Brain surgery remains one of the more complex procedures in the clinical arsenal, an intervention any doctor would like to avoid if possible. But many conditions - a growing brain tumor, a bleeding hemorrhage - require the surgeon to go in, opening the skull, dodging blood vessels, and preserving healthy tissue to correct the problem. If these maladies were somehow preventable or treatable with a medication, it could cut down on the complications and cost of neurosurgery. Even so, you might be surprised to find a surgeon doing the research that could someday reduce his own workload.

That’s the case with Issam Awad, professor of surgery at the University of Chicago Medical Center, and the latest paper in his project studying an abnormality of the brain’s blood vessels. Cerebral cavernous malformation (CCM), alternatively known as cavernous angioma, occurs when the small blood vessels of the brain grow abnormally large. These malformations can occasionally form a dangerous lesion, leading to headaches, bleeding in the brain, or stroke. But it wasn’t until the routine use of MRI technology until clinicians discovered just how commonly CCM can be found - 1 in 500 people - even though it is often non-symptomatic.

The presence of non-symptomatic CCM complicates the matter further for neurosurgeons, who must decide whether to perform surgery to correct the lesion or wait to see if it worsens. This dilemma is especially difficult in patients with a family history of CCM, which makes up about one-third of the cases. Waiting to see if the angioma is going to become problematic enough to require surgery can be a frustrating experience.

“There is currently no treatment in clinical use to either prevent the formation or the maturation of these lesions,” Awad said. “The way we deal with them now is we wait until a lesion gets bad or does something bad, and then we take it out.”

Awad and colleagues Douglas Marchuk from Duke University and Mark Ginsberg at the University of California, San Diego have used those familial CCM cases to find the cause of the condition, focusing on a gene called KRIT1 (or CCM1 for its clinical significance). By knocking down KRIT1, they could create a mouse model that formed CCM lesions, and study the cellular signals that accompany the condition. It turned out that reducing the activity of KRIT1 increased the activity of a signal called ROCK, which made CCM lesions leakier and more severe. CCM lesions removed surgically from human subjects by Awad also tested for high levels of ROCK, suggesting that the mechanism was the same across species.

So the obvious hypothesis to test was whether an inhibitor of ROCK could block the formation of CCM lesions. For a paper published yesterday in Stroke, researchers from the three laboratories performed the experiments in their mouse model of CCM, treating the mice for four months with a ROCK inhibitor drug called fasudil. When they compared the brains of these drug-treated animals to the brains of animals treated with a placebo, they found fewer lesions, smaller lesions, and a reduction in inflammation and hemorrhage after fasudil.

“This animal model and humans have lesions that are aggressive and symptomatic: They leak blood, they show inflammatory properties, and endothelial cells multiply or proliferate,” Awad said. “None of these features were present in the fasudil-treated mice. It was like the lesion was chilled down and shrunk.”

Though promising, this early experiment was performed in only a small number of mice. More extensive testing in animals - and if everything goes well, in human clinical trials - will be required before the drug can be deployed in the neurology practice. Fasudil is also not yet approved for use in the United States, though it is used in Japan for a different neurological condition and has been “clinically well tolerated” there, Awad said.

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Finding the cause and the cure for a deadly disease is a little bit like investigating a murder. Clinicians collect clues from their patients, bring them back to the lab, and try to reconstruct the crime and identify the killer. For amyotrophic lateral sclerosis (aka ALS or Lou Gehrig’s Disease), this investigation has lasted over a hundred years - since neurologist Jean-Marie Charcot first described the disease in 1874. But it’s only in the last two decades that ALS researchers have started to find major breaks in the case, revealing genetic clues to the origin of this deadly neurodegenerative disease. At a special ALS gathering at the University of Chicago, Medical Center neurologist Raymond Roos told nearly 200 patients and caregivers that the case may finally be cracked soon.

“I think the field is on fire now,” said Roos, the Marjorie and Robert E. Straus Professor of Neurology. “I think it’s astounding and exciting what’s going on with respect to neurodegenerative diseases and absolutely ALS. We have all these things piling up now and we are continuing [to look]. Should we be optimistic about the future? Yes.”

Wednesday’s gathering, put together by the Greater Chicago Chapter of the ALS Assocation, was a unique two-part event featuring both a symposium for researchers of the disease and a luncheon/health expo for the patients and their families. In one room of historic Ida Noyes Hall, 14 Chicago scientists studying the origins of ALS and developing new treatments for what is currently an incurable disease shared their latest results. Meanwhile, patients and their families learned about medical devices and advocacy opportunities, and shared stories of how they cope with their disorder.

The day’s scientific component demonstrated both why the ALS investigation has taken so long, and why Roos thinks there is cause for optimism. The central mystery of ALS is why it selectively targets the motor neurons of the nervous system, the extremely long cells that deliver instructions from the brain to the muscles of the body. As the motor neurons die off, the patient experiences a progressive paralysis, losing the ability to maintain balance, walk, and eventually, breathe. Figuring out what causes this specific population of neurons to perish will point the way to treatments that slow or even reverse the progression of the disease.

For suspects, scientists have looked to genes. Roughly 10 percent of ALS cases are inherited through generations of families, indicating a genetic cause. While this population might be only a small minority of cases compared to the more common “sporadic” cases, they could be a foothold along the path to understanding both types of ALS.

“Those are very important even though they make up this small group, because they open a window,” Roos said. “If we can identify the gene that’s mutated, we can figure out what the function of that gene is. The hope and assumption and, I think, the reality, is that information will guide us into understanding the non-inherited, sporadic form.”

In 1993, scientists discovered the first ALS-associated gene/suspect, called SOD1. Though mutations of this gene explain only 20 percent of the familial 10 percent, they have been an important clue into exactly what goes wrong inside a motor neuron during the disease’s tragic march. The morning’s sessions zoomed in on these details, describing how a faulty SOD1 can kill off a cell through to the aggregation of cellular proteins, the interruption of the cell’s highway-like transport system (presented by UIC’s Gerardo Morfini and Scott Brady), and the creation of a “toxic channel” (as told by UCMC’s Michael Allen). The damage caused by SOD1 mutants might not even be limited to the motor neurons themselves, as Roos presented research demonstrating its toxic activity in the cells surrounding those neuronal types.

The path from what goes wrong to the creation of new potential therapies for ALS was explained by Richard Silverman, a chemist from Northwestern University. By screening for compounds that prevent the type of protein aggregations observed in the motor neurons of ALS patients, chemists hope to design new drugs that will slow the damage and hopefully, the physical symptoms they produce. Silverman detailed the incremental design of two new compounds in his laboratory that, in animal studies, produce an extension of life that is two to three times longer than seen with the only drug currently approved for use in ALS, riluzole.

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By John Easton

Location, location, location. The three most important words in real estate turn out to be significant for health as well.

In today’s issue of the New England Journal of Medicine, a research team based at the University of Chicago show that low-income women with children who moved from high-poverty to lower-poverty neighborhoods experienced notable long-term reductions in diabetes and extreme obesity.

The research was the first to employ a randomized experimental design on a large scale to learn about the connections between neighborhood poverty and health.

For the study, Jens Ludwig and Stacy Lindau from the University of Chicago, and a team of scholars from around the country, studied 4,498 poor women and children, who from 1994 to 1998, enrolled in a residential mobility program called Moving to Opportunity.

The U.S. Department of Housing and Urban Development (HUD) operated MTO in five United States cities - Baltimore, Boston, Chicago, Los Angeles and New York.

MTO was based on the Chicago Gautreaux program, established in the late 1970s as part of a court-imposed public housing desegregation remedy. It was designed to study the effect of neighborhoods on employment, income and education in families with children living in cities with a 40% or greater poverty rate. It wasn’t originally focused on health, but Ludwig and his team were curious about how poverty in the U.S. correlated with health issues such as obesity and diabetes and they persuaded HUD to add the public health research component.

Moving to Opportunity enrolled low-income families with children living in distressed public housing. Families volunteered for the experiment, and based on the results of a random lottery, were offered the chance to use a housing voucher subsidy to move into a lower-poverty community. Other families were randomly assigned to a control group that received no special assistance under the program.

According to HUD: The four Chicago census tracts targeted for MTO had an average poverty rate of 67 percent and contained six public and assisted housing developments, which housed a total of 2,197 households. The average income among residents of the six targeted projects was $7,114, and over 75 percent of residents received some form of public assistance. Virtually all of these households were African American (99.4) and 70 percent were female-headed.

The NEJM study collected information during 2008-10 on families who had enrolled in the program 10 to 15 years before. The research team directly measured the heights and weights of MTO participants, and it also collected blood samples to test for diabetes.

At the time of follow-up, 17 percent of the women in the study’s control group were morbidly obese (body mass index at or above 40), and 20 percent had diabetes. However, in the group of women who were offered housing vouchers to move to lower-poverty neighborhoods, the rates of morbid obesity and diabetes were both about one fifth lower than in the control group.

“The initial aim of the study was to help families be safer, but it turns out there’s an effect on these really important health outcomes that’s in the ballpark of lifestyle and medical interventions,” Ludwig said. “That’s pretty striking,”

“This is one of the first studies to show that where you live - the circumstances of your neighborhood, the social characteristics of the people around you - all these things may play a role in your own health,” said Harlan Krumholz, a cardiologist at the Yale School of Medicine who was not involved in the study, during an interview with the Los Angeles Times. “Your health is not just what happens to you, but is influenced by all of those around you and the environment. … Some environments are toxic to health.”

“Giving a low-income woman the opportunity to move with her children to a less impoverished neighborhood appears to lower her risk of … two of the biggest health problems facing our country,” said Lindau, associate professor in obstetrics and gynecology, and an expert in urban health.

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What made the human brain? According to Stanley Kubrick and Arthur C. Clarke, it was a giant obsidian monolith inspiring primates to use tools and weapons. Scientists have taken a more nuanced approach, looking for the biology behind the complex structures and enhanced function of the human brain. But merely comparing the genes expressed in adult human brains to those of other animals yielded few promising differences, leading scientists to focus on changes in the regulation of old genes rather than the arrival of new genes. After all, the construction of a structure as important as the brain cannot rely on unpredictable, novel genes with new functions, right?

However, those young genes are recently taking on a higher profile. In a 2010 paper, the University of Chicago laboratory of Manyuan Long demonstrated that new genes exclusive to a given species can be just as critical to an organism’s survival as the old, conserved genes it shares with other species. The implication at the time was that what makes us uniquely human could lie in those “young” genes that only appeared in our genome relatively recently.

“Animal models have proven to be very useful and important for dissecting human disease,” said Sidi Chen in 2010 about that study. “But if our intuition is correct, some important health information for humans will reside in the unique parts of the human genome.”

A new study from Long’s lab appearing yesterday in PLoS Biology identifies one important place where those new genes may play role: the human brain. By merging a database of gene age with gene transcription data from humans and mice, researchers looked for where young genes specific to each species were expressed.They found that a higher percentage of primate-specific young genes were expressed in the brain compared to mouse-specific young genes. Human-specific young genes also were more likely to be expressed in uniquely human brain structures, such as the neocortex and prefrontal cortex.

“Newer genes are found in newer parts of the human brain,” said Yong Zhang, PhD, postdoctoral researcher and first author on the study. “We know the brain is the most remarkable difference between humans and other mammals and primates. These new genes are a candidate for future studies, as they are more likely to underlie this difference.”

Another intriguing finding in the gene age data was inspired by Zhang’s visit to the obstetrician with his pregnant wife. While viewing an ultrasound of his unborn child, Zhang said he realized that much of human development takes place during fetal stages - suggesting those early months should be a critical time for gene expression. As predicted, young human-specific genes in the brain were more likely to be turned on during fetal or infant development.The early activity of these genes suggests scientists should be looking at earlier developmental stages for genetic activity that ultimately shapes the complexity of the human brain.

“What’s really surprising is that the evolutionary newest genes on the block act early,” said co-author Patrick Landback, a graduate student in Long’s laboratory. “The primate-specific genes act before birth, even when a human embryo doesn’t look very different from a mouse embryo. But the actual differences are laid out early.”

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Many of the most interesting processes in nature are so fast, they can make “a blink of an eye” look like a millennium. Cellular proteins undergo elaborate transformations in as little as a picosecond - one millionth of one millionth of a second. That astonishing time scale presents an enormous challenge to scientists who would like to study the structure and behavior of those proteins. To catch the extremely fleeting moments of transition between different structural states of one such protein, a University of Chicago laboratory used a strategy straight out of science fiction: freezing time.

Xiaojing Yang, a senior research professional in the laboratory of Keith Moffat, wanted to look at a particular protein called a bacteriophytochrome, a red light photoreceptor from bacteria related to phytochromes in plants. Photoreceptors are found everywhere in nature, from plants to eyes, and are activated by light to change their shape and transform a light signal into a biological signal.  Yang was interested in the contortions a photoreceptor makes when changing from the “dark” state to the “light” state, and chose a particular phytochrome from the bacterial species Pseudomonas aeruginosa.

Yang started with a method called X-ray crystallography, where proteins are maneuvered into crystal formation and then imaged at the atomic level using an X-ray beam. With traditional X-ray crystallography, Yang could determine the structure of the P. aeruginosa phytochrome in the dark state, before activation with the light signal - data she reported in a 2008 PNAS paper. But in order to see the transition between dark and light in finer detail, the researchers needed to develop a new trick.

“We applied an innovative application of crystallography called temperature-scanning cryocrystallography, where we use temperature to mimic time,” Yang said of the work, published this week in Nature. “So this is a new way of doing dynamic crystallography.”

Cryocrystallography, or “cryotrapping,” involves performing the method at a very low temperature to freeze the target molecule in a particular conformation. The temperature-scan aspect that Yang and colleagues added was to hold the crystal at an escalating series of temperatures (from -279° F to -135° F), each one moving the super-fast structural changes the slightest bit forward. The researchers could then do an X-ray scan at each temperature level to capture those normally-fleeting in-between stages.

“We shine the light at different temperatures, higher and higher,” Yang said. “The reaction progresses further as the temperature rises, and then you have a different mixture of reaction intermediates.”

“It’s a cunning way of slowing things down from picoseconds to minutes or even tens of minutes,” said Moffat, Louis Block Professor of Biochemistry & Molecular Biology at UChicago.

The experiments, using ten temperature levels in all, revealed three predominant intermediate states, called L1, L2, and L3. Transitions between states resemble a “molecular earthquake,” Moffat said, with the changes initially appearing at one corner of the light-sensitive chromophore of the phytochrome before spreading outwards until the entire structure is in flux. And as dramatic as the motion is, it’s only the initial steps of the phytochrome’s dance. Moffat uses the analogy of filming a sprint to describe the action they captured - the flash of light that starts the reaction is the starting gun - and says that they are so far only able to observe the first 15 meters of a 100 meter dash.

“We’re not in a position to observe the rest of the race,” Moffat said. “Yes, we would like to see the entire race going all the way to the finish, but we believe that the overall reaction from beginning to end involves quite a large molecular convulsion, which is probably not compatible with the crystals.”

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Almost everyone has experienced the boredom of sitting through someone’s vacation photos, forcing a wan smile as a friend hands you picture after picture of beaches, museums, and old buildings. But if you’ve been to the same destination as your friend, there’s an allure to seeing how their experience of a particular place compares to your own. Discussing a gelato stand you both visited outside the Uffizi gallery in Florence or debating the merits of ocean-side vs. sound-side in the Outer Banks can bring a friendship closer. But can that communal photo-sharing power be captured and channeled into improving people’s health?

That concept is a novel component of assistant professor of medicine Arshiya Baig’s pilot project to improve diabetes outcomes in the Chicago Latino community, Picture Good Health/Imagínate una Buena Salud. Designed in cooperation with churches in the predominantly Mexican neighborhood of Little Village, Baig’s program offers focus group classes with Latinos diagnosed with diabetes, seeking to improve their diet, exercise, and disease control. At each of the eight weekly sessions, participants go through education, counseling, and activities to help manage their diabetes. But each meeting begins with a novel concept, called “photovoice,” that puts the storytelling potential of photography to use as a stimulant of healthy discussion.

“We thought we would do something fun, so we are giving disposable cameras to everyone in the intervention group, and they get to take photos of their life with diabetes,” Baig said. “Then each class starts off with a conversation around those photos. People can share stories, they can problem solve, and our class leader is trained to facilitate a conversation. It’s probably the most innovative part of the study.”

The concept of photovoice was not created by Baig, but it is typically used by researchers for different purposes. Typically, the idea of giving subjects cameras and asking them to document their situation is used as a “needs assessment” to help design an intervention. For example, one project asked teenagers in an urban area to photograph negative elements in their daily life and community. Researchers or policy makers could then look at those photos to find places where an intervention could make the largest impact, such as cleaning up abandoned buildings or providing more supervision during walks to school.

However, in Picture Good Health, the photovoice method is the intervention. Participants are told only to document things in their life that are relevant to living with diabetes. After the photos are developed, they can choose which ones to share with the group during the first half-hour of each week’s session. The photographer explains what the photo means to him or her, and then the group discusses from there.

Second-year Pritzker medical student Matthew Stutz joined Baig’s project this summer to start analyzing the photovoice component of the focus groups. He found that the participant’s photos covered a wide range of topics, from the obvious (food, diabetes medications) to more general influences such as their home, workplace, neighborhood, and family. A photo of loaves of white and wheat bread might kick off a group discussion of health grocery choices, or a picture of an ashtray could trigger participants to talk about the methods they have used to try and quit smoking. One man shared a picture of a park and said it reminded him of his deceased daughter, inspiring the other participants to talk about family members they had lost - a topic that wouldn’t typically be on the agenda for a diabetes intervention.

“I think of photovoice as an easy mechanism for someone to convey emotions, experiences, losses, gains, without having to verbalize it,” Stutz said. “By having a prop or a mechanism to share, I feel we can gain a lot more ground and depth and conversation.”

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By Meghan Sullivan

What is it about viruses that so easily captures our attention? With the teeth mostly taken out of bacterial infections by the advent of penicillin and parasites a rare and mostly exotic concern, viruses remain one nemesis that we often struggle to treat. Unlike complex bacteria and parasites, viruses are little more than genetic material wrapped up in a vessel designed to take its blue prints to the next host. Once in a host, viruses inject their genetic material into cells and take over the cellular machinery to carry out their lifecycles. Imagine terrorists sneaking into a Ford factory and using the assembly lines to crank out WMDs. Infected cells eventually die, but not before triggering immune responses (coughing, sneezing, etc) that aide their spread to the next host.

Taken starkly, viruses execute an elegant life cycle. If the aim of life is to pass on one’s genetic material, viruses have succeeded by reducing themselves to only genetic material, relying on other organisms for the messy business of replicating and spreading. The only way to make the process more streamlined would be to cut out the effort of budding, replicating, and finding its next host.

Which, it seems, viruses have also done.

Called human endogenous retroviruses (HERVs), some viruses have slipped their genetic material into our genome, inserting themselves between host genes or in the long stretches of inaptly named “junk” DNA. Over the course of evolution, these genetic stowaways were passed down to the host’s offspring right alongside genes for blue eyes and attached earlobes. Millions of years later, we find remnants of the viruses encountered by our ancestors written in our DNA like graffiti in a bathroom stall. HERVs comprise as much as 8% of the human genome and some may have integrated into our genomes as long ago as 60-70 million years ago.

Considering the vast changes our genome has undergone in the past 70 million years (by comparison, the human-chimpanzee split occurred only 6 million years ago) it makes sense that the HERVs fossilized in our genome have also been changing. HERVs, like the rest of our genome, acquire DNA mutations at a low but consistent rate. Scientists are able to estimate when a HERV integrated - and by extension, when it was last infectious - by comparing mutations in long terminal repeat (LTR) sequences, stretches of DNA that flank the viral genes like book ends. At the time of integration, these regions are identical, but the longer the HERV has been in the genome, the more mutations the LTRs acquire. By comparing the differences in LTRs flanking HERVs, scientists can estimate how long a HERV has been in the genome.

Previously, the youngest HERVs were estimated to be 800,000 years old. For a recent paper in the journal PLoS ONE that explored how recently HERVs were actually circulating as viruses, Aashish Jha, a University of Chicago graduate student in the Department of Human Genetics and former member of Douglas Nixon’s lab at UCSF, looked for recent integrations into the human genome. Using a genome browser at UCSC, Jha and colleagues tracked all the human-specific, full-length HERVs at a particular place in the human genome. Interestingly, one HERV called k106 didn’t fit the normal timeline.

“It looked interesting because it did not have any mutations in its LTRs,” Jha said.

This was an unusual find, as the age of most HERVs insures at least a few mutations that would aid in dating it. Using genetic information from 51 ethnically diverse individuals, Jha and colleagues were able to estimate that the k106 HERV integrated between 92 and 100 thousand years ago, making it one of the youngest HERVs ever identified.

“This time period is exactly the time modern humans were emerging,” Jha pointed out, “So someone was infected and, given that it was a small population size, it rapidly became fixed in the genome. Then humans moved out of Africa…so even though the virus is new we find it fixed in every human population.”

Having identified this recently integrated, human-specific HERV, it’s possible to gain insight on the ways HERVs have affected the course of our development. LTRs flanking HERVs contain signals that control when and where genes are turned on and off. Placing these viral signals in front of host genes could impact how and when they are expressed and, in some cases, lend an advantage to the individuals possessing it.

“There are multiple ways they [affect evolution],” Jha said.

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The evidence for recent, accelerating global climate change is very strong, as it is for the role we humans have played in influencing our Earth’s weather. But for the most part, there have been few direct tests of how climate change could affect the organisms that inhabit our planet. Much of the evidence on this point is either anecdotal, correlational, or based upon predictive models, such as reports that 1 billion people will be forced to relocate due to climate changes or predictions of increased extinction risk due to changes in temperature, ocean chemistry, sea level, and other factors. None of these studies get at a crucial question that will determine the true impact of these environmental shifts: in a footrace between climate change and evolution, what will win?

Two studies published today in Science suggest an answer for one particular species, the small flowering plant Arabidopsis thaliana. Just as the fruit fly Drosophila melanogaster has become an important tool for scientists studying animal genetics, Arabidopsis is the model organism of choice for studying plant genes. Researchers around the world - including the laboratory of Joy Bergelson, professor and chair of evolution & ecology at the University of Chicago - have characterized the genome of Arabidopsis and looked at the variation within the species.

“Arabidopsis is pretty much ubiquitous; it’s been collected in most parts of the world. You find it throughout Eurasia, Russia, up through Scandinavia and down through the Iberian peninsula,” Bergelson said. “So, as a community, we now we have thousands and thousands of lines from all over, many of which are housed in this lab.”

Those resources allowed Bergelson’s laboratory and another group from Brown University to study the relationship between climate change and evolution in this plant species via two separate experiments. In the first, a team led by University of Chicago postdoctoral researcher Angela Hancock applied the popular methodology of genome-wide association studies (GWAS) to the plant, with a twist. Instead of looking for gene variants associated with a particular characteristic of the plant itself, the team looked for variants associated with different climate variables, such as temperature, precipitation, and humidity. (If it sounds familiar, ScienceLife wrote about a similar study Hancock performed with human genetics in 2010.)

Their analysis produced a list of climate-associated genes that reflect familiar biological processes, controlling aspects of photosynthesis, growth, energy metabolism, and other activities important to plant health. To test whether these genes were truly related to a plant’s fitness in a given climate, the researchers tested their ability to predict how well a plant would grow when grown in one particular climate, that of Lille France, based on the number of favorable variants that they carried. Happily, the gene variants were truly predictive, suggesting that the variants produced by their GWAS indeed played a role in a plant’s ability to grow and reproduce in a given climate.

“You can actually predict pretty decently changes in the relative fitness of plants just based on the results from our worldwide scan,” Bergelson said. “It didn’t have to work - it was a longshot really - but we were happy to see that it did work.”

But for the future of climate change, the more critical question was how these variants initially appeared in the Arabidopsis genome. For many of the climate-associated variants, the University of Chicago team found evidence of “selective sweeps,” an evolutionary process where a new, favorable mutation appears and spreads rapidly through a species. In the case of Arabidopsis, this finding suggests that the plant adapted to shifts in climate thanks to the random appearance and subsequent spread of these helpful mutations, rather than drawing from pre-existing genetic variation. But in times of rapid climate change, there may not be sufficient time to wait for those genetic changes to occur.

“The key there is that the variant is novel, and so the extent to which a plant or an organism depends on sweeps to adapt to climate means that there is an intrinsic delay,” Bergelson said. “As the climate continues to change, they may not have the standing variation that they would need to adapt. That’s going to slow things down.”

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Biology used to be the scientific discipline where data was at a premium, a rare resource painstakingly collected in the field or the laboratory. But today’s biologists are confronted with a flood of data, a fire-hose torrent of genetic and clinical information that only builds with the spread of fast sequencing and electronic medical records. But as these databases fill terabyte after terabyte of computer storage, the successful transformation of that data into practical information about human biology and disease has lagged behind. Genome-wide association studies (GWAS) have  explained only a small percentage of disease heritability, clinical records remain largely unstudied on a large scale, and the complications created by environmental influences and multi-gene disorders have frustrated scientists.

Into this impasse comes a new multi-institutional project based at the University of Chicago: the Silvio O. Conte Center, funded by a nearly $14 million combination of grants from the National Institute of Mental Health and the Chicago Biomedical Consortium. Led by Andrey Rzhetsky, professor of medicine and human genetics at the Medical Center, the collaboration of 15 scientists from 7 institutions will apply the power of advanced computation and data-mining to the growing tide of data collected about neuropsychiatric disorders. The trick will be to not just focus on one database, be it genetics or environmental factors or clinical outcomes, but all of them at once, creating a higher-resolution image of what goes awry in the brain to cause mental disease.

“A great deal of data already exists, yet nobody is already looking at it the way we plan to do and we have very smart people on this team,” said Rzhetsky, who is also a senior fellow of the Computation Institute at the University of Chicago and Institute for Genomics and Systems Biology. “When you have multiple communities that partially study the same subject you can get a kind of three-dimensional picture of a phenomenon.”

Rzhetsky has previously demonstrated the promise of data-mining - the discovery of patterns and information in large pools of data - using clinical records and scientific literature. In a 2007 study, his team examined 1.5 million patient records and found significant overlap between mental disorders such as schizophrenia, bipolar disorder, and autism, suggesting a similar overlap of the genetic factors that cause these conditions. Two years later, Rzhetsky and colleagues applied text-mining computation to the scientific literature database PubMed, creating a network of genes and biological interactions associated with cerebellar conditions such as ataxia and degeneration.

Beyond demonstrating the potential of data-mining, those studies also shed light on the hazy borders separating different psychiatric disorders. While the overlaps could complicate psychiatric diagnosis in the clinic, they might also make the disorders susceptible to the multi-faceted approach proposed by the Conte Center.

“Most studies are done one disorder at a time, and that’s like studying the trunk or the hoof or the tail of an elephant; you might miss the big picture,” said Benjamin Lahey, Irving B. Harris Professor of epidemiology at the University of Chicago and a co-investigator at the Conte Center. “This project will enable us to look at things in a way that has never been done before, at a scale that dwarfs anything that’s ever been done.”

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The University of Chicago can fill a couple of classrooms with all of the Nobel Laureates affiliated with the school, from Milton Friedman to Saul Bellow to Barack Obama. After Monday, a third room might have to be opened up, as Pritzker School of Medicine graduate Bruce Beutler became the 86th member of the exclusive club. Beutler, who graduated from our medical school in 1981, was honored with this year’s Nobel Prize in Physiology or Medicine, along with Jules Hoffman and Ralph Steinman. The three scientists were credited with advancements in the field of immunology that have paved the way for new strategies fighting infections, cancer, and other diseases.

“I thought it was possible, but nobody can count on winning the Nobel Prize, so I’m just ecstatic,” Beutler, now at University of Texas Southwestern Medical Center, told the Chicago Tribune.

In the confusing calculus of the Nobel, Beutler and Hoffman split half of the total award for research on the innate immune system, known as the first line of the body’s defenses against infectious invaders. In the late 1990’s both scientists’ laboratories were looking for immune receptors that respond to signals on the surface of bacteria - Hoffman looking in fruit flies with genetic mutations, Beutler in mice. Within two years of each other, Hoffman discovered a fly mutant named “Toll” involved in the response to an infection, and Beutler found a similar gene in mice for a receptor (named, appropriately, the “Toll-like receptor”) that binds to lipopolysaccharide (LPS), a signal on the surface of bacterial cells.

These findings opened the floodgates to learning about new players in the innate immune system, including the discovery of a dozen more Toll-like receptors that recognize various pathogen signals - what some call “the eyes of the immune system.” Clinically, mutations in these genes can lead to either increased susceptibility to infection (if the innate immune system is too weak) or autoimmune and inflammatory disorders (if the innate immune system is too strong). Drugs that target this system might therefore be promising for the treatment of many different diseases.

“I think the most hopeful line or realm is in inflammatory and autoimmune disease,” Beutler told the Nobel website. “Inflammation is something that evolved to cope with infection, and when we speak of sterile inflammatory diseases like rheumatoid arthritis and autoimmune diseases like lupus, probably some of the same pathways are utilized. It may very well be that by blocking TLR signalling you’ll have very specific therapies for those kinds of diseases.”

Beutler said that he received the news in bed, waking up in the middle of the night and reading an e-mail on his cell phone.

“I was a little bit disbelieving, so I went downstairs to look at my laptop,” Beutler said. “I went to Google News and saw my name there, so I knew it was real.”

At the University of Chicago Medical Center campus, the news quickly spread among former colleagues and teachers of Beutler, as well as scientists that who work in his field.

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