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Monday, February 24th, 2014

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    5:00a
    Looking for first light
    From a cosmic perspective, one could argue that we all come from stars.

    Nearly 14 billion years ago, the Big Bang spawned the universe, yielding a primordial mixture of dark matter and gas within the first few minutes. The lightest elements in this gas — hydrogen and helium — were fused in the Big Bang itself, but the other elements that have since evolved into solar systems, planets, and living organisms were formed much later.

    Scientists have traced production of these heavier elements, such as carbon and oxygen, to nuclear fusion within stars. But what exactly created the first stars, and when did that happen?

    This question of stellar origin is the focus of Robert Simcoe, an associate professor of physics at MIT. Using telescopes on Earth and in space, Simcoe is peering far into the universe’s past, searching for a period when the first stars blinked on.

    “What my field is progressing toward is [an understanding of] when and how the first stars turned on, and when galaxies started to look like they do today,” says Simcoe, who recently earned tenure. “We’re starting to see distant objects [with] very low chemical content. That’s one hint that you’re getting to an interesting time.”

    Simcoe’s work indicates that something interesting may have taken place a mere 750 million years after the Big Bang, when the universe was only 5 percent of its present age. Last year, he was part of a team that observed the most distant known quasar — a galaxy that shines especially brightly because of an accreting black hole at its center; the light from this object has been traveling to Earth since then. Yet in the quasar’s immediate surroundings, the team found a large structure of diffuse hydrogen gas with no evidence of heavy metals. The finding suggested that this early quasar belonged to a period in which stars had yet to appear and pollute their surroundings. Simcoe says more distant quasars will have to be discovered and characterized before scientists can confirm exactly when the first stars arose — but the recent detection of pristine gas is a promising start.

    “Right now it’s a pretty fuzzy boundary of what we’re looking for,” Simcoe says. “But you might as well think expansively.”

    Expanding an astronomer’s view

    Simcoe began thinking expansively as a child. He grew up in Westborough, Mass., a suburb west of Boston, where the night sky offered clear views of distant stars. A third-grade project on space sparked Simcoe’s interest in observation, and he saved up for a small telescope, which he used in his backyard to pick out constellations. But the telescope’s magnification was too weak to detect far-off galaxies.

    One weekend, Simcoe’s father took him on a road trip to Vermont, where amateur telescope-makers had gathered to swap parts and discuss building techniques. The Simcoes came away with a piece of glass that they honed over a period of weeks in the family basement, grinding with progressively finer abrasives to shape the curvature of an optical telescope objective. They fitted the mirror into a cardboard tube, and pointed it at the sky. The payoff was worth the work: Suddenly, Simcoe had a view of multiple galaxies, including Andromeda, and gaseous nebulae around the Milky Way.

    An avid musician in high school, Simcoe also contemplated a future as a pianist. But when an audition at the Tanglewood summer music festival in western Massachusetts fell through, he reconsidered. An advertisement in the back of an astronomy magazine convinced him to try astronomy camp, and he soon headed to Arizona, where he learned to observe the sky with even stronger telescopes.

    The experience propelled him to Princeton University, where, as an undergraduate, he played a minor part in a major project: the Sloan Digital Sky Survey, the largest, most detailed map of the universe to date, depicting hundreds of thousands of galaxies and quasars.

    “This was one of the biggest experiments to happen in astronomy in the last 20 years,” Simcoe recalls. “It was the first time people made a digital map of a good chunk of the sky, and that seemed exciting and ambitious to me.”

    The beginnings of a star search

    From Princeton, Simcoe headed west, to the California Institute of Technology, where, as a graduate student, he started digging into the mystery of the first stars. At the time, scientific theory held that heavy elements like oxygen and carbon would only be found near the stars and galaxies that produced them. But astronomers began to observe evidence of chemicals far from any galaxy — a puzzle that theories failed to explain.

    In his thesis, Simcoe analyzed the distribution of chemicals throughout the universe, and came up with an estimate of the volume of chemicals that may have leaked out of galaxies. His work ultimately informed more realistic models for how galaxies evolve.

    “We used to think of galaxies as little vacuum cleaners: They would suck in gas and turn it into stars,” Simcoe explains. “Instead, it’s almost like they’re a factory, taking in pure pristine gas from the Big Bang, polluting it with these other chemicals and spewing it back out.”

    Looking for ‘generation zero’

    In 2000, a group of universities commissioned the twin Magellan Telescopes in Chile, affording a view of extremely distant objects, like the old quasars and galaxies that help in identifying the era of the first stars. MIT is a shareholder in the telescopes, meaning the Institute’s researchers have regular access to the facility — an opportunity Simcoe seized.

    He joined MIT’s physics department as a Pappalardo Postdoctoral Fellow in 2003, and soon after, accepted a faculty position. Since then, he has taken a handful of trips each year to Chile, spending a week at a time at the telescopes, in the remote Atacama Desert.

    The observatory includes a dormitory, where scientists sleep during the day. Before nightfall, they rise to calibrate the telescopes before heading to the dining hall.

    “Around the dinner table you can get all the scuttlebutt from different places,” Simcoe says. “It’s outside the conference circuit, where everyone’s more formal. Here, everyone’s tired, off their guard — it’s very much like camp.”

    When the sun goes down, the work begins, as astronomers spend the night analyzing readouts of objects captured by the telescopes. Based on such observations, Simcoe has identified a number of far-off objects, including the quasar whose spectrum lacked heavy elements.

    In the next few years, Simcoe will continue looking for signs of the universe’s first stars, using Magellan, other observatories on Earth, and the Hubble Space Telescope. Today’s stars are produced with “a little carbon and oxygen sprinkled in with gas,” he says. But immediately following the Big Bang, only hydrogen and helium were in any supply. Simcoe says the very first stars may have formed from molecular hydrogen cooling — a very different process than the atomic cooling from carbon and oxygen that gives rise to today’s stars. Detecting far-off stars composed of hydrogen alone, he says, remains a distant goal for astronomers.

    “Once you’ve reached those, you know you’re at generation zero,” Simcoe says. “We don’t know exactly when that happened, or how we’re going to get there. But we think we’re in the right ballpark as far as how far back we need to look.”
    8:00p
    A paper diagnostic for cancer
    Cancer rates in developing nations have climbed sharply in recent years, and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes, but screening approaches such as mammograms and colonoscopy, used in the developed world, are too costly to be implemented in settings with little medical infrastructure.  

    To address this gap, MIT engineers have developed a simple, cheap, paper test that could improve diagnosis rates and help people get treated earlier. The diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person has cancer. This approach has helped detect infectious diseases, and the new technology allows noncommunicable diseases to be detected using the same strategy.

    The technology, developed by MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, relies on nanoparticles that interact with tumor proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient’s urine.

    “When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis,” says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. “For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.”

    Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, is the senior author of a paper describing the particles in the Proceedings of the National Academy of Sciences the week of Feb. 24. The paper’s lead authors are graduate student Andrew Warren, postdoc Gabriel Kwong, and former postdoc David Wood.

    Amplifying cancer signals

    In 2012, Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumor proteins that would be hard to detect on their own. These proteins, known as matrix metalloproteinases (MMPs), help cancer cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.

    The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumor sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.

    In the original version of the technology, these peptides were detected using an instrument called a mass spectrometer, which analyzes the molecular makeup of a sample. However, these instruments are not readily available in the developing world, so the researchers adapted the particles so they could be analyzed on paper, using an approach known as a lateral flow assay — the same technology used in pregnancy tests.

    To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.

    “This is a clever and inspired technology to develop new exogenous compounds that can detect clinical conditions with aberrantly high protease concentrations,” says Samuel Sia, an associate professor of biological engineering at Columbia University who was not involved in the research. “Extending this technology to detection by strip tests is a big leap forward in bringing its use to outpatient clinics and decentralized health settings.”

    In tests in mice, the researchers were able to accurately identify colon tumors, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients.

    “This is a new idea — to create an excreted biomarker instead of relying on what the body gives you,” she says. “To prove this approach is really going to be a useful diagnostic, the next step is to test it in patient populations.”

    Developing diagnostics

    To help make that happen, the research team recently won a grant from MIT’s Deshpande Center for Technological Innovation to develop a business plan for a startup that could work on commercializing the technology and performing clinical trials.

    Bhatia says the technology would likely first be applied to high-risk populations, such as people who have had cancer previously, or had a family member with the disease. Eventually, she would like to see it used for early detection throughout developing nations.

    Such technology might also prove useful in the United States, and other countries where more advanced diagnostics are available, as a simple and inexpensive alternative to imaging. “I think it would be great to bring it back to this setting, where point-of-care, image-free cancer detection, whether it’s in your home or in a pharmacy clinic, could really be transformative,” Bhatia says.

    With the current version of the technology, patients would first receive an injection of the nanoparticles, then urinate onto the paper test strip. To make the process more convenient, the researchers are now working on a nanoparticle formulation that could be implanted under the skin for longer-term monitoring.

    The team is also working to identify signatures of MMPs that could be exploited as biomarkers for other types of cancer, as well as for tumors that have metastasized.

    The research was funded by a National Science Foundation Graduate Research Fellowship, a Mazumdar-Shaw International Oncology Fellowship, the Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Burroughs Wellcome Fund, the National Cancer Institute, and the Howard Hughes Medical Institute.

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