale of the heliosphere and nearby galactic neighborhood. The solar system and its nearby galactic neighborhood are illustrated here on a logarithmic scale extending (from <>

The Voyager 1 and 2 spacecraft have traveled beyond the edges of the bubble in space where the sun's constant outward wind of particles and radiation slams into the interstellar medium that pervades our galaxy. The first scientific reports on what the Voyagers found there appears this week in the journal Nature.

The deep-space probes, which were designed mainly to study the outer planets Jupiter, Saturn, Uranus and Neptune, have now traveled more than 8 billion miles away from the Earth. Voyager 1 is now more than 94 Astronomical Units away (one AU is the average distance from the Earth to the sun, or 93 million miles), and Voyager 2 is more than 84 AU. Because they are leaving the solar system on paths that are about 45 degrees apart, the data reveals details about the shape of the bubble created by the solar wind. The fact that they crossed the edge of the solar outflow--a region called the boundary shock--at different distances out from the sun proved that this bubble is squashed rather than being a symmetrical sphere.

Some of the data that revealed this boundary region comes from a set of magnetic field sensors developed and built at MIT back in the 1970s, based on an earlier MIT instrument sent on Explorer 1 in 1961. John Richardson, Principal Research Scientist at MIT's Kavli Institute for Astrophysics and Space Science, is a co-author of the two Nature papers, and John Belcher, professor of physics at MIT and former principal investigator for the Voyager Plasma Science instrument, is a co-author of one of them.

"We have never made direct measurements in the interstellar medium, the material between the stars," Belcher says, "because the sun's supersonically expanding atmosphere blows a bubble in the local interstellar medium whose radius is 100 times the distance from the sun to the Earth."

"It's starting to feel the interstellar wind," Richardson says of the fast-receding spacecraft, which is already more than three times as far from the sun as the solar system's outermost planets. "The interstellar wind is coming at us at 26 km per second," he says.

Sometime about a decade from now, Belcher says, Voyager 2 "will be through the shocked solar wind and into the interstellar medium proper. This is the material out of which the sun condensed, which has never been explored before."

Nobody knows much about that interstellar medium, such as what the density of hydrogen atoms is in that incredibly tenuous vacuum. "We will be able to deduce that better" once Voyager reaches it, Richardson says. "We'll also get a first look at cosmic rays that haven't been influenced by the sun's magnetic field, once we get outside," and thus learn more about the origins of these extremely fast-moving particles, he says. "That's one of our major scientific goals."

On a personal note, Belcher said that the creators of the MIT plasma instrument all wrote their names inside it before it was sent to be attached to the spacecraft. "My father had a 7th grade education, my generation was the first in the family to go to college," he says, "and my name is on a spaceship that will eventually reach the stars and probably last longer than the Earth itself!"

An earlier report on what Voyager 2 found was presented at a scientific meeting last December.

The work was funded by NASA.

Team unveils 'parts list' of cell powerhouse

Image / Bang Wong, Broad Institute, from a Joint Center for Structural Genomics image

Individual proteins converge to form the distinctive shape of mitochondria.

Imagine trying to figure out how your car's power train works from just a few of its myriad components: It would be nearly impossible. Scientists have long faced a similar challenge in understanding cells' tiny powerhouses -- called mitochondria -- from scant knowledge of their molecular parts.

Now, an international team of researchers has created the most comprehensive "parts list" to date for mitochondria, a compendium that includes nearly 1,100 proteins. By mining this critical resource, the researchers have already gained deep insights into the biological roles and evolutionary histories of several key proteins. In addition, this careful cataloging has identified a mutation in a novel protein-coding gene as the cause behind one devastating mitochondrial disease. A full description of the work appears in the July 11 print edition of the journal Cell.

"For years, a fundamental question in cell biology has gone largely unanswered -- what proteins function in mitochondria?" said Vamsi Mootha, an associate member at the Broad Institute of MIT and Harvard and a Harvard Medical School assistant professor at Massachusetts General Hospital, who led the study. "By creating a comprehensive list, we now have a valuable resource that has already helped enhance our understanding of mitochondrial biology and disease."

Mitochondria, found within the cells of all eukaryotes from yeast to humans, are miniaturized organs ("organelles") well known for their role in providing cellular energy. They have also been implicated in a wide range of normal and disease processes, including diabetes.

Although mitochondria have their own genome -- a vestige from their days as free-living bacteria -- the vast majority of the critical mitochondrial proteins are derived not from their genome, but rather from the nuclear genome. However, even with the wealth of genome sequence data now available, scientists have struggled to identify which genes encode the roughly 1,200 proteins that make up a functional mitochondrion.

Researchers from the Broad Institute, Harvard Medical School, and Massachusetts General Hospital worked together to address this problem.

"The technologies and analytical methods for measuring proteins on a large scale are really transforming what we can learn about human biology," said Steve Carr, director of the Proteomics Platform at the Broad Institute and a co-author of the Cell paper. "By applying them to mitochondria isolated from fourteen different mouse tissues, we've completed one of the most comprehensive proteomic analyses of any organelle to date."

As a result of their analyses, the researchers identified a total of 1,098 mitochondrial proteins to form a compendium they have named "MitoCarta," and which is available to the entire scientific community. Notably, about one-third of this inventory has not been previously linked to the organelle.

To shed light on the functions of the newly uncovered mitochondrial proteins, the researchers compared the proteins' corresponding gene sequences across hundreds of species, from humans and fish to fungi and bacteria. "Proteins with similar roles often share similar histories, meaning they're gained or lost together during evolution," said Mootha. "We decided to use this tendency to our advantage to decipher how some mitochondrial proteins work."

By examining the organelle's proteins through this evolutionary lens, the researchers uncovered a striking pattern. A group of key mitochondrial proteins, known to be absent in yeast but otherwise present among eukaryotes, are actually missing from several other single-celled species. In organisms that have them, including humans and other mammals, these proteins contribute to a boot-shaped, multi-protein structure, which forms the gateway to a critical step in the energy-generation process. By virtue of these proteins' shared -- and unusual -- past, Mootha and his colleagues were able to identify several additional proteins that are also associated with this crucial mitochondrial structure, known as complex 1.

In addition to offering insights into mitochondrial biology, these discoveries also paved the way for a breakthrough in understanding mitochondrial disease. For decades, doctors have diagnosed patients with deficiencies in complex 1 function. These disorders affect about one in 5,000 newborns, are genetic in origin, and are lethal in the first few years of life. Yet for many cases a culprit gene cannot be found. However, thanks to MitoCarta and its corresponding evolutionary analyses, the researchers and their collaborators at the University of Melbourne and Royal Children's Hospital in Australia identified a mutation in a novel gene, called C8orf38, as one cause of complex 1 disease.

"Our finding underscores the power of this protein catalogue to open new vistas on disease," said Mootha. "It promises to shed light not only on rare metabolic diseases, but common diseases as well."

This work was supported by the National Institute of General Medical Sciences.

MIT expert: Don't count on long-term success in climate poli

Says policy-making requires ambitious short-term goals

Long-term climate change policy in the United States and abroad is likely to change very slowly, warns an MIT professor who says the lack of future flexibility argues for stronger short-term goals to reduce carbon emissions.

In a study in the current issue of Decision Analysis, a journal of the Institute for Operations Research and the Management Sciences, Assistant Professor Mort Webster of MIT's Engineering Systems Division tackles the complex problem of global climate change policy with a new approach.

Specifically, Webster's analysis incorporates the theory of "path dependency." In its most basic form, the theory holds that how something evolves in the future depends heavily on the path it was on in the past.

Webster says that because policy-making for climate change involves sequences of decisions over very long time periods, it is possible to reduce uncertainty and revise decisions along the way. But political systems can exhibit path dependency, a force that makes large policy shifts in the future difficult and rare, so most future decisions may only offer relatively small, incremental changes.

"Although staging climate change policy decisions over time would seem to make sense, the tendency of U.S. and international policy to change extremely slowly requires front-loading the painful decisions," Webster says, arguing that greater near-term emissions reductions are needed as a hedge against long-term catastrophe.

Webster challenges the Bush administration, which has cited uncertainty about future climate change among the reasons that it calls for the postponement of stricter mandated emissions reductions until the next decade.

The White House approach raises central questions for near-term climate policy, both in the United States and abroad, he writes: whether or not regulations of greenhouse gas emissions can be delayed, and whether some level of mitigating effort is required at once. Countering those who say the dust should settle before committing to big decisions, he points out that when a decision will be irreversible - as is likely the case in climate policy - delaying the decision is probably not the best option, according to research in decision analysis.

Decision-making in public policy, he writes, is complicated by the reluctance of leaders to reverse course after they have made important policy choices.

"A large-scale international policy issue such as climate change is especially vulnerable to path dependencies. If significant global emissions reductions are required in the long-run, this will be an extremely difficult problem to coordinate across nations," he writes.

Climate policy optimization models typically assume that some fraction of baseline emissions can be reduced in each period, ranging from none to nearly 100 percent, he notes. But, he notes, the range of reductions considered in any period is independent of any choices made in previous periods.

"The question posed in this study is: Does accounting for path dependency in political systems change the first-period (today) optimal choice from a sequential decision model of climate policy?" he writes. " If it does, then this would argue for a more aggressive hedging strategy with greater emissions reductions for near-term climate policy. This action would allow for greater flexibility if significant reductions are required later in the century."

Note: This text was adapted from a news release originally issued by the Institute for Operations Research and the Management Sciences.

A hands-on approach to Third World aid

Month-long IDDS workshop targets development through design

About 60 people from 20 nations will descend on the MIT campus next week to begin an intensive month-long process of creating technological solutions for the needs of people in the world's developing nations. The goal of the program is to develop simple, inexpensive devices that in some cases can be produced locally and make a real difference for people and communities.

This year's International Development Design Summit, which begins Monday, July 14, and runs through Aug. 8, is the second incarnation of the workshop. The event, which was the brainchild of MIT Senior Lecturer and D-Lab founder Amy Smith, a past winner of the MacArthur "genius" grant, is co-sponsored by MIT, Olin College, Caltech and Cooper Perkins, a local design firm.

As they did last year, participants will split into about 10 teams that will each spend the four weeks developing some piece of technology that in some cases could be built using local tools and materials and meet significant needs of local people in the developing world -- especially in small, rural communities. In many cases, building, selling and operating these devices could also become a source of revenue and jobs at the local level.

This year's IDDS organizing team includes several of the participants from last year's inaugural conference. "It is wonderful to have them back on campus and hear what they have been up to since last year's summit," says Smith. "In many cases, IDDS really changed the direction of their lives." The event is intended as a collaboration between people of a wide range of backgrounds: students, faculty, mechanics, social workers, doctors, carpenters, farmers, and professors from around the world, who will join forces to build technologies that could improve the quality of life in the developing world.

Several of the technologies that were developed during last year's summit, including transparent containers for transporting and sterilizing water, devices for reducing the smoke from cooking fires, and low-cost refrigeration systems, are on their way to being produced in various countries around the world, Smith says.

As Niall Walsh, a student from Trinity College Dublin who is helping to organize the event, describes it in his blog in which he is tracking the whole progress of the conference, its purpose is to "challenge convention by creating physical solutions. A team … from around the world will work together to attempt to create, within a few weeks, technologies that could change lives."

The event is partly funded by the Rockefeller Foundation; the National Collegiate Inventors and Innovators Alliance; Continuum, a local design firm; and by MIT's Public Service Center and International Development Initiative.

Partnership between test reactors to support nuclear energy research

The Advanced Test Reactor National Scientific User Facility (ATR NSUF), centered at Idaho National Laboratory (INL), and the Massachusetts Institute of Technology Reactor (MITR) have announced a partnership designed to increase user access to national reactor irradiation and testing capability.

NSUF Scientific Director Todd Allen said that with the ATR NSUF fall 2008 solicitation for experiments, the MITR will offer a portion of its test capability to the NSUF experimenters.

"This arrangement increases opportunities for reactor testing and provides the NSUF greater flexibility to respond to user needs," Allen said.

NSUF test space at both reactors is made available at no cost to external users whose projects are selected via a peer-review process. This partnership with MITR is the first in an expected series of national partnerships designed to enhance the NSUF infrastructure and capability.

In April 2007, the U.S. Department of Energy designated INL's Advanced Test Reactor as a National Scientific User Facility. The designation will help assert U.S. leadership in nuclear science and technology and will attract new users--universities, laboratories and industry--to conduct research at the ATR. This facility will support basic and applied nuclear research and development (R&D), furthering President Bush's Advanced Energy Initiative, which will advance the nation's energy security needs.

The MITR is a 5-megawatt research reactor owned and operated by MIT. The MITR has carried out interdisciplinary research in advanced materials and fuel testing for next-generation nuclear systems. One of the many capabilities of the MITR involves the use of in-core loops and the ability to reach temperatures of up to 1,600 degrees centigrade. This allows researchers to replicate nuclear power reactor conditions to study the behavior of advanced materials and fuel designs for next-generation nuclear reactors. The MITR contains a wide range of irradiation facilities that are utilized for various nuclear applications such as neutron transmutation doping, neutron science and neutron capture therapy.

"This partnership represents a great opportunity to take advantage of unique national resources to help address the nation's energy challenges," said MIT Vice President for Research Claude Canizares.

Study points to dietary cocktail for Alzheimer's

Supplement improves memory, learning in gerbils

A dietary cocktail that includes a type of omega-3 fatty acid can improve memory and learning in gerbils, according to the latest study from MIT researchers that points to a possible beverage-based treatment for Alzheimer's and other brain diseases.

The combination of supplements, which contains three compounds normally found in the bloodstream, is now being tested in Alzheimer's patients. The cocktail has previously been shown to promote growth of new brain connections in rodents.

"It may be possible to use this treatment to partially restore brain function in people with diseases that decrease the number of brain neurons, including, for example, Alzheimer's disease, Parkinson's, strokes and brain injuries. Of course, such speculations have to be tested in double-blind, placebo-controlled clinical trials," said Richard Wurtman, Cecil H. Green Distinguished Professor of Neuropharmacology and senior author of a paper on the new work.

Such trials are now underway in Europe. A paper describing preliminary results has been submitted to the Alzheimer's Association International Conference on Alzheimer's Disease, to be held in Chicago July 26-31.

The new findings in gerbils appeared in the July 7 online edition of the Journal of FASEB (Federation of American Societies of Experimental Biology).

The researchers found that normal gerbils treated with the mixture--a combination of DHA (a type of omega-3 fatty acid), uridine and choline--performed significantly better on learning and memory tests than untreated gerbils.

Wurtman developed the treatment as a new approach to tackling Alzheimer's--restoring the synapses, or connections between brain cells, that leads to cognitive decline in Alzheimer's patients.

Synapses, where information is passed between neurons, play a critical role in learning and memory. Wurtman's laboratory has previously shown that the cocktail treatment improves those functions in rats with cognitive impairments.

The three dietary supplements under investigation are precursors to the fatty molecules that make up cell membranes, including the membranes of brain cells, which form synapses.

In the FASEB study, Wurtman and his colleagues found that gerbils that received all three supplements had up to 70 percent more phosphatides (a type of molecule that forms cell membranes) than control mice, suggesting that new synapses are forming.

"The improvements in cognition observed in normal gerbils in this study and in rats with impaired cognition, in a previous study, correlate perfectly with the evidence of increased brain synapses, as shown biochemically and anatomically," said Wurtman. "This suggests that treating the animals with the experimental mixture affects behavior by increasing the number of synapses in important brain regions.

Some of the gerbils in the studies received all three compounds and some received only two. The improvements in apparent synapse growth and cognitive ability were greatest in the rats given all three.

Omega-3 fatty acids are not produced in the body but are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Choline can be synthesized in the body and obtained through the diet; it is found in meats, nuts and eggs. Uridine cannot be obtained from food sources, but is a component of human breast milk and can be produced in the body.

Lead author of the FASEB paper is Sarah Holguin, a recent MIT PhD recipient. Other authors are MIT undergraduates Joseph Martinez and Camille Chow.

The research was funded by the National Institutes of Health and the CBSMCT.

Jack Howard, chemical engineering professor emeritus, 70

Jack Howard, a professor emeritus in the Department of Chemical Engineering, died on July 7 after a battle with brain cancer. He was 70.

Howard received a BS in 1960 and an MS in 1961 from the University of Kentucky as well as a PhD in 1965 from Pennsylvania State University. After earning his doctorate, Howard came to MIT, where he held positions as assistant, associate and full professor in the Department of Chemical Engineering and served as the department's executive officer from 1979 to 1981.

He was named the first holder of the Hoyt C. Hottel Chair of Chemical Engineering in 1995; appointed director for MIT's Center for Airborne Organics in 1996; and became a professor emeritus in 2002.

Howard was a world-renowned expert in the manufacture of nanostructured carbon materials. His research focused on high temperature chemistry, especially mechanisms and kinetics of reactions in combustion. He was the author or co-author of more than 200 scientific papers and holds 15 patents for his work.

Klavs Jensen, Department of Chemical Engineering head, noted how Howard had "made seminal contributions to many challenging research areas, including formation and oxidation polycyclic aromatic hydrocarbons, fullerenes and soot in flames as well as pyrolysis, gasification and combustion of coal, biomass and solid waste. Jack's expertise with these important issues at the forefront of energy challenges facing the world will be deeply missed."

Howard received numerous awards during his career at MIT, including being named to the University of Kentucky's Engineering Hall of Distinction. He won the Bernard Lewis Gold Medal from the Combustion Institute in 1992 and the Henry H. Storch Award from the American Chemical Society in 1983.

He also held several posts in various professional societies, serving as co-chairman of the Energy Research Committee of the American Institute of Chemical Engineers from 1975-1980.

"We will all miss Jack for his deep technical knowledge and his gentle, firm advice to students and faculty alike," Jensen said.

He is survived by his wife, the former Carolyn Butler, of Winchester, Mass., and their two children, Courtenay and Jonathan. The family has maintained a blog about Professor Howard's battle at http://howardupdates.blogspot.com/

A memorial service will be held on July 16, 2008 at 10:30 a.m. at Park St. Church in downtown Boston.

Experts describe promise of nanotech for cancer detection, more

Speakers from MIT and other institutions described the promise of nanotechnology to help diagnose, treat and monitor cancer at the annual symposium hosted by the David H. Koch Institute for Integrative Cancer Research at MIT on Friday, June 27.

More than 1,100 people attended the symposium, titled "Nanotechnology and Cancer: The Power of Small Science."

Institute Professor Robert Langer, a pioneer in nanotechnology, described new techniques that researchers in his lab are using to create delivery systems for gene therapy and RNA interference. They have developed new ways to quickly synthesize a vast array of polymers that can be modified for optimal ability to deliver their payload, whether it's DNA, RNA or a drug.

"Small changes in chemistry can make huge changes in what you get," said Langer, who is also a member of the Koch Institute. "You can find very different properties and pick out polymers that do different things."

Langer and Sangeeta Bhatia, professor of electrical engineering and health sciences and technology and a member of the Koch Institute, talked about the prospect of building nanodevices that diagnose tumors, deliver drugs, and monitor the progress of treatment, all in one device.

Paula Hammond, the Bayer Professor of Chemical Engineering at MIT and Koch Institute member, described the polymers that her lab is developing to deliver cancer drugs directly to tumor cells. She uses self-assembling polymers with specific molecules attached that allow the nanoparticles to find and bind to tumor cells.

"We've been able to design these systems so they can act as very specific targeting vehicles for drug delivery," said Hammond.

Other speakers included Ralph Weissleder, director of the Center for Systems Biology at Massachusetts General Hospital, who described several types of nanoparticles his group is developing to detect cancer in its early stages. Weissleder and Langer are principal investigators of the MIT-Harvard Center of Cancer Nanotechnology Excellence.

This is the first cancer symposium held since the MIT Center for Cancer Research officially became the David H. Koch Institute for Integrative Cancer Research. The institute will be located in a new building now under construction at the corner of Main and Ames streets.

The institute will house both cancer biologists and engineers, who will work together to find new ways to detect, treat and prevent cancer.

"I'm convinced that the Koch Institute, in both the design of the building and its organization, will help define and accelerate a whole new era in cancer research," said MIT President Susan Hockfield, who opened Friday's symposium.

MIT reports finer lines for microchips: Advance could lead to next-generation computer chips, solar cells, more

MIT researchers have achieved a significant advance in nanoscale lithographic technology, used in the manufacture of computer chips and other electronic devices, to make finer patterns of lines over larger areas than have been possible with other methods.

Their new technique could pave the way for next-generation computer memory and integrated-circuit chips, as well as advanced solar cells and other devices.

The team has created lines about 25 nanometers (billionths of a meter) wide separated by 25 nm spaces. For comparison, the most advanced commercially available computer chips today have a minimum feature size of 65 nm. Intel recently announced that it will start manufacturing at the 32 nm minimum line-width scale in 2009, and the industry roadmap calls for 25 nm features in the 2013-2015 time frame.

The MIT technique could also be economically attractive because it works without the chemically amplified resists, immersion lithography techniques and expensive lithography tools that are widely considered essential to work at this scale with optical lithography. Periodic patterns at the nanoscale, while having many important scientific and commercial applications, are notoriously difficult to produce with low cost and high yield. The new method could make possible the commercialization of many new nanotechnology inventions that have languished in laboratories due to the lack of a viable manufacturing method.

The MIT team includes Mark Schattenburg and Ralf Heilmann of the MIT Kavli Institute of Astrophysics and Space Research and graduate students Chih-Hao Chang and Yong Zhao of the Department of Mechanical Engineering. Their results have been accepted for publication in the journal Optics Letters and were recently presented at the 52nd International Conference on Electron, Ion and Photon Beam Technology and Nanofabrication in Portland, Ore.

Schattenburg and colleagues used a technique known as interference lithography (IL) to generate the patterns, but they did so using a tool called the nanoruler--built by MIT graduate students--that is designed to perform a particularly high precision variant of IL called scanning-beam interference lithography, or SBIL. This recently developed technique uses 100 MHz sound waves, controlled by custom high-speed electronics, to diffract and frequency-shift the laser light, resulting in rapid patterning of large areas with unprecedented control over feature geometry.

While IL has been around for a long time, the SBIL technique has enabled, for the first time, the precise and repeatable pattern registration and overlay over large areas, thanks to a new high-precision phase detection algorithm developed by Zhao and a novel image reversal process developed by Chang.

According to Schattenburg, "What we're finding is that control of the lithographic imaging process is no longer the limiting step. Material issues such as line sidewall roughness are now a major barrier to still-finer length scales. However, there are several new technologies on the horizon that have the potential for alleviating these problems. These results demonstrate that there's still a lot of room left for scale shrinkage in optical lithography. We don't see any insurmountable roadblocks just yet."

The MIT team performed the research in the Space Nanotechnology Laboratory of the MIT Kavli Institute of Astrophysics and Space Research, with financial support from NASA and NSF.

Massachusetts Institute of Technology (MIT) opens new 'window' on solar energy

Cost effective devices expected on market soon

CAMBRDGE, Mass. -- Imagine windows that not only provide a clear view and illuminate rooms, but also use sunlight to efficiently help power the building they are part of. MIT engineers report a new approach to harnessing the sun's energy that could allow just that.

The work, to be reported in the July 11 issue of Science, involves the creation of a novel "solar concentrator." "Light is collected over a large area [like a window] and gathered, or concentrated, at the edges," explains Marc A. Baldo, leader of the work and the Esther and Harold E. Edgerton Career Development Associate Professor of Electrical Engineering.

As a result, rather than covering a roof with expensive solar cells (the semiconductor devices that transform sunlight into electricity), the cells only need to be around the edges of a flat glass panel. In addition, the focused light increases the electrical power obtained from each solar cell "by a factor of over 40," Baldo says.

Because the system is simple to manufacture, the team believes that it could be implemented within three years—even added onto existing solar-panel systems to increase their efficiency by 50 percent for minimal additional cost. That, in turn, would substantially reduce the cost of solar electricity.

In addition to Baldo, the researchers involved are Michael Currie, Jon Mapel, and Timothy Heidel, all graduate students in the Department of Electrical Engineering and Computer Science, and Shalom Goffri, a postdoctoral associate in MIT's Research Laboratory of Electronics.

"Professor Baldo's project utilizes innovative design to achieve superior solar conversion without optical tracking," says Dr. Aravinda Kini, program manager in the Office of Basic Energy Sciences in the U.S. Department of Energy's Office of Science, a sponsor of the work. "This accomplishment demonstrates the critical importance of innovative basic research in bringing about revolutionary advances in solar energy utilization in a cost-effective manner."

Solar concentrators in use today "track the sun to generate high optical intensities, often by using large mobile mirrors that are expensive to deploy and maintain," Baldo and colleagues write in Science. Further, "solar cells at the focal point of the mirrors must be cooled, and the entire assembly wastes space around the perimeter to avoid shadowing neighboring concentrators."

The MIT solar concentrator involves a mixture of two or more dyes that is essentially painted onto a pane of glass or plastic. The dyes work together to absorb light across a range of wavelengths, which is then re-emitted at a different wavelength and transported across the pane to waiting solar cells at the edges.

In the 1970s, similar solar concentrators were developed by impregnating dyes in plastic. But the idea was abandoned because, among other things, not enough of the collected light could reach the edges of the concentrator. Much of it was lost en route.

The MIT engineers, experts in optical techniques developed for lasers and organic light-emitting diodes, realized that perhaps those same advances could be applied to solar concentrators. The result? A mixture of dyes in specific ratios, applied only to the surface of the glass, that allows some level of control over light absorption and emission. "We made it so the light can travel a much longer distance," Mapel says. "We were able to substantially reduce light transport losses, resulting in a tenfold increase in the amount of power converted by the solar cells."

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This work was also supported by the National Science Foundation. Baldo is also affiliated with MIT's Research Laboratory of Electronics, Microsystems Technology Laboratories, and Institute for Soldier Nanotechnologies.

Mapel, Currie and Goffri are starting a company, Covalent Solar, to develop and commercialize the new technology. Earlier this year Covalent Solar won two prizes in the MIT $100K Entrepreneurship Competition. The company placed first in the Energy category ($20,000) and won the Audience Judging Award ($10,000), voted on by all who attended the awards.

Written by Elizabeth Thomson, MIT News Office

Photos available upon request

Broad Institute of MIT and Harvard Researchers unveil near-complete protein catalog for mitochondria

Work flows from advanced large-scale methods for measuring proteins; inventory includes nearly 300 novel proteins, highlights basis of rare metabolic disease

Imagine trying to figure out how your car's power train works from just a few of its myriad components: It would be nearly impossible. Scientists have long faced a similar challenge in understanding cells' tiny powerhouses — called "mitochondria" — from scant knowledge of their molecular parts.

Now, an international team of researchers has created the most comprehensive "parts list" to date for mitochondria, a compendium that includes nearly 1,100 proteins. By mining this critical resource, the researchers have already gained deep insights into the biological roles and evolutionary histories of several key proteins. In addition, this careful cataloging has identified a mutation in a novel protein-coding gene as the cause behind one devastating mitochondrial disease. A full description of the work appears in the July 11 print edition of the journal Cell.

"For years, a fundamental question in cell biology has gone largely unanswered — what proteins function in mitochondria?" said Vamsi Mootha, an associate member at the Broad Institute of Harvard and MIT and a Harvard Medical School assistant professor at Massachusetts General Hospital, who led the study. "By creating a comprehensive list, we now have a valuable resource that has already helped enhance our understanding of mitochondrial biology and disease."

Mitochondria are linchpins of cellular life, found within the cells of all eukaryotes from yeast to humans. These miniaturized organs ("organelles") are well known for their role in providing cellular energy. They have also been implicated in a wide range of normal and disease processes, including diabetes, neurodegeneration, cancer, drug toxicity and aging.

Although mitochondria have their own genome — a vestige from their days as free-living bacteria — the vast majority of the critical mitochondrial proteins are derived not from their genome, but rather from the nuclear genome. However, even with the wealth of genome sequence data now available, scientists have struggled to identify which genes encode the roughly 1,200 proteins that make up a functional mitochondrion.

Researchers from the Broad Institute, Harvard Medical School, and Massachusetts General Hospital worked together to address this problem, drawing on the power of a multi-faceted approach that includes large-scale, mass spectrometry-based proteomics to measure proteins in mitochondria from a variety of tissues; computational methods to help identify those proteins that cannot be reliably detected; and microscopy to confirm within human cells the localization of presumptive mitochondrial proteins.

"The technologies and analytical methods for measuring proteins on a large scale are really transforming what we can learn about human biology," said Steve Carr, director of the Proteomics Platform at the Broad Institute and a co-author of the Cell paper. "By applying them to mitochondria isolated from fourteen different mouse tissues, we've completed one of the most comprehensive proteomic analyses of any organelle to date."

As a result of their analyses, the researchers identified a total of 1,098 mitochondrial proteins to form a compendium they have named "MitoCarta," and which is available to the entire scientific community. Notably, about one-third of this inventory has not been previously linked to the organelle.

To shed light on the functions of the newly uncovered mitochondrial proteins, the researchers compared the proteins' corresponding gene sequences across hundreds of species, from humans and fish to fungi and bacteria. "Proteins with similar roles often share similar histories, meaning they're gained or lost together during evolution," said Mootha. "We decided to use this tendency to our advantage to decipher how some mitochondrial proteins work."

By examining the organelle's proteins through this evolutionary lens, the researchers uncovered a striking pattern. A group of key mitochondrial proteins, known to be absent in yeast but otherwise present among eukaryotes, are actually missing from several other single-celled species. In organisms that have them, including humans and other mammals, these proteins contribute to a boot-shaped, multi-protein structure, which forms the gateway to a critical step in the energy-generation process. By virtue of these proteins' shared — and unusual — past, Mootha and his colleagues were able to identify several additional proteins that are also associated with this crucial mitochondrial structure, known as complex 1.

In addition to offering insights into mitochondrial biology, these discoveries also paved the way for a breakthrough in understanding mitochondrial disease. For decades, doctors have diagnosed patients with deficiencies in complex I function. These disorders affect about 1 in 5,000 newborns, are genetic in origin, and are lethal in the first few years of life. Yet for many cases a culprit gene cannot be found. However, thanks to MitoCarta and its corresponding evolutionary analyses, the researchers and their collaborators at the University of Melbourne and Royal Children's Hospital in Australia identified a mutation in a novel gene, called C8orf38, as one cause of complex I disease.

"Our finding underscores the power of this protein catalogue to open new vistas on disease," said Mootha. "It promises to shed light not only on rare metabolic diseases, but common diseases as well."

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This work was supported by a grant from the National Institute of General Medical Sciences, one of the National Institutes of Health.

Written by Nicole Davis

Data access

The mitochondrial protein compendium (MitoCarta) is freely available to researchers on the web: www.broad.mit.edu/publications/MitoCarta. In addition, all of the raw mass spectrometry files are available for download at http://www.proteomecommons.org/data/show.jsp?id=7820.

Paper cited:

Pagliarini DJ et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell July 11, 2008.

About the Broad Institute of MIT and Harvard

The Broad Institute of MIT and Harvard was founded in 2003 to bring the power of genomics to biomedicine. It pursues this mission by empowering creative scientists to construct new and robust tools for genomic medicine, to make them accessible to the global scientific community, and to apply them to the understanding and treatment of disease.

The Institute is a research collaboration that involves faculty, professional staff and students from throughout the MIT and Harvard academic and medical communities. It is jointly governed by the two universities.

Organized around Scientific Programs and Scientific Platforms, the unique structure of the Broad Institute enables scientists to collaborate on transformative projects across many scientific and medical disciplines.

For further information about the Broad Institute, go to http://www.broad.mit.edu.

MIT reports finer lines for microchips : Advance could lead to next-generation computer chips, solar cells, more

MIT researchers have achieved a significant advance in nanoscale lithographic technology, used in the manufacture of computer chips and other electronic devices, to make finer patterns of lines over larger areas than have been possible with other methods.

Their new technique could pave the way for next-generation computer memory and integrated-circuit chips, as well as advanced solar cells and other devices.

The team has created lines about 25 nanometers (billionths of a meter) wide separated by 25 nm spaces. For comparison, the most advanced commercially available computer chips today have a minimum feature size of 65 nm. Intel recently announced that it will start manufacturing at the 32 nm minimum line-width scale in 2009, and the industry roadmap calls for 25 nm features in the 2013-2015 time frame.

The MIT technique could also be economically attractive because it works without the chemically amplified resists, immersion lithography techniques and expensive lithography tools that are widely considered essential to work at this scale with optical lithography. Periodic patterns at the nanoscale, while having many important scientific and commercial applications, are notoriously difficult to produce with low cost and high yield. The new method could make possible the commercialization of many new nanotechnology inventions that have languished in laboratories due to the lack of a viable manufacturing method.

The MIT team includes Mark Schattenburg and Ralf Heilmann of the MIT Kavli Institute of Astrophysics and Space Research and graduate students Chih-Hao Chang and Yong Zhao of the Department of Mechanical Engineering. Their results have been accepted for publication in the journal Optics Letters and were recently presented at the 52nd International Conference on Electron, Ion and Photon Beam Technology and Nanofabrication in Portland, Ore.

Schattenburg and colleagues used a technique known as interference lithography (IL) to generate the patterns, but they did so using a tool called the nanoruler--built by MIT graduate students--that is designed to perform a particularly high precision variant of IL called scanning-beam interference lithography, or SBIL. This recently developed technique uses 100 MHz sound waves, controlled by custom high-speed electronics, to diffract and frequency-shift the laser light, resulting in rapid patterning of large areas with unprecedented control over feature geometry.

While IL has been around for a long time, the SBIL technique has enabled, for the first time, the precise and repeatable pattern registration and overlay over large areas, thanks to a new high-precision phase detection algorithm developed by Zhao and a novel image reversal process developed by Chang.

According to Schattenburg, "What we're finding is that control of the lithographic imaging process is no longer the limiting step. Material issues such as line sidewall roughness are now a major barrier to still-finer length scales. However, there are several new technologies on the horizon that have the potential for alleviating these problems. These results demonstrate that there's still a lot of room left for scale shrinkage in optical lithography. We don't see any insurmountable roadblocks just yet."

The MIT team performed the research in the Space Nanotechnology Laboratory of the MIT Kavli Institute of Astrophysics and Space Research, with financial support from NASA and NSF.

Federation of American Societies for Experimental Biology : Get smart about what you eat and you might actually improve your intelligence

MIT researchers offer tantalizing evidence on how to make people smarter, naturally

New research findings published online in The FASEB Journal provide more evidence that if we get smart about what we eat, our intelligence can improve. According to MIT scientists, dietary nutrients found in a wide range of foods from infant formula to eggs increase brain synapses and improve cognitive abilities.

"I hope human brains will, like those of experimental animals, respond to this kind of treatment by making more brain synapses and thus restoring cognitive abilities," said Richard Wurtman, MD, senior researcher on the project.

In the study, gerbils were given various combinations of three compounds needed for healthy brain membranes: choline, found in eggs; uridine monophosphate (UMP) found in beets; and docosahexaenoic acid (DHA), found in fish oils. Other gerbils were given none of these to serve as a baseline. Then they were checked for cognitive changes four weeks later. The scientists found that the gerbils given choline with UMP and/or DHA showed cognitive improvements in tasks thought to be relevant to gerbils, such as navigating mazes. After these tests were concluded, the researchers dissected the mouse brains for a biological cause for the improvement. They found biochemical evidence that there was more than the usual amount of brain synapse activity, which was consistent with behaviors indicating higher intelligence.

"Now that we know how to make gerbils smarter," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal, "it's not too far a stretch to hope that people's intelligence can also be improved. Quite frankly, this can't happen soon enough, as every environmentalist, advocate of evolution and war opponent will attest."

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This article is scheduled for final publication in the November 2008 issue of The FASEB Journal (http://www.fasebj.org), which is published by the Federation of American Societies for Experimental Biology (FASEB) and is the most cited biology journal worldwide according to the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.

MIT Research : Media Lab celebrates co-founder Davenport's career

Symposium honors interactive media pioneer's legacy
David Chandler,
MIT News Office
June 25, 2008
Dozens of Media Lab faculty and alums gathered for a daylong symposium Friday, June 20, to celebrate the career of Glorianna Davenport, head of the lab's Media Fabrics group and a longtime innovator in film, video, interactive media and new ways of storytelling.
The event was in honor of Davenport's retirement after more than three decades at MIT, where she initially worked in the Film/Video Section before co-founding the Media Lab in 1985. In 2000, she was a co-founder of Media Lab Europe, based in Dublin. Over the years, dozens of her graduate students have gone on to found innovative companies, and many of them returned to describe their work at the symposium (or "media jam session," as the program described the event).
"I'm a media junkie," Davenport said at the event, held in the Media Lab's Bartos auditorium. "Not so much for the media that's out in the world," she explained, "but for using video to understand what I see."
That concept of using video as a tool for understanding has been a key element of Davenport's work through the years--both in her own creative endeavors, and in the methods she encourages her students to try. "There's no such thing as an unbiased story," she said. "When you play it back, it's never like it was."
That has often been a revelation to people, she said. "Students thought they could be neutral, but in fact the media maker is an improvisational collector."
Among the projects Davenport and her students have worked on were "Elastic Charles," in which a group of people each shot films depicting different aspects of the Charles River, and a three-year New Orleans project that resulted in a set of videodiscs (this was in the pre-DVD era) depicting how the city changed over time.
She has always emphasized the use of film or video cameras as a way of reaching a new understanding of one's environment, and has been especially interested in giving young children a chance to explore the media as a tool for learning.
One of her former students, Hans Peter Brondmo, who has created an online company called Plum.com that provides a way for people to collect and share pictures, video and audio files, documents, and web pages in an online archive, summed up the feelings that many of the event's speakers described in one way or another: "You would never say no," he said to Davenport, "though sometimes you would say something was kind of stupid. You would always inspire and encourage. You were a big inspiration to me."

MIT Research : Solar system's biggest impact scar discovered

MIT scientists solve riddle of Mars' two-faced nature

David Chandler,
MIT News Office
June 25, 2008
A new analysis of the topography and gravity of Mars by researchers at MIT and NASA has solved one of the biggest remaining mysteries in the solar system -- why the planet Mars has two completely different kinds of terrain, in its northern and southern hemispheres. In the process, they have identified what appears to be by far the largest impact scar found anywhere.
The giant basin that covers about 40 percent of the surface of Mars, sometimes called the Borealis Basin, is actually the remains of a colossal impact very early in the solar system's formation, the new analysis shows. The basin, 8,500 km across and 10,600 km long, is larger than the combined area of Asia, Europe and Australia, and about four times wider than the next-biggest impact basins known, the Hellas basin on Mars and the South Pole-Aitken basin on the moon.
The northern-hemisphere basin on Mars is one of the smoothest surfaces found anywhere in the solar system, and some geologists think it may once have contained an ocean in the early days of the planet. The southern hemisphere is high, rough, heavily-cratered terrain, which ranges from 4 to 8 km higher in elevation than the basin floor. Until now, nobody really knew why the two halves were so different.
The new findings are being reported this week in a paper in the journal Nature by MIT postdoctoral researcher Jeffrey Andrews-Hanna, Maria Zuber, MIT's E.A. Griswold Professor of Geophysics, and Bruce Banerdt of NASA-JPL. Accompanying this analysis of the elevations and gravitation of Mars, which shows clear signs of the impact basin, are two other papers that provide a theoretical analysis of the kind of impact that would have been required to create it.
The mystery of how to explain the two-faced nature of the Martian surface has been perplexing planetary scientists ever since the first comprehensive images of the surface were beamed back to Earth from spacecraft in the late 1970s. For many years, there have been two main alternatives: Either some internal process related to the planet's molten subsurface layers, or an ancient impact.
But the impact idea, originally proposed in 1984 by Steven Squyres of Cornell University, now the lead scientist on the Mars Exploration Rovers project, and Don Wilhelms of the U.S. Geological Survey, had quickly fallen into disfavor because the shape of the basin didn't seem to match the expected round shape for a crater, Andrews-Hanna says. "There wasn't any observational evidence" to support the idea, he says.
Since then, other giant impact basins, including the South Pole-Aitken basin on the moon, have been discovered that are elliptical, rather than circular. But it took a complex analysis of the Martian surface, based on both elevation data and data on its gravitational field gathered by many years of spacecraft observations, to reveal the clear elliptical shape of the Borealis Basin on Mars.
One complicating factor was that since the time of the impact -- which must have been at least 3.9 billion years ago -- giant volcanos have formed along one part of the basin rim, and created a huge region of high, rough terrain that obscures the outlines of the basin. It took a combination of the gravity data from the Mars Reconnaissance Orbiter-- which tends to reveal underlying structure -- with the data on current surface elevations from Mars Global Surveyor, to reconstruct a map of Mars elevations as they existed before the volcanos erupted.
With that reconstruction, a very clear elliptical basin shape emerged, Andrews-Hanna says. The match between a perfect ellipse and the traced boundary line between the two topographic regions was startling. And in addition to the elliptical boundary of the basin, there are also signs along part of the rim of a possible second, outer ring -- a typical characteristic of large impact basins. "An impact is really the only mechanism that can produce these large-scale elliptical depressions, these large holes in the ground," Andrews-Hanna says.
"We haven't proved the giant-impact hypothesis," Andrews-Hanna says, "but I think we've shifted the tide. The majority of the evidence is now in favor of the giant impact."When he first presented some of these results at planetary science meetings, "since the idea has been unpopular for so long, I expected people to jump on me," he says. "But people have been very receptive."
In fact, both Andrews-Hanna and Zuber, until they carried out this analysis, had been believers in the alternative theory. "I can't believe I'm involved in this," says Zuber, who is head of MIT's department of Earth, Atmospheric and Planetary Sciences. "I've been a supporter of the internal models for years." But when the evidence from the surface reconstruction became clear, she says, they had to go where the data led. "We thought, people aren't going to buy this, but you've got to say what you've got to say."
And in fact, she says, the peer-reviewers of the paper "were very positive, very constructive, they commented about how careful we were."
And identifying this huge scar of an ancient impact, she says, "is pretty exciting." Until now, nobody had clearly identified signs of any ancient impact in that size range. There are one or two even larger impacts thought to have occurred in the early solar system, a controversial theory that there was one on the innermost planet Mercury, and a widely accepted one that the Earth was struck by a planet as big as Mars, melting the crust and ejecting it into space where some of it clumped together to form our moon.
But in both of those cases, the impacts were so enormous that they completely obliterated all visible signs of the event. It is only through indirect analysis, including study of rocks brought back from the moon by the Apollo astronauts, that these giant ancient impacts have been reconstructed. In terms of impacts that left visible basins, the largest known were the Hellas basin on Mars (about 2,400 by 1,800 km) and the moon's South Pole-Aitken basin (about 2,100 by 1,500 km).
"We knew there must be impacts between these size ranges," Zuber says. "But nobody had identified one." Analysis in the theoretical papers accompanying this one show that the impacting object that produced the huge basin on Mars must have been about 2,000 km across - larger than Pluto -- and struck at an angle of about 45 degrees, creating the oval shape of the basin.
The new finding adds yet another major event to the growing list of large impacts that have been recognized over the last few decades as having shaped the planets and moons of the solar system as we know them today. "The early solar system was a very dangerous place to be a planet," Andrews-Hanna says. "But without those impacts, we wouldn't have the planets as we know them today."
The work was supported by a grant from the Mars Reconnaissance Orbiter project at NASA.

MIT Research : New probe may help untangle cells' signaling pathways

Anne Trafton, News OfficeJune 27, 2008
MIT researchers have designed a new type of probe that can image thousands of interactions between proteins inside a living cell, giving them a tool to untangle the web of signaling pathways that control most of a cell's activities.
"We can use this to identify new protein partners or to characterize existing interactions. We can identify what signaling pathway the proteins are involved in and during which phase of the cell cycle the interaction occurs," said Alice Ting, the Pfizer-Laubach Career Development Assistant Professor of Chemistry and senior author of a paper describing the probe published online June 27 by the Journal of the American Chemical Society.
The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.
To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.
Their work is conceptually related to an approach that uses GFPs (green fluorescent proteins), which glow when activated, as probes. Half of each GFP molecule is attached to the proteins of interest, and when the proteins interact, the GFP halves fuse and glow. However, this technique results in many false positives, because the GFP halves seek each other out and bind even when the proteins they are attached to are not interacting, said Ting.
The new probes could be used to study nearly any protein-protein interaction, Ting said. The researchers tested their probes on two signaling proteins involved in suppression of the immune system, and on two proteins that play a role in cell division. They are currently using the probe to image the interaction of proteins involved in synapse growth in live neurons.
Lead author of the paper is Marta Fernandez-Suarez, a graduate student in chemistry. Biology graduate student T. Scott Chen is also an author of the paper.
The research was funded by the National Institutes of Health and the McKnight, Dreyfus and Sloan Foundations.

MIT Research : MIT-led team finds language without numbers

Amazonian tribe has no word to express 'one,' other numbers
Anne Trafton, News OfficeJune 24, 2008
An Amazonian language with only 300 speakers has no word to express the concept of "one" or any other specific number, according to a new study from an MIT-led team.
The team, led by MIT professor of brain and cognitive sciences Edward Gibson, found that members of the Piraha tribe in remote northwestern Brazil use language to express relative quantities such as "some" and "more," but not precise numbers.
It is often assumed that counting is an innate part of human cognition, said Gibson, "but here is a group that does not count. They could learn, but it's not useful in their culture, so they've never picked it up."
The study, which appeared in the June 10 online edition of the journal Cognition, offers evidence that number words are a concept invented by human cultures as they are needed, and not an inherent part of language, Gibson said.
The work builds on a study published in 2004, which found that the Piraha had words to express the quantities "one," "two," and "many." The MIT researchers observed the same phenomenon when they asked Piraha speakers to describe sets of objects as they were added, from one to 10.
However, the MIT team decided to add a new twist--they started with 10 objects and asked the tribe members to count down. In that experiment, the tribe members used the word previously thought to mean "two" when as many as five or six objects were present, and they used the word for "one" for any quantity between one and four.
This indicates that "these aren't counting numbers at all," said Gibson. "They're signifying relative quantities."
He said this type of counting strategy has never been observed before, although it may also be found in other languages believed to have "one," "two," and "many" counting words.
The paper is part of a larger project that investigates the relationship between Piraha culture and their cognition and language, testing some claims by Daniel Everett, a linguist at Illinois State University, in a 2005 issue of Current Anthropology.
One other discovery of the project is that the Piraha can perform exact matching tasks as long as there is no memory component to them, but once there is a memory component, they approximate their matches. This suggests that language is a cognitive technology that aids humans in memory tasks.
Lead author of the paper is Michael Frank, a graduate student in Gibson's lab. Other authors are Evelina Fedorenko, a postdoctoral associate at the McGovern Institute for Brain Research at MIT, and Everett.

Massachusetts Institute of Technology : New probe may help untangle cells' signaling pathways

Anne Trafton, News Office
June 27, 2008

MIT researchers have designed a new type of probe that can image thousands of interactions between proteins inside a living cell, giving them a tool to untangle the web of signaling pathways that control most of a cell's activities.

"We can use this to identify new protein partners or to characterize existing interactions. We can identify what signaling pathway the proteins are involved in and during which phase of the cell cycle the interaction occurs," said Alice Ting, the Pfizer-Laubach Career Development Assistant Professor of Chemistry and senior author of a paper describing the probe published online June 27 by the Journal of the American Chemical Society.

The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.

To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.

Their work is conceptually related to an approach that uses GFPs (green fluorescent proteins), which glow when activated, as probes. Half of each GFP molecule is attached to the proteins of interest, and when the proteins interact, the GFP halves fuse and glow. However, this technique results in many false positives, because the GFP halves seek each other out and bind even when the proteins they are attached to are not interacting, said Ting.

The new probes could be used to study nearly any protein-protein interaction, Ting said. The researchers tested their probes on two signaling proteins involved in suppression of the immune system, and on two proteins that play a role in cell division. They are currently using the probe to image the interaction of proteins involved in synapse growth in live neurons.

Lead author of the paper is Marta Fernandez-Suarez, a graduate student in chemistry. Biology graduate student T. Scott Chen is also an author of the paper.

The research was funded by the National Institutes of Health and the McKnight, Dreyfus and Sloan Foundations.