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Researchers receive $500,000 grant to study the “microbiome of death”

Fri, 11/17/2017 - 11:55
Jack Gilbert

Jack Gilbert (Photo: Andrew Collings)

Bacteria surround us everywhere we go. They inhabit every corner of our world, from the places we work and live to the insides of our own bodies. They play an enormous role in our health and well-being, from the development of disease and allergies to how we respond to medicine—and they have the final say in death as well.

Jack Gilbert, faculty director of the Microbiome Center at the University of Chicago, and Gulnaz Javan, a forensic scientist from Alabama State University, received a two-year, $532,000 grant from the National Institute of Justice to study the thanatomicrobiome, or “microbiome of death.” The term was coined by Javan to describe the collection of microbes from internal organs collected during criminal casework. The project will develop tools to help determine the time and cause of death by identifying patterns of bacterial growth in a corpse’s internal organs after death.

Previous work by Gilbert in 2016 showed how bacteria can help pinpoint the time and place of death, but he and Javan also want to see how stress on the body at the time of death leaves a unique signature on microbiota in the organs. The team will work with cadavers from national morgues in Montgomery, Ala., and Pensacola, Fla., plus an international morgue in Tampere, Finland, the largest morgue in that country. They will also explore relationships with morgues in Italy to increase the size and diversity of human corpses and organs that can be studied.

“The aim of this study is to determine whether we can calculate the time of death based on the bacteria that have escaped their normal body habitats and invaded internal organs” Gilbert said. “Once the body dies, the immune system fails and your microbiome is set free – we can track how the microbes migrate by examining the organs of hundreds of bodies.”

The team also hopes to determine if the microbial signature of the organs has any predictive ability when it comes to determining how the individual died.

“We have samples from natural deaths through murders, and we expect to be able to find a signature of how the person died based on the specific bacteria that colonize the organs first,” Gilbert said.

The study will run from January 2018 through December 2019.

Tagged: Biological Sciences, crime investigation, death, decomposition, forensics, Jack Gilbert, Microbiology, microbiome

How a “flipped” gene helped butterflies evolve mimicry

Tue, 11/07/2017 - 11:00
swallowtail butterflies

Several different swallowtail butterfly variations showing mimicry and polymorphism, or different forms of the same species. In the center, a female Papilio polytes that mimics another species that is toxic to predators. (Credit: Matt Wood)

Female swallowtail butterflies do something a lot of butterflies do to survive: they mimic wing patterns, shapes and colors of other species that are toxic to predators. Some – but not all – swallowtail species have evolved several different forms of this trait. But what kind of genetic changes led to these various disguises, and why would some species maintain an undisguised form when mimicry provides an obvious evolutionary advantage?

In a new study published this week in Nature Communications, scientists from the University of Chicago analyze genetic data from a group of swallowtail species to find out when and how mimicry first evolved, and what has been driving those changes since then. It’s a story that started around two million years ago, but instead of steady, progressive changes, one chance genetic switch helped create the first swallowtail mimics. And it has stuck around ever since.

“In butterflies with one color pattern, we have a gene in a normal orientation on the chromosome. In the butterflies with the unusual, alternate color pattern, that gene was spliced out, flipped, and then spliced back into the chromosome at some point,” said Marcus Kronforst, PhD, associate professor of ecology and evolution at UChicago and the senior author of the study.

“That flip, or inversion, keeps the two genes from recombining if those two different kinds of butterflies mate, so they’ve kept both copies of the gene over evolutionary time, since they split from their common ancestor two million years ago,” Kronforst said.

For a long time, scientists thought that butterfly mimicry was controlled by “supergenes,” groups of several tightly linked genes that were always inherited as a group. In a 2014 study, Kronforst and his colleagues showed what appears to be a supergene is actually a single gene called doublesex that controls the different color patterns and shapes we see in female swallowtails.

The doublesex gene was already well-known for its role in differentiating between sexes, but in females the inverted, or flipped, version also dictates wing patterns. It can still be thought of as a supergene because it controls the entire, complex process of wing patterning, but in this case, it is just the single gene.

In the new study, led by postdoctoral fellow Wei Zhang, PhD, the team analyzed whole-genome sequence data form Papilio polytes, the Asian swallowtail butterfly, and several similar species to see how they are related to each other, and how their copies of doublesex compare. Using these data, the team compared some alternative explanations for the origins of mimicry and identified key factors that have maintained different forms of mimicry long-term.

swallowtail butterflies

Several different swallowtail butterfly variations showing mimicry and polymorphism, or different forms of the same species. Row 1: A female and male Papilio protenor, the species that is closely related to Papilo polytes, the focal of the new study. In P. protenor, males and female look the same and they do not mimic. Row 2: Papilio ambrax, a species where males and females look different and the female is a mimic. In this species, there is no female polymorphism. The new study shows that its evolutionary ancestor was polymorphic, but females lost that train and only display the mimetic form. Row 3: Polymorphic Papilio polytes, (L-R) A mimetic female form (one of 3 mimetic forms in this species), a non-mimetic female, and the male. Row 4: A distantly related swallowtail, Pachliopta aristolochiae. This is the toxic species that the species in the new study mimic. (Credit: Matt Wood)

The most closely related species to the P. polytes group, called Papilio protenor, is spread across mainland Asia from India to Japan and did not develop mimicry—both males and females look alike. Other species that spread from the mainland to islands in the Philippines and Indonesia developed three or four distinct forms, a feature known as polymorphism. Still other swallowtail species spread further to Papua New Guinea and the northeast coast of Australia, but those females display only one disguised wing pattern.

The researchers compared the patterns they saw in the genome sequence data to some possible explanations for how these patterns of mimicry developed over time and geography. Did mimicry evolve independently in different species at different points in time? Did it evolve in one species, and then spread through cross-breeding or hybridization?

It appears that mimicry actually has a single ancient origin, when the doublesex gene flipped two million years ago. Since that initial inversion, Zhang and Kronforst did see signs of what’s known as balancing selection. When one type of butterfly becomes more common, predators realize they aren’t toxic and start to feed on them. This reduces the number of that particular butterfly, until another one becomes more common, and so on. Eventually this process balances out and preserves the relative number of each form.

They also saw that some butterfly populations have maintained multiple female forms for millions of years, while others lost the original, undisguised form. Historically, the smallest groups—e.g. the ones that spread the furthest to Australia—lost the polymorphism, allowing random genetic drift and natural selection to weed out the original form.

The researchers also looked at what maintained polymorphism over time. One cause could be sexual selection, that males prefer certain female color patterns over another. Previous research on mating behavior doesn’t back up that idea though. Another possibility is “crypsis,” or the idea that undisguised females blend into their natural surroundings better than the mimics. Kronforst and the team tested that hypothesis by comparing mimetic and non-mimetic females against a green forest background using models for predator (i.e. bird) vision. The non-mimetic, undisguised females actually don’t blend in to the background any more than mimics, so this idea is out too.

swallowtail butterflies

Several different swallowtail butterfly variations showing mimicry and polymorphism, or different forms of the same species. Row 1: A female and male Papilio protenor, the species that is closely related to Papilo polytes, the focal of the new study. In P. protenor, males and female look the same and they do not mimic. Row 2: Papilio ambrax, a species where males and females look different and the female is a mimic. In this species, there is no female polymorphism. The new study shows that its evolutionary ancestor was polymorphic, but females lost that train and only display the mimetic form. Row 3: Polymorphic Papilio polytes, (L-R) A mimetic female form (one of 3 mimetic forms in this species), a non-mimetic female, and the male. Row 4: A distantly related swallowtail, Pachliopta aristolochiae. This is the toxic species that the species in the new study mimic. (Credit: Matt Wood)

Those two findings, combined with the genomic sequence data, led the researchers to start thinking about another intriguing possibility. It could be that the genetic changes that led to mimicry in the first place also built in some long-term disadvantages. When the original doublesex gene inverted, it probably carried a bunch of other unrelated genetic material with it. Since the flipped doublesex gene can’t be recombined with its original version, the extra stuff has “hitchhiked” ever since—and it could have consequences. In fact, some research shows that female mimics don’t live as long as standard ones.

“We think a bunch of differences were accidentally captured when one copy of the gene flipped and became the mimetic copy. Because a lot of those changes are functional, they could be detrimental to health,” Kronforst said.

“The idea is that you have this hardwired disadvantage to mimicry. The standard females don’t have the protection of mimicry, but they also don’t have this inherent genetic cost and these two things offset one another” he said.

Now that they have unraveled some of the history behind the evolution of mimicry, Kronforst said his team wants to start looking for the specific genetic mutations on doublesex that cause different kinds of mimicry.

“If we can find ways to piece through all the differences that we see, we should be able to narrow it down to something much more discrete than all the differences we see now,” he said.

The study, “Tracing the origin and evolution of supergene mimicry in butterflies,” was supported by University of Chicago Neubauer research funds, a Pew Biomedical Scholars Fellowship, the National Science Foundation and the National Institutes of Health. Additional authors include Erica Westerman from the University of Arkansas, along with Eyal Nitzany and Stephanie Palmer from the University of Chicago.

Tagged: Biological Sciences, butterflies, Evolution, Genetics, insects, Marcus Kronforst, mimicry

Mapping the microbiome of… everything

Wed, 11/01/2017 - 13:00

Swabbing bird eggshells from Spain (photo credit: Juan M. Peralta-Sánchez).

In the Earth Microbiome Project, an extensive global team co-led by researchers at University of California San Diego, Pacific Northwest National Laboratory, University of Chicago and Argonne National Laboratory collected more than 27,000 samples from numerous, diverse environments around the globe. They analyzed the unique collections of microbes — the microbiomes — living in each sample to generate the first reference database of bacteria colonizing the planet. Thanks to newly standardized protocols, original analytical methods and open data-sharing, the project will continue to grow and improve as new data are added.

The paper describing this effort, published November 1 in Nature, was co-authored by more than 300 researchers at more than 160 institutions worldwide.

The Earth Microbiome Project was founded in 2010 by Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego; Jack Gilbert, PhD, professor and faculty director of The Microbiome Center at University of Chicago and group leader in Microbial Ecology at Argonne National Laboratory; Rick Stevens, PhD, associate laboratory director at Argonne National Laboratory and professor and senior fellow at University of Chicago; and Janet Jansson, PhD, chief scientist for biology and laboratory fellow at Pacific Northwest National Laboratory. Knight, Gilbert and Jansson are also co-senior authors of the Nature paper and Stevens is a co-author.

“The potential applications for this database and the types of research questions we can now ask are almost limitless,” Knight said. “Here’s just one example — we can now identify what kind of environment a sample came from in more than 90 percent of cases, just by knowing its microbiome, or the types and relative quantities of microbes living in it. That could be useful forensic information at a crime scene… think ‘CSI.’”


Trachypithecus francoisi adult female and infant, a colobine monkey from China, whose fecal microbiome was sampled for this study (photo credit: Kefeng Niu).

The goal of the Earth Microbiome Project is to sample as many of the Earth’s microbial communities as possible in order to advance scientific understanding of microbes and their relationships with their environments, including plants, animals and humans. This task requires the help of scientists from all over the globe. So far the project has spanned seven continents and 43 countries, from the Arctic to the Antarctic, and more than 500 researchers have contributed to the sample and data collection. Project members are using this information as part of approximately 100 studies, half of which have been published in peer-reviewed journals.

“Microbes are everywhere,” said first author Luke Thompson, PhD, who took on the role of project manager while a postdoctoral researcher in Knight’s lab and is currently a research associate at the National Oceanic and Atmospheric Administration (NOAA). “Yet prior to this massive undertaking, changes in microbial community composition were identified mainly by focusing on one sample type, one region at a time. This made it difficult to identify patterns across environments and geography to infer generalized principles.”


Researcher sampling the southernmost geothermal soils on the planet at the summit of Mt Erebus, Ross Island, Antarctica (photo credit: S. Craig Cary, Univ. of Waikato, New Zealand).

Project members analyze bacterial diversity among various environments, geographies and chemistries by sequencing the 16S rRNA gene, a genetic marker specific for bacteria and their relatives, archaea. The 16S rRNA sequences serve as “barcodes” to identify different types of bacteria, allowing researchers to track them across samples from around the world. Earth Microbiome Project researchers also used a new method to remove sequencing errors in the data, allowing them to get a more accurate picture of the number of unique sequences in the microbiomes.

Within this first release of data, the Earth Microbiome Project team identified around 300,000 unique microbial 16S rRNA sequences, almost 90 percent of which don’t have exact matches in pre-existing databases.

Pre-existing 16S rRNA sequence are limited because they were not designed to allow researchers to add data in a way that’s useful for the future. Project co-author Jon Sanders, PhD, a postdoctoral researcher in Knight’s lab compares the difference between these other databases and the Earth Microbiome Project to the difference between a phone book and Facebook. “Before, you had to write in to get your sequence listed, and the listing would contain very little information about where the sequence came from or what other sequences it was found with,” he said. “Now, we have a framework that supports all that additional context, and which can grow organically to support new kinds of questions and insights.”


Hiking through the rain forest of Puerto Rico to sample soils with students (photo credit: Krista McGuire)

“There are large swathes of microbial diversity left to catalogue. And yet we’ve ‘recaptured’ about half of all known bacterial sequences,” Gilbert said.  “With this information, patterns in the distribution of the Earth’s microbes are already emerging.”

According to Gilbert, one of the most surprising observations is that unique 16S sequences are far more specific to individual environments than are the typical units of species used by scientists. The diversity of environments sampled by the Earth Microbiome Project helps demonstrate just how much local environment shapes the microbiome. For example, the skin microbiomes of cetaceans (whales and dolphins) and fish are more similar to each other than they are to the water they swim in; conversely, the salt in saltwater microbiomes makes them distinct from freshwater, but they are still more similar to each other than to aquatic animal skin. Overall, the microbiomes of a host, such as a human or animal, were quite distinct from free-living microbiomes, such as those found in water and soil. For example, the free-living microbiomes were far more diverse, in general, than host-associated microbiomes.

“These global ecological patterns offer just a glimpse of what is possible with coordinated and cumulative sampling,” Jansson said. “More sampling is needed to account for factors such as latitude and elevation, and to track environmental changes over time. The Earth Microbiome Project provides both a resource for the exploration of myriad questions, and a starting point for the guided acquisition of new data to answer them.”


Story provided by the University of California San Diego

For more about the Earth Microbiome Project, visit and follow @earthmicrobiome on Twitter. For the complete list of co-authors and institutions participating in the Earth Microbiome Project, view the full paper at Nature.

The project was funded, in part, by the John Templeton Foundation, W. M. Keck Foundation, Argonne National Laboratory, Australian Research Council, and Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation (ACI-1053575).

Data collected and analyzed in the Earth Microbiome Project have already been used in many studies of:

Tagged: Biological Sciences, earth microbiome project, ecology, ecology and evolution, environment, Jack Gilbert, Microbiology, microbiome

Flu forecasting tool uses evolution to make earlier predictions

Wed, 10/25/2017 - 13:00

Flu shot

Each year, public health officials monitor the spread of influenza to identify which flu strains need to go into that year’s vaccines and where outbreaks will occur. But it can be difficult to predict how bad a particular flu season will be until people actually start getting sick.

A new flu forecasting tool built by scientists at the University of Chicago aims to make better predictions by combining data about how the virus spreads with an estimate of how much the current virus evolved compared to recent years. Using historical data as a test, the new model accurately predicted the total number of cases for each season in the U.S. from 2002 to 2016, and produced an accurate, real-time prediction for the 2016-17 season before it started last year.

The researchers say the new model, described this week in Science Translational Medicine, can be used to complement existing forecasting tools that track flu outbreaks in real time by providing an early warning before the season starts.

“Combining information about the evolution of the virus with epidemiological data will generate disease forecasts before the season begins, significantly earlier than what is currently possible,” said Mercedes Pascual, PhD, professor of ecology and evolution at UChicago and senior author of the study. “You could imagine using our model to make an early prediction about overall severity of the season, and then use other methods to forecast the timing of the outbreak once it begins.”

Each year, four influenza strains circulate in the human population: H3N2, H1N1, and two B variants. These viruses spread seasonally each year because of a phenomenon known as antigenic drift. They evolve just enough to evade human immune systems, but not enough to develop into completely new versions of the virus.

If the virus changed a lot, more people get sick because they haven’t been exposed to that particular variation. But most flu forecasting models don’t factor in this change. Instead, they are based on mathematical calculations of how quickly the virus is spreading—and these projections can’t be made until the current season is already underway.

Factoring in evolution

For the new model, Pascual and Xiangjun Du, PhD, a postdoctoral fellow at UChicago who led the study, analyzed genetic sequences from previous years of the H3N2 virus. They then compared them to early samples of the current virus that were collected before the season started each year. This allowed them to create an evolutionary index for the current virus, or a measure of how much it changed. Adding this crucial piece of information to the new model generates an early estimate of the overall severity of the coming flu season, because they can make a projection as soon as current year’s variation of the virus starts to emerge in the spring and summer.

“Every two or three years, there is a big genetic change in the virus, which can make many more people sick,” Du said. “Without factoring evolution into the model, you cannot capture these peaks in the number of cases.”

The model was built with historical data about the H3N2 virus, although it could be adapted for other strains of flu. The researchers tested its accuracy by seeing how well it predicted past seasons from 2002-2016, including years that weren’t used to initially calibrate the tool (the final five from 2011-2016). It generated accurate estimates of the overall number of cases in the U.S. for each year, and produced an accurate forecast for the 2016-17 season before it started last fall.

So, what’s in store for this flu season?

“That’s the million-dollar question,” Pascual said. “Our analysis for this year showed that the virus is already changing in a significant way. We predict an outbreak that is above average but moderate, not severe, because last year was such a bad season.”

The study, “Evolution-informed forecasting of seasonal influenza A (H3N2),” was supported by the University of Chicago. Additional authors include Aaron A. King and Robert J. Woods from the University of Michigan, who were supported by the National Institutes of Health, the National Institute of General Medical Sciences and the National Institute of Allergy and Infectious Diseases.

Tagged: Biological Sciences, epidemiology, Flu, influenza, Mercedes Pascual, public health, vaccination, Xiangjun Du

What soot-covered, hundred-year-old birds can tell us about saving the environment

Mon, 10/09/2017 - 14:00

Horned Larks collected in Illinois between 1904 and 1916 (left) and California and British Columbia between 1903 and 1922 (right). (Photo: Carl Fuldner and Shane DuBay)

Horned Larks are cute songbirds with white bellies and yellow chins—at least, now they are. One hundred years ago, at the height of urban smoke pollution in the United States, their pale feathers were stained dark gray by soot in the atmosphere.

A new paper in the Proceedings of the National Academy of Sciences shows that the discoloration of these birds in museum collections can be used to trace the amount of black carbon in the air over time and measure the effects of environmental policy on pollution.

“The soot on these birds’ feathers allowed us to trace the amount of black carbon in the air over time,” said study author Shane DuBay, a graduate student in the Committee on Evolutionary Biology at the University of Chicago and The Field Museum. “We found that the air at the turn of the century was even more polluted than scientists previously thought.

DuBay and study co-author Carl Fuldner, a graduate student in the Department of Art History at UChicago, analyzed more than a thousand birds collected over the last 135 years to determine and quantify the effects of soot in the air over cities in the Rust Belt.

“If you look at Chicago today, the skies are blue. But when you look at pictures of Beijing and Dehli, you get a sense for what U.S. cities like Chicago and Pittsburgh were once like,” DuBay said. “Using museum collections, we were able to reconstruct that history.”


Red-headed Woodpeckers from the specimen collection at The Field Museum, Chicago. (Photo: Carl Fuldner and Shane DuBay)

Flying air filters

Ornithologists at The Field Museum have long known that bird specimens in the collection from the early 1900s were visibly darker than expected, and atmospheric soot was the suspect.

“When you touch these birds, you get traces of soot on your hands. We’d wear white gloves while handling them, and the gloves would come away stained, like when you get ink on your fingertips reading a newspaper,” DuBay said, because the soot in the air clung to the birds like dust to a feather duster. “These birds were acting as air filters moving through the environment.”

Birds were also ideal candidates for the study because they molted and grew new sets of feathers every year, meaning that the soot on them had been accumulating only for the past year when they were collected. And there was an apparent trend: old birds were dirtier, and new birds were cleaner.

To measure the changes in sootiness over the years, the pair of researchers turned to a novel approach: photographing the birds and measuring the light reflected off of them. Fuldner, a photo historian who focuses on images of the environment, worked with DuBay to develop a method for analyzing the birds using photography.

Carl Fuldner and Shane DuBay talk about their work in a video from UChicago Arts

The birds photographed for the study, numbering over a thousand, were all from five species that bred in the Manufacturing Belt and have lots of white feathers that show off soot. The images, depicting the contrast between the soiled gray birds and the clean white ones, are dramatic.

“The photographs give the project a visceral dimension—you make a connection to the images,” Fuldner said.

The two researchers plotted the amount of light bouncing off the feathers according to the year the birds were collected. To make sense of their findings, they then delved into the social history of urban air pollution.

“The changes in the birds reflect efforts, first at the city level but eventually growing into a national movement, to address the smoke problem,” Fuldner said. “We are actually able to go back and see how effective certain policy approaches were.”

“We were surprised by the precision we were able to achieve,” DuBay said. “The soot on the birds closely tracks the use of coal over time. During the Great Depression, there’s a sharp drop in black carbon on the birds because coal consumption dropped—once we saw that, it clicked.”

The amount of soot on the birds rebounded around World War II, when wartime manufacturing drove up coal use. Then it dropped off quickly after the war, around when people in the Rust Belt began heating their homes with natural gas piped in from the West rather than with coal.

“The fact that the more recent birds are cleaner doesn’t mean we’re in the clear,” DuBay said. “While the U.S. releases far less black carbon into the atmosphere than we used to, we continue to pump less-conspicuous pollutants into our atmosphere—those pollutants just aren’t as visible as soot. Plus, many people around the world still experience soot-choked air in their cities.”


Field Sparrows collected in Joliet, Ill., in 1906 (top) and Chicago in 1996 (bottom). (Photo: Carl Fuldner and Shane DuBay)

Filling in a blank space in the historical record

Analysis of atmospheric black carbon might assist scientists studying climate change. “We know black carbon is a powerful agent of climate change, and at the turn of the century, black carbon levels were worse than previously thought,” DuBay said. “I hope that these results will help climate and atmospheric scientists better understand the effects of black carbon on climate.”

DuBay and Fuldner initially teamed up through a Graduate Collaboration Grant from the Arts, Science + Culture Initiative at UChicago, which encourages independent trans-disciplinary research between students in the arts and sciences. Both said that being able to apply their research beyond their respective fields of evolutionary biology and photographic history was both unexpected and rewarding.

“As a historian, one of the questions I always ask is, ‘What is the point of this research to the way we live now?’ In this case the answer quickly became clear,” Fuldner said. “Filling in a blank space in the historical record of something as large as air pollution in American cities, and being able to share that with atmospheric scientists who study the effects of black carbon on the climate, is extraordinary.”

“This study shows a tipping point when we moved away from burning dirty coal, and today, we’re at a similar pivotal moment with fossil fuels,” DuBay said. “In the middle of the 20th century, we made an investment in infrastructure and regulated fuel sources—hopefully, we can take that lesson and make a similar transition now to more sustainable, renewable energy sources that are more efficient and less harmful to our environment.”

DuBay notes that in addition to the environmental implications of the project, their work also shows the importance of museum collections like those they used from The Field Museum in Chicago, the Carnegie Museum of Natural History in Pittsburgh, and the University of Michigan Museum of Zoology in Ann Arbor.

“I hope this study exposes collections as a valuable resource to address present day environmental concerns,” he said. “This paper shows the ways that natural history collections can be used, underlining the value in collections and in continuing to build collections, to help us improve our understanding of human impacts on the natural world.”

Story provided by Kate Golembiewski at The Field Museum

Tagged: air pollution, Biological Sciences, birds, carbon emissions, Carl Fuldner, climate change, Field Museum, photography, pollution, Shane DuBay

UChicago scientists receive NIH Director’s high-risk research awards

Thu, 10/05/2017 - 12:01


Three University of Chicago researchers received awards from the National Institutes of Health’s High-Risk, High-Reward Research program. Part of the NIH Common Fund, the program funded 86 awards to exceptionally creative scientists proposing to use highly innovative approaches to tackle major challenges in biomedical research. It supports high-risk ideas with high-impact potential, such as building imaging platforms to monitor genetic processes at a molecular level, identifying immune system proteins that can detect tumors, and creating new chemicals to target genetic factors that lead to disease.

The program accelerates scientific discovery by supporting high-risk research proposals that may not fare well in the traditional peer review process despite their potential to advance the field. Applicants of the program are encouraged to think outside-the-box and to pursue exciting, trailblazing ideas in any area of research relevant to the NIH mission.

“I continually point to this program as an example of the creative and revolutionary research NIH supports,” said NIH Director Francis S. Collins, MD, PhD. “The quality of the investigators and the impact their research has on the biomedical field is extraordinary.”

The NIH Common Fund supports a series of exceptionally high-impact programs that cross NIH Institutes and Centers. Common Fund programs pursue major opportunities and gaps in biomedical research that require trans-NIH collaboration to succeed.

The High-Risk, High-Reward Research program manages four awards. The three UChicago faculty members received the NIH Director’s New Innovator Award, established in 2007, which supports unusually innovative research from early career investigators who are within 10 years of their final degree or clinical residency and have not yet received a research project grant or equivalent NIH grant:

Jingyi Fei, PhDJingyi Fei, PhD

Project Title: Quantitative Imaging of Epitranscriptomic Regulation Mediated by RNA Modification

Jingyi Fei is an Assistant Professor in the Department of Biochemistry and Molecular Biology and the Institute for Biophysical Dynamics at The University of Chicago. Her research has been focused on RNA-mediated gene regulations, including trans-acting small regulatory RNAs in bacterial systems, and RNA internal modifications in eukaryotic systems, with the development and application of new imaging methods.

Seungmin Hwang, PhD

Seungmin Hwang, PhD

Project Title: Targeting by Autophagy Proteins for Anti-Tumor Immunity

Seungmin Hwang is an Assistant Professor in the Department of Pathology at the University of Chicago. The focus of his research group has been understanding the function of the ubiquitin-like conjugation system of the autophagy pathway in sensing and destroying the vacuole-like shelters of intracellular pathogens, expanding this research subject into antitumor immunity.

Raymond Moellering, PhDRaymond Moellering, PhD

Project Title: Targeting Transcription with Synthetic Biologics

Raymond Moellering is an Assistant Professor in the Department of Chemistry at the University of Chicago. He started his independent research program at UChicago in 2015, where his laboratory is focused on developing new chemical tools and technologies to study complexity and dynamics in the proteome, thus illuminating causal pathways in disease as well as novel therapeutic strategies to target them.

For 2017, NIH issued 12 Pioneer awards55 New Innovator awards8 Transformative Research awards, and 11 Early Independence awards. The 2017 awards total approximately $263 million, pending available funds, and represent contributions from the NIH Common Fund; National Institute of General Medical Sciences; National Institute of Mental Health; National Center for Complementary and Integrative Health; and National Institute of Dental and Craniofacial Research.

Story provided by the NIH

Tagged: biochemistry, Biological Sciences, Cancer, chemistry, Genetics, Jingyi Fei, molecular biology, NIH, pathology, Ray Moellering, research funding, Seungmin Hwang

It’s a cinch: Multiplication by division via the actomyosin ring

Tue, 09/26/2017 - 09:00

The contractile actomyosin ring, illuminated in the center of these yeast cells, is a belt-like structure that (most) dividing cells assemble at the center during the final stage of cell division. It constricts the mother cell and separates it into two daughter cells.

The final stages of the fundamental process of cell division are driven, in most cases, by a contractile actomyosin ring, but little is known about how this ring gets assembled or performs its role. Science Life spoke with post-doctoral fellow Dennis Zimmermann, PhD – in the laboratory of David Kovar, PhD, Professor of Molecular Genetics and Cell Biology, and of Biochemistry and Molecular Biology. They were the first and senior authors of a study published September 26, 2016, in Nature Communications.

Their project, “Mechanoregulated inhibition of formin facilitates contractile actomyosin ring assembly,” describes the underlying molecular principles that govern the highly coordinated assembly of the contractile actomyosin ring during cell division. Zimmerman is now an independent research fellow at the Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research.

What is a contractile actomyosin ring?

The contractile actomyosin ring is a belt-like structure that (most) dividing cells assemble at the cell equator after chromosome separation during the final stage of cell division. The contractile ring plays a crucial role in most dividing animal cells. It constricts the mother cell, thereby mediating the physical separation into two daughter cells.

What is actomyosin, and what is formin?

Actomyosin describes filamentous actin network structures that interact with myosin motor proteins. This provides these networks with the ability to produce forces powerful enough to work against the internal turgor pressure of a dividing cell. The contractile ring is only one of many different actomyosin networks. The classical example is a muscle sarcomere where myosin motors and actin make up the core contractile unit of a muscle fiber.

Formins describe a conserved family of actin-binding proteins that have evolved to drive the continuous assembly of long straight actin filaments.


Dennis Zimmerman, PhD, postdoctoral fellow in molecular genetics and cell biology

Why and how do you study this in yeast?

The actin cytoskeleton is a versatile, complex machinery that encompasses many different components. Each one carries out its own specific function at the right time and place. Human cells can assemble more than 20 different actin networks, employing dozens of different actin-binding proteins. The formin family in humans, for example, comprises more than 15 members.

In contrast, the unicellular fission yeast (Schizosaccharomyces pombe) has been serving as a popular model organism because it assembles only three main actin networks, while encoding only three different formins. Working with this reduced set of cytoskeletal actin network components, we are able to manipulate and visualize specific sets of actin-binding proteins (e.g. formins) with relative ease.

The parts list of actin-binding proteins involved in building the fission yeast contractile ring have been identified in previous studies. It is still unclear, however, how the different factors collaborate and regulate each other at the molecular level in order to facilitate proper ring assembly.

Therefore, we set out to reconstitute in vitro (i.e. to rebuild outside the cell) the previously proposed model of contractile ring assembly using purified and fluorescently labeled versions of the essential ring components: actin, formin and myosin. Using specialized multi-color microscopy (a total internal reflection fluorescence microscope), we were able to study the behavior of individual formin molecules that are bound to an elongating actin filament that at the same time experiences pulling forces by engaging myosin motors. We also used confocal fluorescence microscopy of live fission yeast cells containing fluorescently labeled versions of the same proteins to validate the relevance of our in vitro findings in vivo.

Can you explain – at a very basic level – how this process works?

In this study, we demonstrate the first minimal component reconstitution of the Search-Capture-Pull model for contractile ring assembly.

In this model, formins, anchored to ring precursor structures at the cell membrane, assemble ‘searching’ actin filaments using the cytoplasmic pool of actin filament building blocks, while remaining continuously associated with the elongating actin filament. Class II myosin motors then ‘capture’ the ‘searching’ filament and ‘pull’ on the filament, thereby bringing neighbouring ring precursor structures closer together.

This behaviour has never been recapitulated in vitro, so the underlying molecular mechanisms and ensemble properties of components facilitating node condensation were unknown.

We discovered that the application of minute (sub-piconewton) forces by the physiological force generator myosin Myo2 to formin Cdc12-bound actin filaments results in the reversible mechano-inhibition of Cdc12’s ability to polymerize actin filaments. Mechanistically, we identified the formin domain that relays the force-sensitive response. Quantitative modelling suggests that those small forces may suffice to stretch the force-sensitive domain, which in turn impedes formin-mediated actin filament elongation. Finally, live cell imaging of mechano-insensitive formin mutant cells established that mechano-inhibition of formin Cdc12 is required to effectively condense contractile ring precursors, thereby enabling efficient cytokinesis in vivo.

What parts of the process can go awry?  What damage can that do?

One of the most critical points during cell division is ensuring proper chromosome segregation. This step precedes ring formation and is tightly regulated. Cells do not enter the final phase of cell division, during which ring assembly occurs, until chromosome separation has occurred. This is a crucial step in obtaining two healthy progenitor cells. Improper ring constriction can cause chromosome mis-segregation, which leads to dysfunction or cell death.

How does the cell prevent that?

The different ways in which cells prevent improper ring assembly have been under extensive investigation for years. Some questions have been answered; even more have arisen. One crucial part of proper ring assembly and successful cell division is the correct placement of the so-called cleavage site, the point at which the actual contractile ring will assemble and constrict.

This process is largely determined by signaling pathways that drive the initial localization and activation of various ring components. What is less well understood is how components like myosin and formin are regulated once activated. This is what motivated us to study the underlying molecular mechanisms acting during the assembly of the contractile actomyosin ring.

Formin’s role involves mechanical force rather than chemical signaling.  How do these processes co-exist?

I think chemical signaling and the influence of mechanical force almost always co-exist. Therefore, the question is not so much how these two kinds of modes of regulation co-exist, but how do they impact and counter-balance each other. This opens up a whole new and exciting layer of regulation that requires further investigation.

Here’s one way to think of it. Chemical signaling cues often initiate (or terminate) specific responses. They set the stage for a specific process that’s about to happen. Mechanical forces, on the other hand, provide the cell with an adjustable dial-like tool through which a given response can be tuned to accommodate ever-changing cellular constraints.

How significant, as a rule, is mechanical as compared to chemical force?

They are co-dependent. Both signaling-mediated and mechano-regulated forces must co-exist to ensure the functionality of a given cellular process under physiological conditions.

Which other important cellular processes rely on mechanotransduction?

Quite a few. This is widespread. Examples would include cell adhesion, motility and migration, tissue development, wound healing. This area of biological inquiry will keep us busy for a long time.

The United States Department of Defense, the German Research Foundation and the National Institutes of Health supported the research. Additional authors include Kaitlin Homa, Glen Hocky and Gregory Voth from the University of Chicago; Luther Pollard and Kathleen Trybus from the University of Vermont; and Enrique De La Cruz from Yale University.

Tagged: Biological Sciences, cell biology, cell division, David Kovar, Dennis Zimmerman, Genetics, molecular biology, molecular genetics

Single gene controls variety of wing patterns across butterfly species

Mon, 09/18/2017 - 14:00

Monarch butterflies studied by Marcus Kronforst and Darli Massardo at the University of Chicago. The white patches on the wings, most prominent on the bottom left and middle right specimens, show where the WntA gene was knocked out and did not produce the characteristic orange scales. (Credit: Matt Wood, University of Chicago)

A single gene is responsible for producing different wing patterns, shapes and colors across several butterfly species, scientists report this week in a new study published in the Proceedings of the National Academy of Sciences.

Using CRISPR/Cas9 gene editing tools, researchers from seven institutions knocked out a gene called WntA in embryos from seven different butterfly species, essentially turning it off. The resulting adult butterflies developed changes in wing patterns and colors that differed in each species, suggesting that while WntA plays a fundamental role in wing patterning across butterfly species, it has been used in a variety of ways.

“Every butterfly has a unique color pattern and there is extraordinary diversity among species, but they’re not reinventing the wheel when it comes to developing those unique color patterns,” said Marcus Kronforst, PhD, associate professor of ecology and evolution at the University of Chicago and an author on the study. “In the case of WntA, they’re using that one gene again and again and again.”

Video: University of Chicago researcher Darli Massardo explains how knocking out the WntA gene changes the coloring of orange scales on monarch buttefly wings. (Credit: Kat Carlton, University of Chicago)

Previous genetic studies have identified WntA as the gene that controls patterns of melanin, or dark pigmentation, in the wings of Heliconius butterflies. The widespread group of species lives throughout the tropical and subtropical regions of North and South America. Other studies have also pinpointed the role of WntA in wing patterning of other groups, suggesting that it is widely conserved across all butterfly species.

Until recently, however, scientists lacked the tools to directly test of function of this gene in butterflies. For the new study, coordinated by Arnaud Martin from the George Washington University, each research team from seven different institutions chose a different butterfly species and used the CRISPR gene editing system to knock out WntA.

Kronforst and Darli Massardo, PhD, a postdoctoral fellow at UChicago, worked with monarch butterflies. The loss of WntA caused the monarch’s characteristic orange scales to turn white, but didn’t change the overall pattern of the wings. Another team worked with painted lady butterflies, which lost the usual black spots in the middle of their wings. Other species developed differently shaped bands across the wings.


University of Chicago researchers Darli Massardo and Marcus Kronforst in the greenhouse on top of the Donnelly Biological Sciences Learning Center on the University of Chicago campus. (Credit: Kat Carlton, University of Chicago)

“When we knock out the gene, we’re seeing totally different effects,” Massardo said. “So, although WntA is involved in wing-patterning in general, it’s doing fundamentally different things in different species.”

Kronforst and Massardo say that the results of this study give scientists insight into the process of evolution, as butterflies exploit the utility of this gene to develop multiple wing patterns. The widespread use of precise genetic tools like CRISPR will allow them to explore this process further, moving beyond simple knockout experiments to more complex, functional changes.

“Now we’re just altering the gene to make it nonfunctional,” Kronforst said. “But what we’d really like to do are things like precisely put in a copy of the same gene from another species or another color pattern and see what that does. This just opens the door for us.”


Monarch butterflies in the greenhouse on top of the Donnelly Biological Sciences Learning Center on the University of Chicago campus. (Credit: Kat Carlton, University of Chicago)

The study, “Macro-evolutionary shifts of function potentiate butterfly wing pattern diversity,” was supported by the National Science Foundation, the National Institutes of Health, the Leverhulme Trust, the Pew Charitable Trust, a Nigel Groome PhD studentship and the Smithsonian Institution. Additional authors include Anyi Mazo-Vargas, Linlin Zhang and Robert Reed from Cornell University; Carolina Concha from North Carolina State University; Luca Livraghi and Casper Breuker from Oxford Brookes University; Richard Wallbank and Chris Jiggins from the University of Cambridge; Joseph Papador, Daniel Martinez-Najera and Nijam Patel from the University of California, Berkeley; and W. McMillan from the Smithsonian Tropical Research Institute.

Tagged: Biological Sciences, butterflies, CRISPR, Darli Massardo, ecology, Evolution, genetic engineering, Genetics, Marcus Kronforst, monarch butterflies
WntA butterflies

Antibiotics weaken signs of Alzheimer’s disease in mice after just one week of treatment

Fri, 09/15/2017 - 09:00
Minter Sisodia

Neurobiologists Myles Minter, PhD, left, and Sangram Sisodia, PhD

Last year, UChicago neurobiologists Sangram Sisodia and Myles Minter made a surprising discovery: Treating mice with antibiotics long-term reduced some of the telltale signs of Alzheimer’s disease.

Mice that received high doses of broad spectrum antibiotics over five to six months had a two-fold decrease in amyloid-ß (Aß) peptides in the brain, the “plaques” or that build up and play a central role in the onset of Alzheimer’s. They also had altered inflammation of microglia, brain cells that perform immune system functions in the central nervous system.

Of course, this doesn’t mean antibiotics could be a “treatment” for Alzheimer’s disease. There may be changes occurring in the brain and central nervous system 15 to 20 years before diagnosis, and administering antibiotics for more than a few weeks to treat an infection is a bad idea anyway. But what was intriguing about that study is what it suggested about how microbes might be interacting with the brain and nervous system.

When the team analyzed the gut bacteria of the mice, they saw dramatic changes in the overall diversity of the community of microbes. Some species of bacteria were wiped out, while others thrived. A growing body of research shows how gut bacteria interact with the immune system and brain through the periphery of the nervous system. Sisodia and Minter believe that the changes they saw in the microbiome of these mice could somehow be linked to the changes in the brain—and a new study shows that the timing of when antibiotics are given may mean everything.

In a new study just published in Scientific Reports, they performed similar experiments, but instead of giving the mice antibiotics long-term, they did it for just one week when the mice were only two weeks old. The results, again, were surprising: They saw all the same changes in Aß plaques, microglia activity and gut bacteria diversity, although to a slightly lesser extent.

“The most staggering part for me was after giving one week of antibiotics very early on, we see the expansion and contraction of various strains of bacteria,” said Minter, who is a postdoctoral scholar. “But the fact that it seems to be the developmental window that can have these long-lasting effects in this mouse model is pretty exciting, and something we certainly weren’t expecting.”

Video: Sangram Sisodia and Myles Minter talk about the relationship between the microbes living in your gut and your brain, for Argonne’s Microbiome Project.

This early developmental period is believed to be crucial for the proper development of the gut microbiome, and an early blow can lead to long-term consequences. For example, earlier this year, Eugene Chang’s team showed that giving antibiotics to mice during pregnancy can increase the risk for their offspring developing a form of inflammatory bowel disease.

These changes can go both ways though. In 2015, Cathy Nagler and her team showed that probiotic formula for babies can help reverse allergies to cow’s milk by replacing certain gut bacteria.

Sisodia said that his team’s work paves the way for more experiments to understand the exact mechanisms behind how the changes in gut microbes might be related to changes in microglial nerve cells and their ability to clear plaques. Minter is working on genetic experiments to understand the molecular changes taking place that could be affecting signals between gut bacteria and the immune and nervous systems, and the group is looking at more ways the timing of antibiotics play a role as well.

“We need to design experiments where we treat animals later in life, either before they develop amyloid deposits or right about the time they do,” said Sisodia, the Thomas Reynolds Sr. Family Professor of Neurosciences. “In Alzheimer’s, the ability to clear amyloid plaques is reduced. We think microglia play a central role in that, and we want to identify what could be changing in their metabolism early in life that could be priming these cells to do their job.”

Tagged: Alzheimer's, Alzheimer's disease, antibiotics, Biological Sciences, microbiome, Myles Minter, neurobiology, Neuroscience, Sangram Sisodia

UChicago scientists create alternate evolutionary histories in a test tube

Wed, 09/13/2017 - 12:00

University of Chicago graduate student Tyler Starr holds a vial of yeast cells engineered with a library of proteins comprising millions of possible evolutionary paths from our ancient ancestor to its modern function. (Credit: Matt Wood, University of Chicago)

Scientists at the University of Chicago studied a massive set of genetic variants of an ancient protein, discovering a myriad of other ways that evolution could have turned out and revealing a central role for chance in evolutionary history.

The study, published this week in Nature by University of Chicago graduate student Tyler Starr and his advisor Professor Joseph Thornton, PhD, is the first to subject reconstructed ancestral proteins to deep mutational scanning — a state-of-the-art technique for characterizing massive libraries of protein variants.  The authors’ strategy allowed them to compare the path that evolution actually took in the deep past to the millions of alternative routes that could have been taken, but were not.

Starting with a resurrected version of an ancient protein that evolved a new function some 500 million years ago – a function critical to human biology today — the researchers synthesized a massive library of genetic variants and used deep mutational scanning to analyze their functions.  They found more than 800 different ways that the protein could have evolved to carry out the new function as well, or better than, the one that evolved historically.

The researchers showed that chance mutations early in the protein’s history played a key role in determining which ones could occur later.  As a result, the specific outcome of evolution depended critically on the way a serial chain of chance events unfolded.

“By comparing what happened in history to all the other paths that could have produced the same result, we saw how idiosyncratic evolution is,” said Starr, a graduate student in biochemistry and molecular biology, who performed the paper’s experiments. “People often assume that everything in biology is perfectly adapted for its function.  We found that what evolved was just one possibility out of many that were just as good, or even better, functionally than what we happened to end up with today.”

Molecular time travel

Over the last 15 years, Thornton, senior author on the new study and a professor of ecology and evolution and human genetics at UChicago, led research that pioneered “molecular time travel” using ancestral protein reconstruction.  In 2013, his team resurrected and analyzed the functions of the ancestors of a family of proteins called steroid hormone receptors, which mediate the effects of hormones like testosterone and estrogen on sexual reproduction, development, physiology, and cancer.  The body’s various receptors recognize different hormones and, in turn, activate the expression of different target genes, which they accomplish by binding specifically to DNA sequences called response elements near those targets.

Thornton’s group inferred the genetic sequences of ancient receptor proteins by statistically working their way back down the tree of life from a database of hundreds of present-day receptor sequences. They synthesized genes corresponding to these ancient proteins, expressed them in the lab, and measured their functions.

They found that the ancestor of the family behaved like an estrogen receptor – recognizing only estrogens and binding to estrogen response elements – but during one specific interval of history, they evolved into a descendant group capable of recognizing other steroid hormones and binding to a new class of response elements. The researchers found that three key mutations before the emergence of vertebrate animals caused the ancestral receptor to evolve its ability to bind to the new target sequences.

That work set the stage for the current study.  Knowing precisely how evolution played out in the past, Thornton’s group asked: Was this the only evolutionary path to evolving the new function? Was it the most effective one, or the easiest to achieve?  Or was it simply one of many possibilities?


Graduate student Tyler Starr works in a lab at the University of Chicago Gordon Center for Integrative Science. (Credit: Matt Wood, University of Chicago)

Alternate histories

Starr began working on the project during his first year as a graduate student, developing the technique to assess massive numbers of variants of the ancestral receptor for their ability to bind the new response element.  First, he engineered strains of yeast in which the ancestral or new response elements drive expression of a fluorescent reporter gene.  He then synthesized a library of ancestral proteins containing all possible combinations of amino acids at the four key sites in the receptor that recognize DNA – 160,000 in all, comprising all possible evolutionary paths that this critical part of the protein could have followed – and introduced this library into the engineered yeast.  He sorted hundreds of millions of yeast cells by their fluorescence using a laser-driven device, and then used high-throughput sequencing to associate each receptor variant with its ability to carry out the ancestral function and the new function.

Most of the variants failed to function at all, and some maintained the ancestral function.  But Starr found 828 new versions of the protein that could carry out the new function as well, or better than, the one that evolved during history.  Remarkably, evolution could have accessed many of these even more easily than the historical “solution,” but it happened not to, apparently wandering around the space of possible mutations until it arrived at the version of the protein in our bodies today.

Joe Thornton, PhD

Joe Thornton, PhD

“We all share the same gene sequence for this protein, so it might seem like evolutionary destiny, as if we’ve arrived at the best possible version.  But there are hundreds of other directions that evolution could just as well have taken,” Thornton said.  “There’s nothing special about the history that happened, except that a few chance steps brought us to this singular chance outcome.”

Thornton said that deep mutational scanning will be a powerful tool for evolutionary biologists, geneticists and biochemists, and he looks forward to using the approach on successive ancestors at different points in history to see how the set of possible outcomes changed through time.

“We have a molecular time machine to go back to the past, and once we’re there, we can simultaneously follow every alternate history that could possibly have played out,” Thornton said. “It’s a molecular version of every evolutionary biologist’s dream.”

The study, “Alternate evolutionary histories in the sequence space of an ancient protein,” was supported by the National Institutes of Health and the National Science Foundation. Lora Picton, a former research scientist in Thornton’s lab at the University of Chicago, was also co-author.

Tagged: biochemistry, Biological Sciences, Evolution, Genetics, Joe Thornton, molecular biology, proteins, Tyler Starr

Systems analysis points to links between Toxoplasma infection and common brain diseases

Wed, 09/13/2017 - 09:48

The protozoan Toxoplasma gondii, tissue cyst in brain (Photo: D. Ferguson, Oxford University)

More than 2 billion people – nearly one out of every three humans on earth, including about 60 million people in the United States – have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii.

In the September 13, 2017, issue of Scientific Reports, 32 researchers from 16 institutions describe efforts to learn how infection with this parasite may alter, and in some cases amplify, several brain disorders, including epilepsy, Alzheimer’s and Parkinson’s diseases as well as some cancers.

When a woman gets infected with T. gondii during pregnancy and passes the parasite on to her unborn child, the consequences can be profound, including devastating damage to the brain, nervous system and eyes.

There is growing evidence, however, that acquiring this infection later in life may be far from harmless. So the researchers began looking for connections between this chronic but seemingly dormant infection and its potential to alter the course of common neurologic disorders.

“We wanted to understand how this parasite, which lives in the brain, might contribute to and shed light on pathogenesis of other brain diseases,” said Rima McLeod, MD, professor of ophthalmology & visual science and pediatrics and medical director of the Toxoplasmosis Center at the University of Chicago.

Rima McLeod, MD

Rima McLeod, MD

“We suspect it involves multiple factors,” she said. “At the core is alignment of characteristics of the parasite itself, the genes it expresses in the infected brain, susceptibility genes that could limit the host’s ability to prevent infection, and genes that control susceptibility to other diseases present in the human host. Other factors may include pregnancy, stress, additional infections, and a deficient microbiome. We hypothesized that when there is confluence of these factors, disease may occur.”

For more than a decade, researchers have noted subtle behavior manipulations associated with a latent T. gondii infection. Rats and mice that harbor this parasite, for example, lose their aversion to the smell of cat urine. This is perilous for a rodent, making it easier for cats to catch and eat them. But it benefits cats, who gain a meal, as well as the parasites, who gain a new host, who will distribute them widely into the environment. An acutely infected cat can excrete up to 500 million oocysts in a few weeks’ time. Even one oocyst, which can remain in soil or water for up to a year, is infectious.

A more recent study found a similar connection involving primates. Infected chimpanzees lose their aversion to the scent of urine of their natural predator, leopards.

The research team decided to search for similar effects in people. They focused on what they call the human “infectome” – plausible links between the parasite’s secreted proteins, expressed human microRNAs, the neural chemistry of the human host, and the multiple pathways that are perturbed by host-parasite interactions.

Using data collected from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study, which has diagnosed, treated and followed 246 congenitally infected persons and their families since 1981, they performed a “comprehensive systems analysis,” looking at a range of parasite-generated biomarkers and assessing their probable impact.

Working with the J Craig Venter Institute and the Institute of Systems Biology Scientists, they looked at the effect of infections of primary neuronal stem cells from the human brain in tissue culture, focusing on gene expression and proteins perturbed. Part of the team, including Huan Ngo from Northwestern University, Hernan Lorenzi at the J Craig Venter Institute, Kai Wang and Taek-Kyun Kim at the Institute for Systems Biology and  McLeod, integrated host genetics, proteomics, transcriptomics and circulating microRNA datasets to build a model of these effects on the human brain.

Using what they called a “reconstruction and deconvolution,” approach, the researchers identified perturbed pathways associated with neurodegenerative diseases as well as connections between toxoplasmosis, human brain disorders and some cancers.


T. gondii (I, II, III) infection of S-NSC alters localization of p50-NFkB(red) and Stat 3 (second panel, red): SAG1 (Green), Hoechst (blue); T. gondii, in NSC, expresses or alters host cells’ neurotransmitters. Tyrosine Hydroxylase (red) in the infected NSCs that synthesizes dopamine is present in T. gondii (middle panels 40X, 60X). This is further exemplified in the furthest right panel by a dopamine-like immunostaining pattern in the parasite (green). The red arrow in the dopamine-like staining image points to a host cell dense perinuclear distribution of label. This suggests potential to influence neurotransmission in human NSC.

They also found that:

  • Small regulatory biomarkers – bits of microRNA or proteins found in children with severe toxoplasmosis – matched those found in patients with neurodegenerative diseases like Alzheimer’s or Parkinson’s disease.
  • The parasite was able to manipulate 12 human olfactory receptors in ways that mimicked the cat-mouse or the chimp-leopard exchange.
  • Evidence that gondii could increase the risk of epilepsy, “possibly by altering GABAergic signaling.”
  • gondii infection was associated with a network of 1,178 human genes, many of which are modified in various cancers.

“Our results provide insights into mechanisms whereby this parasite could cause these associated diseases under some circumstances,” the authors wrote. “This work provides a systems roadmap to design medicines and vaccines to repair and prevent neuropathological effects of T. gondii on the human brain.”

“This study is a paradigm shifter,” said co-author Dennis Steinler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “We now have to insert infectious disease into the equation of neurodegenerative diseases, epilepsy and neural cancers.”

“At the same time,” he added, “we have to translate aspects of this study into preventive treatments that include everything from drugs to diet to life style, in order to delay disease onset and progression.”

This work was funded by the National Institutes of Health, the Mann Cornwell Family, the Engel family, the Rooney, Drago, and the Morel families, and “Taking out Toxo.” The Institute for Systems Biology is partially supported by research contracts from the Defense Threat Reduction Agency and the Department of Defense. The J. Craig Venter Institute sequencing and analysis was funded by the National Institute of Allergy and Infectious diseases, as was parts of the work at the University of Chicago.

Additional authors include Ying Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Fiona L. Henriquez, Kelsey Wheeler, Ian Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez and Shawn Withers from the University of Chicago; Huan Ngo, Gwendolyn Noble and Charles N. Swisher from Northwestern University; Hernan Lorenzi and Seesandra V. Rajagopala from the Craig Venter Institute; Kai Wang, Taek-Kyun Kim, Yong Zhou and Leroy Hood from the Institute of Systems Biology, Seattle; Craig W. Roberts from the 6University of Strathclyde, Glasgow; Alexandre Montpetit from Genome Quebec, Montréal, Canada; Jenefer Blackwell from McGill University; Sarra Jamieson from the University of Western Australia; Roderick Davis from the University of Illinois-Chicago, Liliana Soroceanu from California Pacific Medical Center, Charles Cobbs from Tufts University, Kenneth Boyer and Peter Heydemann from Rush University Medical Center, Chicago; Peter Rabiah from Northshore University Health System, Evanston, IL; and Patricia Soteropoulos from Rutgers University.

Tagged: Alzheimer's disease, Biological Sciences, epilepsy, Infectious Disease, neurology, Neuroscience, parasites, Parkinson's disease, Rima McLeod, toxoplasmosis

Graduate students in biological sciences attend computation bootcamp

Mon, 09/11/2017 - 16:14

UChicago students Matt Trendowski and Hallie Sussman attend the Biological Sciences Division bootcamp. (Photo byMegan Costello)

As biology increasingly transforms into a discipline driven by ever-expanding datasets and computational analysis, students need new forms of training to follow best practices and build a successful research career. With a new award from the National Science Foundation, the University of Chicago Biological Sciences Division will test an innovative curriculum, which it piloted at the Marine Biological Laboratory, that focuses on hands-on learning in computational methods and how to use these tools in a rigorous and reproducible way.

For a week before their first courses begin, incoming graduate students from every BSD graduate program will travel to Marine Biological Laboratory in Woods Hole, Mass. for a weeklong “bootcamp” session. This training experience—combined with a responsible research course taught later in the academic year—will prepare students with the programming, statistics and documentation practices needed to produce cutting-edge science.

Read more about the bootcamp at UChicago News.

Tagged: big data, Biological Sciences, biostatistics, computation, computer programming, computer science, Marine Biological Laboratory, statistics

UChicago researcher receives Fulbright award to study toxoplasmosis in Morocco

Thu, 08/24/2017 - 09:00


Kamal El Bissati, PhD, a faculty member in the department of Ophthalmology and Visual Sciences at the University of Chicago, has been awarded a Fulbright U.S. Scholar Award in Medical Sciences and Public/Global Health for 2017-2018.

El Bissati is a microbiologist who studies how parasites that cause diseases interact with their hosts, specifically toxoplamosis. Toxoplasmosis is a serious, potentially fatal parasitic disease. While some people carry the Toxoplasmosis gondii parasite without showing any symptoms, it can cause blindness, developmental disabilities and epilepsy in infants born to mothers infected with it.

Toxoplasmosis is a serious issue in the developing world, including Bissati’s native Morocco, where as many as half of pregnant women carry the parasite. Under the Fulbright program, he will travel to Morocco for the 2017-18 academic year to collect genetic variation data on the parasite in North Africa to support his ongoing research with Rima McLeod, MD, Medical Director of the Toxoplasmosis Center at UChicago and one of the world’s leading experts on the disease.

The Fulbright Program is the flagship international educational exchange program sponsored by the U.S. government. Each year more than 800 U.S. citizens teach, conduct research, and provide expertise abroad in over 160 countries worldwide.

Read more about Kamal El Bissati’s research here on Science Life.

Tagged: Biological Sciences, Fulbright, Fulbright Scholar Program, Global Health, Infectious Disease, Kamal El Bissati, Microbiology, morocco, toxoplasmosis

Scientists identify gene that controls immune response to chronic viral infections

Tue, 08/15/2017 - 11:00

Image: Immunity

For nearly 20 years, Tatyana Golovkina, PhD, a microbiologist, geneticist and immunologist at the University of Chicago, has been working on a particularly thorny problem: Why are some people and animals able to fend off persistent viral infections while others can’t?

Mice from a strain called I/LnJ are especially good at this. They can control infection with retroviruses from very different families by producing specific antibodies that coat viruses and render them innocuous.

Golovkina, a Professor of Microbiology, was interested in what makes these mice special, so she began searching for the genes responsible for their remarkable immune response. In a new study published this week in the journal Immunity, she and her colleagues identify this gene. They also began to uncover more clues how it might work to control anti-virus immune responses.

Using a process called positional cloning, in which researchers progressively narrow down the location of a gene on the chromosome, they pinpointed it within the major histocompatibility complex (MHC) locus. The MHC locus is a well-known region of the genome involved with the immune system so it makes sense that the gene was located there, but this was a disconcerting discovery.

“It was a bummer at first because there are tons of genes within the MHC locus all controlling immune response, not only against viruses, but also many other microbial pathogens and non-microbial disorders,” she said. “Most of the time when people map a gene to the MHC they give up and stop there, with an assumption that the gene encodes for one of the two major MHC molecules, MHC class I or and MHC class II.”

But with the help of a biochemist, Lisa Denzin from Rutgers University, and a computational biologist, Aly Khan from the Toyota Technological Institute at Chicago, Golovkina and her team identified a gene called H2-Ob that enables this resistance. Together with another gene called H2-Oa, it makes a molecule called H2-O in mice and HLA-DO in humans.

H2-O has been known for years as a negative regulator of the MHC class II immune response, meaning that it shuts down the immune response. Most researchers thought it was there to prevent autoimmune responses, which attack the body’s own tissues. But in this case, none of the I/LnJ mice showed signs of autoimmunity, so H2-O must have another purpose.

Golovkina and her team discovered another interesting thing when they crossed I/LnJ mice that were resistant to infections with ones that were more susceptible. The resultant F1 mice were susceptible to infection. This indicated that the I/LnJ H2-Ob gene was recessive; both parents had to have a copy of the mutated gene to pass it on their offspring, and the product of the gene should be a non-functional protein.

Tanya Golovkina

Tanya Golovkina, PhD

“That was really surprising,” Golovkina said. “Almost all pathogen-resistant mechanisms discovered so far are dominant, meaning that something needs to be gained to resist.”

The immune system response to a virus in susceptible mice lasts three to four weeks, then the H2-O molecule tells it to stop. But the I/LnJ mice, which respond vigorously to infections, have a mutation on H2-Ob that makes it inactive. So, after they launch an immune response, it never shuts off. This keeps persistent retroviruses in check.

Golovkina hypothesizes that while letting the immune response keep running may keep chronic infections in check, such as retroviruses or hepatitis B and C, other pathogens like tuberculosis can take advantage of a persistent immune response because they can get access to certain cells when they’re coated with antibodies (and I/LnJ mice happen to be susceptible to TB and produced anti-TB antibodies).

At some point during the evolution of these genes, it was more advantageous to be able to switch off the immune response to some infections (such as intracellular bacterial pathogens), but it came at the cost of not being able to fight other long-term infections.

Now that her team has identified the gene underlying anti-retrovirus and potentially anti-hepatitis B and C responses, Golovkina says that further research should be done to create genetic therapies to manipulate the function of this gene, or develop molecules that could interfere with the function of H2-O to allow the virus-specific response in chronically infected people.

Until then, she’ll continue working on this problem, just as she has for the past 20 years.

“I have a very persistent nature in the way I do research,” she said. “If I sincerely believe there is a very interesting biological question, nothing will prevent me from uncovering it.”

The study, “Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob,” was supported by the United States Department of Health and Human Services, the National Institutes of Health and the Robert Wood Johnson Foundation. Additional authors include Francesca Virdis from Rutgers University; Jessica Wilks, Melissa Kane, Helen Beilinson, Stanislav Dikiy, Laure Case, Michele Witkowski and Alexander Chervonsky from the University of Chicago; and Derry Roopenian from the Jackson Laboratory, Maine.

Tagged: Biological Sciences, Genetics, immune system, immunology, Microbiology, retroviruses, Tatyana Golovkina, viruses

First winged mammals from the Jurassic period discovered

Wed, 08/09/2017 - 12:00
 A mother with a baby in suspending roosting posture, climbing on tree trunk, and in gliding (Reconstruction by April I. Neander/UChicago).

Maiopatagium in Jurassic forest in crepuscular (dawn and dusk) light: A mother with a baby in suspending roosting posture, climbing on tree trunk, and in gliding (Reconstruction by April I. Neander/UChicago).

Two 160 million-year-old mammal fossils discovered in China show that the forerunners of mammals in the Jurassic Period evolved to glide and live in trees. With long limbs, long hand and foot fingers, and wing-like membranes for tree-to-tree gliding, Maiopatagium furculiferum and Vilevolodon diplomylos are the oldest known gliders in the long history of early mammals.

The new discoveries suggest that the volant, or flying, way of life evolved among mammalian ancestors 100 million years earlier than the first modern mammal fliers. The fossils are described in two papers published this week in Nature by an international team of scientists from the University of Chicago and Beijing Museum of Natural History.

“These Jurassic mammals are truly ‘the first in glide,’” said Zhe-Xi Luo, PhD, professor of organismal biology and anatomy at the University of Chicago and an author on both papers. “In a way, they got the first wings among all mammals.”

“With every new mammal fossil from the Age of Dinosaurs, we continue to be surprised by how diverse mammalian forerunners were in both feeding and locomotor adaptations. The groundwork for mammals’ successful diversification today appears to have been laid long ago,” he said.

Adaptations in anatomy, lifestyle and diet

The ability to glide in the air is one of the many remarkable adaptations in mammals. Most mammals live on land, but volant mammals, including flying squirrels and bats that flap bird-like wings, made an important transition between land and aerial habitats. The ability to glide between trees allowed the ancient animals to find food that was inaccessible to other land animals. That evolutionary advantage can still be seen among today’s mammals such as flying squirrels in North America and Asia, scaly-tailed gliders of Africa, marsupial sugar gliders of Australia and colugos of Southeast Asia.

The Jurassic Maiopatagium and Vilevolodon are stem mammaliaforms, long-extinct relatives of living mammals. They are haramiyidans, an entirely extinct branch on the mammalian evolutionary tree, but are considered to be among forerunners to modern mammals. Both fossils show the exquisitely fossilized, wing-like skin membranes between their front and back limbs. They also show many skeletal features in their shoulder joints and forelimbs that gave the ancient animals the agility to be capable gliders. Evolutionarily, the two fossils, discovered in the Tiaojishan Formation northeast of Beijing, China, represent the earliest examples of gliding behavior among extinct mammal ancestors.

Click to view slideshow.

The two newly discovered creatures also share similar ecology with modern gliders, with some significant differences. Today, the hallmark of most mammal gliders is their herbivorous diet that typically consists of seeds, fruits and other soft parts of flowering plants.

But Maiopatagium and Vilevolodon lived in a Jurassic world where the plant life was dominated by ferns and gymnosperm plants like cycads, gingkoes and conifers – long before flowering plants came to dominate in the Cretaceous Period, and their way of life was also associated with feeding on these entirely different plants. This distinct diet and lifestyle evolved again some 100 million years later among modern mammals, in examples of convergent evolution and ecology.

“It’s amazing that the aerial adaptions occurred so early in the history of mammals,” said study co-author David Grossnickle, a graduate student at the University of Chicago. “Not only did these fossils show exquisite fossilization of gliding membranes, their limb, hand and foot proportion also suggests a new gliding locomotion and behavior.”

Thriving among dinosaurs

A gliding mammaliaform feeding on the soft parts of a bennethelian plant of the Jurassic. (Illustration by April I. Neander/UChicago)

Early mammals were once thought to have differences in anatomy from each other, with limited opportunities to inhabit different environments. The new glider fossils from the dinosaur-dominated Jurassic Period, along with numerous other fossils described by Luo and colleagues in the last 10 years, however, provide strong evidence that ancestral mammals adapted to their wide-ranging environments despite competition from dinosaurs.

“Mammals are more diverse in lifestyles than other modern land vertebrates, but we wanted to find out whether early forerunners to mammals had diversified in the same way,” Luo said. “These new fossil gliders are the first winged mammals, and they demonstrate that early mammals did indeed have a wide range of ecological diversity, which means dinosaurs likely did not dominate the Mesozoic landscape as much as previously thought.”

The study “New Gliding Mammaliaforms from the Jurassic” was supported by the Beijing Science and Technology Commission and the University of Chicago. Additional authors include Qing-Jin Meng, Qiang Ji, Di Liu, Yu-Guang Zhang and April I. Neander.

The study “New Evidence for Mammaliaform Ear Evolution and Feeding Adaptation in a Jurassic Ecosystem,” was supported by the Beijing Science and Technology Commission, and the University of Chicago. Additional authors include Qing-Jin Meng, Qiang Ji, Yu-Guang Zhang, Di Liu and April Neander.

Tagged: Biological Sciences, China, David Grossnickle, dinosaurs, fossils, Jurassic Period, paleontology, Zhe-Xi Luo
Flying mammal fossil reconstruction

Big data yields surprising connections between diseases

Mon, 08/07/2017 - 10:00
Andrey Rzhetsky

Andrey Rzhetsky, PhD, the Edna K. Papazian Professor of Medicine and Human Genetics

Using health insurance claims data from more than 480,000 people in nearly 130,000 families, researchers at the University of Chicago have created a new classification of common diseases based on how often they occur among genetically-related individuals.

Researchers hope the work, published this week in Nature Genetics, will help physicians make better diagnoses and treat root causes instead of symptoms.

“Understanding genetic similarities between diseases may mean that drugs that are effective for one disease may be effective for another one,” said Andrey Rzhetsky, PhD, the Edna K. Papazian Professor of Medicine and Human Genetics at UChicago who was the paper’s senior author. “And for those diseases with a large environmental component, that means we can perhaps prevent them by changing the environment.”

The results of the study suggest that standard disease classifications–called nosologies–based on symptoms or anatomy may miss connections between diseases with the same underlying causes. For example, the new study showed that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome, an inflammatory disorder of the intestine.

Rzhetsky and a team of researchers analyzed records from Truven MarketScan, a database of de-identified patient data from more than 40 million families in the United States. They selected a subset of records based on how long parents and their children were covered under the same insurance plan within a time frame most likely to capture when children were living in the same home with their parents. They used this massive data set to estimate genetic and environmental correlations between diseases.

Next, using statistical methods developed to create evolutionary trees of organisms, the team created a disease classification based on two measures. One focused on shared genetic correlations of diseases, or how often diseases occurred among genetically-related individuals, such as parents and children. The other focused on the familial environment, or how often diseases occurred among those sharing a home but who had no or partially matching genetic backgrounds, such as spouses and siblings.


New disease classifications created by analyzing genetic and environmental correlations among family members

The results focused on 29 diseases that were well represented in both children and parents to build new classification trees. Each “branch” of the tree is built with pairs of diseases that are highly correlated with each other, meaning they occur frequently together, either between parents and children sharing the same genes, or family members sharing the same living environment.

“The large number of families in this study allowed us to obtain precise estimates of genetic and environmental correlations, representing the common causes of multiple different diseases,” said Kanix Wang, a graduate student at UChicago and lead author of the study. “Using these shared genetic and environmental causes, we created a new system to classify diseases based on their intrinsic biology.”

Genetic similarities between diseases tended to be stronger than their corresponding environmental correlations. For the majority of neuropsychiatric diseases, such as schizophrenia, bipolar disorder and substance abuse, however, environmental correlations are nearly as strong as genetic ones. This suggests there are elements of the shared, family environment that could be changed to help prevent these disorders.

Rzhetsky ICD-9 phenotypic

Two traditional disease classifications, ICD-9 (left) and a phenotypic model (right) based on symptoms

The researchers also compared their results to the widely used International Classification of Diseases Version 9 (ICD-9) and found additional, unexpected groupings of diseases. For example, type 1 diabetes, an autoimmune endocrine disease, has a high genetic correlation with hypertension, a disease of the circulatory system. The researchers also saw high genetic correlations across common, apparently dissimilar diseases such as asthma, allergic rhinitis, osteoarthritis and dermatitis.

The study, “Classification of common human diseases derived from shared genetic and environmental determinants” was supported by the Defense Advanced Research Projects Agency (DARPA) Big Mechanism program, the National Institutes of Health, and a gift from Liz and Kent Dauten. Additional authors include Hallie Gaitsch from the University of Chicago, Hoifung Poon from Microsoft Research, and Nancy J. Cox from Vanderbilt University.

Tagged: Andrey Rzhetsky, big data, bioinformatics, Biological Sciences, biostatistics, disease classification, Genetics, nosology

Gene therapy via skin could treat many diseases, even obesity

Thu, 08/03/2017 - 11:00


A research team based at the University of Chicago has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In the August 3, 2017 issue of the journal Cell Stem Cell, the researchers provide “proof-of-concept.” They describe gene-therapy administered through skin transplants to treat two related and extremely common human ailments: type-2 diabetes and obesity.

Xiaoyang Wu, PhD

Xiaoyang Wu, PhD

“We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems,” said study author Xiaoyang Wu, PhD, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. “We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin.”

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patient’s wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

“The mouse system is less mature,” Wu said. “It took us a few years to optimize our 3D skin organoid culture system.”

This study, “Engineered epidermal progenitor cells can correct diet-induced obesity and diabetes,” is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. “We have a better than 80 percent success rate with skin transplantation,” Wu said. “This is exciting for us.”

Using CRISPR and skin grafts, researchers boost insulin levels to reduce weight

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormone’s half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

wu skin graft

Immunofluorescence imaging shows normal skin differentiation and tissue architecture of transplanted skin grafts

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, “skin-like organoid.” Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

“Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies,” the authors wrote.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that “cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.”

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide “significant benefits for the treatment of many human diseases,” the authors note.

“We think this can provide a long-term safe option for the treatment of many diseases,” Wu said. “It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.”

wu mice

When normal and gene-altered mice ate the high-fat diet—along with varying levels of doxycycline to induce GLP1 release—mice expressing GLP1 (left) gained less weight gain while normal mice (right) grew fat

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.

There is also a need. More than 100 million U.S. adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than 2 out of 3 adults are overweight. More than 1 out of 3 are considered obese.

Additional authors of the study were Japing Yue, Queen Gou, and Cynthia Li from the University of Chicago and Barton Wicksteed from the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society and the V Foundation funded the study.

Tagged: Biological Sciences, CRISPR, Diabetes, Genetics, immune system, immunology, Obesity, skin grafts, skin transplantation, Xiaoyang Wu