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.
“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
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
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
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.
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.
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
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.
“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.
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.”
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
A new mathematical model of ecology created by University of Chicago scientists provides the most accurate reproduction to date of natural biodiversity, according to a new paper in the journal Nature.
For almost a century, ecologists have conceptualized an ecosystem as the sum of pairwise interactions, such as predator and prey, herbivore and plant, or parasite and host. However, equations based on that theory failed to replicate the diversity and resilience of natural ecosystems.
Building upon previous work that modeled competition between species as similar to a game of rock/paper/scissors, a team led by Stefano Allesina, Professor of Ecology & Evolution at the University of Chicago, found that adding additional competitors could generate stable and robust model ecosystems.
“Ecologists feel more comfortable with pairs, but that doesn’t mean that nature operates in pairs,” said Allesina, who is also a Computation Institute fellow and faculty. “No one had proposed equations for triplets or quadruplets. We wanted to test if these relationships really make a difference, and the answer is a resounding yes; they make a huge difference.”
Ecologists have long debated the existence and importance of higher-order interactions, where the relationship of two species can be influenced by a third. For example, the trio of a carnivore, a herbivore, and a plant would be treated as independent carnivore-herbivore and herbivore-plant pairs. But the presence of a carnivore could force the herbivore into hiding, affecting its consumption of the plant — a higher-order interaction that disrupts the pairwise model.
“If you measure these pairs and put them together, they don’t explain the system,” Allesina said. “Basically the presence of the predator modifies the relationship between the plant and the herbivore. Something emerges that cannot be explained by pairs.”
In the Nature paper, Allesina, postdoctoral researchers Jacopo Grilli and György Barabás, and graduate student Matthew Michalska-Smith considered a simple scenario. In a hypothetical forest where every so often one tree dies and leaves a hole in the canopy, who will win a battle of species to fill that ecological gap?
If a pair of species compete for each opening, the dominant competitor will eventually drive the other extinct and lower ecosystem diversity, unless they are perfectly equal. In the “rock paper scissors” model proposed by Allesina’s group in 2011, overlapping dominance (e.g. rock beats scissors but loses to paper) of multiple species can maintain a rich ecosystem, but the biodiversity cycles between high and low in a pattern not observed in nature.
To instead model the system with higher-order interactions, the team simulated competition using a “stepladder tournament” format similar to that used in televised bowling events. Here, the winner of a two-way match goes on to play against a third competitor, and the winner of that match plays a fourth, and so on, for any number of competitors. With an equation that aggregates all possible outcomes of one of these “chain of competitions,” the researchers found they could produce a system with high and stable biodiversity, similar to observations from the real world.
Unlike other ecological models, their equation produced realistic results under a wide range of starting conditions, as well as in both a closed system — akin to bacteria competing in a laboratory dish — and an open system, where new species enter and leave the ecosystem over time.
“When there is even the probability of just three species interacting, it completely changes the dynamics,” Grilli said. “As long as there is a very small probability for higher-order interactions to happen, then there are going to be huge changes. It’s really an effect that is super robust.”
The researchers now hope to test their new equation in laboratory experiments, observing whether actual competition between bacterial species follows their model’s predictions. In the meantime, by mathematically proving the strong influence of these higher-order interactions, Allesina expects the model to further push theoretical ecology into new territory.
“I think that this opens the door for a number of models that people had not considered before, that are maybe even simpler than this one,” Allesina said. “It is very rare in ecology to see a model that has this kind of global stability, such that wherever you start you end up in the same point.”
The new model also led Allesina’s group back to familiar territory: the world of competitive rock paper scissors.
“If you apply this equation to come up with rules to play rock paper scissors with three people, these turn out to be the official rules that they use,” Grilli said. “In fact, we have a way to generalize for any number of players, so if you want to play the game with 8 people, we can do that.”
Tagged: biodiversity, Biological Sciences, computational biology, ecology, ecology and evolution, Evolution, George Barabas, Jacopo Grilli, Matthew Michalska-Smith, stefano allesina
Twenty-four University of Chicago faculty members have received named professorships or were appointed distinguished service professors, including seven from UChicago Medicine and the Biological Sciences Division.
Zeresenay “Zeray” Alemseged has been named the Donald N. Pritzker Professor in Organismal Biology and Anatomy and the College.
A noted paleoanthropologist, Alemseged studies the origin of early human ancestors and the environmental factors that influenced their evolution. He established and led the Dikika Research Project, in which Alemseged made several breakthrough findings, including the discovery of the almost-complete fossilized remains of “Selam,” a 3.3-million-year-old child of the species Australopithecus afarensis. Now known as “the world’s oldest child,” it is the most complete skeleton of a human ancestor discovered to date and represents a major advancement in the understanding of human and pre-human evolution.
Alemseged is a fellow of the American Association for the Advancement of Science, and the co-founder and president of the East African Association of Paleontologists and Paleoanthropologists. He was a senior scientist at the Max Planck Institute and recently the Irvine Chair and senior curator of anthropology at the California Academy of Sciences.
Joy Bergelson has been named the James D. Watson Professor in Ecology and Evolution and the College.
Bergelson’s work focuses on the plant Arabidopsis thaliana and the community of bacteria that inhabit it, with particular interest in understanding how the ecology of these interactions shapes evolutionary change. Her studies combine molecular evolutionary research with functional genomics under natural field conditions to test models of host-pathogen co-evolution. Along with colleagues she also has pioneered the development of Arabidopsis thaliana as a system for genome-wide mapping studies, which culminated in the Arabidopsis 1001 project. She received the 2017 BSD Distinguished Investigator award for this body of work.
The chair of the Department of Ecology and Evolution, Bergelson is a member of three UChicago committees, and has served on dozens of other departmental, divisional and university committees, National Science Foundation and U.S. Department of Agriculture panels, international advisory boards and journal editorial boards. She is a fellow of the American Association for the Advancement of Science and has served as chair of the AAAS Biology section.
John M. Cunningham has been named the George M. Eisenberg Professor in Pediatrics and the College.
Cunningham is an internationally known expert in the treatment and research of childhood cancers and blood diseases. He has particular expertise in treating leukemia, immunodeficiencies, sickle cell disease and thalassemia. He is a recognized leader in the field of pediatric stem cell transplantation and has developed novel uses for this life-saving treatment. Cunningham studies the transcriptional mechanisms operative in hematopoiesis and leukemia, and the development of clinical trials for the treatment of leukemia and genetic diseases.
Cunningham’s research has received support from the National Heart, Lung, and Blood Institute; the American Society of Hematology; and other prominent scientific organizations. He is a member of the scientific council of the American Cancer Society and a member of the editorial board of The Oncologist.
Thomas F. Gajewski has been named the first AbbVie Foundation Professor of Cancer Immunotherapy in Pathology.
Gajewski’s team members study ways to overcome a tumor’s ability to elude the immune system, with a focus on drugs that help the immune system, especially T cells, gain access to tumor sites. They have discovered genetic clues that correlate with response versus resistance, enabling them to identify new therapies to overcome resistance and expand efficacy. They also discovered that certain components of the gut microbiota—microbes that live in a patient’s digestive tract—could stimulate the immune system to attack tumor cells. They are now refining this approach and analyzing a large cohort of human samples.
Earlier this year, Gajewski received an outstanding investigator award from the National Institutes of Health for productivity in cancer research. Gajewski is an editor for Cancer Research and the Journal for Immunotherapy of Cancer and past president of the Society for Immunotherapy of Cancer.
Rex Haydon has been named the Simon and Kalt Families Professor in Orthopaedic Surgery.
An orthopedic surgeon and physician-scientist, Haydon specializes in the comprehensive treatment of tumors in bone or soft tissue. He works closely with patients hoping to avoid limb amputation as well as those who need reconstructive surgery on their upper and lower extremities. Haydon’s research focuses on advancing the treatment of musculoskeletal tumors. He’s the author of more than 120 articles and book chapters and has accepted career development awards from both the Orthopaedic Research and Education Foundation and the National Institutes of Health.
Beyond his work in the University of Chicago’s Department of Orthopaedic Surgery and Rehabilitation Medicine, Haydon is also the associate director of the University of Chicago Medicine Molecular Oncology Laboratory.
Sonali M. Smith has been selected as the first Elwood V. Jensen Professor in Medicine.
The director of the lymphoma program, Smith is an expert on lymphoma treatment and has made outstanding contributions to the field through clinical care, education and clinical research. She studies new agents and combinations in the management of both treatment-naïve and relapsed/refractory lymphomas. She is currently studying the role of stem cell transplantation for patients with high-risk follicular lymphoma.
Smith is vice chair of the Southwest Oncology Group Lymphoma Committee, where she oversees clinical trial development and mentors faculty. She chairs the American Society of Oncology’s Women in Oncology Subcommittee and is the incoming chair of ASCO’s Continuous Professional Development Committee. She is co-editor of ASCO’s Hematology and co-chair of the Center for International Blood and Marrow Transplant Research Lymphoma Working Group. Smith serves on the editorial board of the Journal of Clinical Oncology and Cancer. She is an elected fellow of Pritzker’s Academy of Distinguished Medical Educators and a senior faculty scholar in the Bucksbaum Institute. She has more than 140 publications and lectures extensively to peers and patients nationally and internationally.
Nir Uriel has been named the Louis Block Professor in Medicine.
Uriel, who is director of the Heart Failure, Transplant and Mechanical Circulatory Support program, is a leader in the field of heart failure, mechanical circulatory support and heart transplantation. He specializes in caring for patients who require mechanical circulatory support, including ventricular assist devices. Uriel’s research focuses on advanced heart failure physiology, heart transplant and mechanical circulatory support. Uriel specialized and reported physiological changes and developed treatment algorithms for patients supported with Mechanical Circulatory Support that are being used worldwide. These findings were published in the Journal of American College of Cardiology.
Uriel has a strong interest in high-risk transplant populations, including HIV-positive patients and patients who have received mediastinal radiation due to tumors or prior transplants. He has improved treatment protocols and patient care for these high-risk groups.
Tagged: Biological Sciences, Cancer, ecology and evolution, Haydon, Heart & Vascular, John Cunningham, Joy Bergelson, Nir Uriel, Orthopedics, paleontology, Pediatrics, Sonali Smith, Thomas Gajewski, Transplant, Zeray Alemseged
Pregnancy presents a conundrum for the immune system. It’s built to fight off any invaders with foreign DNA, from viruses and bacteria to, unfortunately, lifesaving transplanted organs. Since a fetus has DNA from both parents, the mother’s immune system needs to have a way to remain tolerant of the father’s foreign genes and give them a pass.
One way the immune system acknowledges the special circumstances of pregnancy is with proteins produced by genes in the major histocompatibility complex (MHC), which help the immune system identify foreign bodies. In most situations, MHC proteins on healthy cells present little pieces of proteins called peptides, which are like badges to show to the body’s security guards, roaming immune T cells. If they see a human or “self” peptide, everything checks out; but if they see a peptide from a virus or foreign tissue, the guards sound the alarm and trigger an immune response to kill the cell.
But during pregnancy, the fetus doesn’t express a lot of these classical MHC proteins that are recognized by T cells responding to specific peptides, perhaps as a way to avoid rejection. Instead, fetal and uterine cells express related, but slightly different, non-classical MHC proteins that regulate maternal NK (natural killer) cells that supervise the extensive changes that occur in the uterus during pregnancy.
Charles Dulberger is a PhD candidate in the department of Biochemistry and Molecular Biophysics at the University of Chicago (and Science Life contributor) who studies the three-dimensional structures of proteins that control immune responses. The shape and surface topology of proteins is important to how they function. They have unique notches and grooves that allow them to interact with other proteins or bind molecules with matching shapes, like puzzle pieces fitting together.
In a paper published last month in the journal Immunity, Dulberger led a team that described the structure of HLA-F, one of the specialized MHC proteins involved in pregnancy, for the first time. It hasn’t been studied as thoroughly as some of its neighbors, and while it turns out that it functions in many of the same ways, it has some interesting differences that may be tied to the evolution of pregnancy in humans.
Scientists haven’t been sure how HLA-F is involved in the immune system, or whether it presents peptides in the same way as other MHC proteins. Using x-ray crystallography and other biochemical methods to define its structure, Dulberger and his colleagues were able to confirm that HLA-F does bind peptides, which means it could be recognized by T cell receptors too.
“Now that we know that HLA-F can present peptides, we want to know if T cells and NK cells can use their receptors to perceive these peptides as a signal to respond to,” he said. “If T cell receptors do recognize them, that opens the door for potential therapeutics that exploit or modify this interaction, because T cells are important in a lot of diseases, including many cancers.”
Most MHC molecules have a well-defined, linear groove shaped to hold peptides, like a Lego piece that snaps perfectly into place. But HLA-F has a slightly different groove that is partially blocked off, so part of the peptide protrudes out of the groove. What’s interesting is that these changes are only present in human and orangutan HLA-F, who notably both have nine month pregnancies—they’re not there in HLA-F for chimpanzees, which have a shorter eight-month gestation.
Dulberger said that the differences may contribute to how the mother’s immune system tolerates a longer pregnancy. The structure and function of HLA-F is important to understanding aspects of pregnancy, he said, but learning more about its specific shape (and of others like it) will also help us understand diseases that manipulate the immune system, like cancer.
“We can learn a lot about how cells communicate by understanding the structure of proteins and protein complexes because proteins are kind of like the eyes, ears and mouth of the cell,” Dulberger said. “They sense their environment and signal to each other via protein-protein interactions.”
Understanding protein structure is also really important for the development of new medicines because most drugs used in the clinic target specific proteins.
“Once you understand the molecular architecture of a protein receptor and how it binds another protein, you can design drugs that interfere with that interaction or modify it in an advantageous manner,” he said. “So, you can imagine if you had a cancer that expresses HLA-F at a really high level to inhibit the immune system, you can develop an antibody or small molecule inhibitor to block that, and then the immune cells will be able to fight the cancer cells again.”
Tagged: Biological Sciences, Charles Dulberger, Genetics, immune system, molecular biology, pregnancy, protein structure
A study by researchers at the University of Chicago Medicine shows that when mice that are genetically susceptible to developing inflammatory bowel disease (IBD) were given antibiotics during late pregnancy and the early nursing period, their offspring were more likely to develop an inflammatory condition of the colon that resembles human IBD.
The antibiotic treatment also caused lasting changes in the gut microbiome of mothers that were passed on to their offspring. While their offspring developed disease, adult mice given antibiotics did not see an increase in IBD. This suggests that the timing of antibiotic exposure is crucial, especially during the early developmental period after birth when the immune system is undergoing maturation.
“The newborn mice inherited a very altered, skewed population of microbes,” said Eugene B. Chang, MD, Martin Boyer Professor of Medicine at the University of Chicago, Director of the Microbiome Medicine Program of the Microbiome Center, and senior author of the study, published this week in the journal Cell Reports. “None of the mothers developed IBD, but even though they had the same genetic background, the offspring with an altered microbiome during this critical period of immune development became highly susceptible to the development of colitis.”
Chang cautioned, however, that these results from an animal study should not be taken as a reason for pregnant women or those nursing newborn infants to avoid antibiotics when they are needed to treat dangerous bacterial infections. Instead, he said, it should serve as a reminder that best practices dictate avoiding casual, indiscriminant over usage ‘just to be safe’, say, for a common cold that is most likely caused by a virus.
“Antibiotics should absolutely be used judiciously when they’re indicated,” Chang said. “But we as physicians should keep in mind the importance of antimicrobial stewardship, because this study suggests that it may have long term consequences that potentially impact health and risk for certain diseases.”
Lasting changes in the gut microbiome
Several epidemiological studies have suggested that exposure to antibiotics during the peripartum period (late pregnancy and the nursing period after birth) increases the risk for IBD in humans. Direct evidence for this association has been lacking, however, because of vast differences in individual gut microbiomes, challenges in controlling for variables, and the limits of conducting clinical experiments in pregnant women and infants.
To address these issues, Jun Miyoshi, MD, PhD, a postdoctoral scholar, and Alexandria Bobe, a graduate student in Chang’s lab, designed a series of experiments with a standard genetic mouse model for IBD to study the timing of antibiotic treatment during the peripartum period and its impact on gut microbes and immune system development in offspring. The researchers gave cefoperazone, a commonly-used antibiotic, to mouse mothers in the late stages of pregnancy through the period that they nursed their pups, i.e. to mimic a common clinical scenario of early antibiotic exposure in humans. None of the adult mice treated with antibiotics developed colitis, but their pups exhibited a high risk for developing colitis compared to those from mothers that were not treated with antibiotics.
Using state-of-the-art, high-throughput sequencing technologies, the team also analyzed the gut microbial population structures of mothers and their offspring. The mothers showed a decrease in diversity of bacteria, and changes in the relative numbers of certain groups of bacteria. For example, there were fewer populations of Bacteroidetes and more from the phyla Firmicutes and Verrucomicrobia. Surprisingly, these changes persisted even four to eight weeks after stopping the antibiotic treatment.
The mouse pups also had similar changes in their gut bacteria, with microbial communities matching their mothers at birth. The diversity of microbes in these pups was significantly different from that of mice not treated with antibiotics, and these differences lasted into adulthood.
“What this should tell us is, at least as physicians, is that antibiotics are not as innocuous as we think they are, and injudicious, casual use of them can have consequences,” Chang said. “When they’re used during pregnancy or early childhood, they can disturb the development of a normal gut microbiome which would otherwise be essential for proper immune development. In genetically susceptible hosts, the inability to develop the immune system properly can have negative consequences like inflammatory bowel disease or any other kinds of complex immune disorders.”
Working toward a definition of health
Chang said that understanding more about the microbiome in an unhealthy state can help scientists begin to learn how to promote the development of a microbiome that sets the stage for a healthy immune system.
“What this study showed is what an ‘unhealthy’ microbiome looks like, so presumably whatever is missing may be important to promote health,” he said. “What we want to eventually develop is a microbial cocktail we can give to infants that ensures that they develop properly, metabolically and immunologically. That’s going to have a significant impact on human health, by reducing risk for many types of diseases and by promoting wellness.”
The study, “Peripartum Exposure to Antibiotics Promotes Persistent Gut Dysbiosis, Immune Imbalance, and Colitis in Genetically Prone Offspring,” was supported by the NIDDK Digestive Disease Core Research Center, the Microbiome Medicine Program of the Microbiome Center at the University of Chicago, the Peter and Carol Goldman Family Research Fund, and the GI Research Foundation of Chicago. Additional authors include, Sawako Miyoshi, Yong Huang, Nathaniel Hubert, Tom O. Delmont, A. Murat Eren and Vanessa Leone from the University of Chicago.
Tagged: antibiotics, Biological Sciences, Eugene Chang, Gastroenterology, IBD, inflammatory bowel disease, microbiome, Microbiome Center, pregnancy, ulcerative colitis
To understand how the human genome governs what a cell does and how it looks, it’s important for scientists to understand what parts of the genome are activated in different cell types, and how these parts act together to make sure the cell functions properly. To study these questions, researchers have developed tools that measure the structure and activity of genetic material in cells.
In living cells the genome is tightly packaged in a structure called chromatin. Chromatin consists of the genomic DNA itself, proteins, and RNA. When the cell is actively transcribing and replicating DNA, the chromatin is more loosely packed or accessible. Scientists can measure chromatin accessibility to tell which regions of the genome are probably active at a given time. They can also measure levels of DNA methylation, when molecules are added to DNA to “turn off” parts of the genome, to see which regions of DNA might be repressed.
Sebastian Pott, a research assistant professor in the Department of Human Genetics at the University of Chicago, is working to answer some of these questions. In a new study published in the journal eLife, he tested a tool that measures both chromatin accessibility and DNA methylation to see if it could be applied to single cells. Science Life spoke to him about the work.
Why was it important to see if this method works for single cells?
Until recently, most of these studies were performed using large samples that contained thousands of cells. This is beneficial because the starting material is not limited. However, it has become clear that even cells that are seemingly of the same type differ in subtle but important ways. These differences are lost when using bulk samples, which are more likely to reflect the average of a cell population.
It is therefore necessary to develop methods that measure these features in single cells. Because the amount of starting material [from a single cell] is very small, it is critical to modify many of the established techniques when adapting them for single cell measurements. Studying features of the genome in single cells has the added limitation that the sample cannot be divided up for multiple assays. To address these limitations, this study was designed to test whether a method that measures both chromatin accessibility and DNA methylation, called NOMe-seq, could be applied to single cells. It builds on previous work by the labs of Peter Jones [from the Van Andel Research Institute] and Michael Kladde [from the University of Florida]. In this study, I tested whether this protocol could be modified and applied to single cells; the modified protocol was named “single cell NOMe-seq,” or scNOMe-seq.
Did it work?
This study provides evidence that scNOMe-seq detects endogenous DNA methylation and chromatin accessibility at the same time from a single cell. To test the performance of scNOMe-seq the study was performed in well-characterized human cell lines. Regulatory regions (e.g. promoters of active genes or active regulatory regions and enhancers) showed characteristic chromatin accessibility in single cells. As previously documented in bulk samples, DNA methylation in these regions was inversely correlated with chromatin accessibility. This proof-of-principle study therefore established that scNOMe-seq recovers the same features of chromatin organization observed in bulk samples.
What will scientists be able to do with a tool like this?
Many biological samples contain mixtures of cell types. As a result, it is often difficult when studying such a sample to extract a specific cell type for detailed characterization. For example, not all cell types in a tissue might be known in advance or have specific markers that would allow one to label them and separate them from the rest. In such cases, scNOMe-seq can be applied to measure regulatory activity (i.e. DNA methylation and chromatin accessibility) in individual cells without first isolating specific cell types. The resulting single cell data could then be used to classify and identify distinct cell types or states. This approach could be particularly useful when studying tumor samples which are often very heterogeneous.
What was your biggest challenge during this study?
Cells contain extremely small amounts of DNA and the biggest challenge of this work was to capture as much of the DNA in a cell to be able to measure anything at all. Only after very long process it is possible to assess whether this method works, and so it was pretty cool to see that this approach actually turned out data that were very similar to data produced from thousands of cells.
What are you working on next?
The aim of this study was to provide proof-of-principle that this method reliably obtains data from single cells. But of course, the motivation to develop the method was to use it to study biologically and clinically significant problems. For example, I am planning to apply this technique to study the activation of immune cells. I am particularly interested in understanding how responses of immune cells are regulated in individual cells and what might be different in cells of individuals with allergies.
Tagged: Biological Sciences, chromatin, DNA, DNA methylation, genes, Genetics, genome, human genetics, human genome research, Sebastian Pott
Neuroscientists from the University of Chicago argue that research on how memories form in the brain should consider activity of groups of brain cells working together, not just the connections between them.
Memories are stored as “engrams,” or enduring physical or chemical changes to populations of neurons that are triggered by new information and experiences. Traditional thinking about how these engrams form centers on the ability of connections between neurons to strengthen or weaken over time based on what information they receive, or what’s known as “synaptic plasticity.” The new proposal, published this week in the journal Neuron, argues that while synaptic plasticity establishes the map of connectivity between individual neurons in an engram, it is not enough to account for all aspects of learning. A second process called “intrinsic plasticity,” or changes in the intensity of activity of neurons within an engram, plays an important role as well.
“Synaptic plasticity does not fully account for the complexity of learning mechanisms that we are aware of right now,” said Christian Hansel, PhD, professor of neurobiology and senior author of the new paper. “There were elements missing, and with the introduction of intrinsic plasticity, all of a sudden you see a system that is more dynamic than we thought.”Viewing activity of the brain as a whole
In recent studies using optogenetic tools, which enable scientists to control the activity of neurons with light, researchers have been able to monitor memory storage and retrieval from brain cells. Optogenetic tools give scientists a window to the activity of the brain as a whole, even in living animals. These new studies show how both individual neurons and groups, or ensembles, of neurons work together while memory and learning processes take place—often without requiring any changes to the connections between synapses.
For instance, synaptic plasticity relies on repeated conditioning to develop stronger connections between cells, meaning that an animal has to experience something several times to learn and form a memory. But, of course, we also learn from single, brief experiences that don’t necessarily trigger changes in the synapses, meaning that another, faster learning process takes place.
The authors point to several studies showing that intrinsic plasticity is a nearly instantaneous mechanism that likely has a lower threshold, or takes fewer experiences, to initiate. Thus, it might be more appropriate for fast learning resulting from single experiences, instead of the slow, adaptive process involved with synaptic plasticity.
Theories about memory formation also don’t account for the relative strength of activity in neurons once connections between them have been established, the authors write. If you think of how memories are stored as working like the lights in a room, synaptic connections are the electrical wiring that determine how the lights are connected and what input (electricity) they receive. Changing how the lights are wired (i.e. the synaptic plasticity) obviously affects how they function, but so do the switches and light bulbs. Intrinsic plasticity is the ability to manipulate the intensity of the light without changing the wiring, like using dimmer switches or three-way bulbs. Both kinds of changes have an effect independently, but they work together to light the room.
“They are two ideas that are very important to learning and memory and we bring them together in this paper,” said postdoctoral scholar Heather Titley, PhD, first author of the paper. “They’re not mutually exclusive.”
The authors emphasize that this new line of thinking is just a starting point. More experiments should be designed, for instance, to tease out the relative effects of synaptic versus intrinsic plasticity on learning and memory. But given the evidence produced by new technology, they argue that it’s time to expand our thinking about how memories form.
“People might argue whether this intrinsic plasticity is really something that plays a major role or not,” said Nicolas Brunel, PhD, professor of neurobiology and statistics, and another author of the paper. “But I don’t think people can argue that it doesn’t play any role, because there is an increasing amount of evidence that it does.”
Tagged: Biological Sciences, Brain, Christian Hansel, Heather Titley, memories, memory, neurobiology, Neuroscience, Nicholas Brunel
A list of professors’ last names can reveal, measure unethical hiring
Using lists of names collected from publicly available websites, two University of Chicago researchers have revealed distinctive patterns in higher education systems, ranging from ethnic representation and gender imbalance in the sciences, to the presence of academic couples, and even the illegal hiring of relatives in Italian universities.
“This study was an exercise in exploiting bare-bones techniques,” said author Stefano Allesina, PhD, professor of ecology & evolution and a member of the Computation Institute at the University of Chicago. “We wanted to analyze the simplest form of data you could imagine: lists of names. That’s all we had. We wondered what kinds of information we could extract from such a meager source of data. We also asked: how could we use this to explore real-world problems?”
For the study — “Last name analysis of mobility, gender imbalance, and nepotism across academic systems,” published July 3, 2017 in the Proceedings of the National Academy of Sciences — Allesina and postdoctoral scholar Jacopo Grilli, PhD, acquired lists of the surnames of all Italian academics in the four years 2000, 2005, 2010 and 2015. For comparison, they also gathered lists of all researchers currently working at the Centre National de la Reserche Scientifique (CNRS) in France, and those working at research-intensive public institutions in the United States.
Then they counted the number of professors in each department who shared last names and contrasted that to the number expected by chance. They found three possible explanations for an overabundance of identical last names. An unusually high proportion of name sharing could be due to geography; certain names are typical of a region. Or, immigration could have an impact, for example, the influx of Asian faculty to the United States in disciplines such as in mathematics and computer science.
If the clustering of names cannot be explained by these two factors — which was the case in certain disciplines and regions in Italy — then the data point to nepotistic hires: professors who recruit their relatives for academic positions.
The Allesina laboratory is not new to this type of analysis. In a 2011 paper published in PLoS One, Allesina demonstrated that certain disciplines (law, medicine, engineering) in Italian universities displayed a severe scarcity of last names, raising the suspicion of nepotism.
That study caused “quite a stir in Italy,” Allesina said. The publication followed a complete overhaul of the nation’s academic system. The reform, passed in late 2010, included a provision intended to prevent professors from recruiting relatives by shifting hiring and funding decisions away from the universities to independent panels. The perception at the time was that “promotions and funding were often awarded on the basis of connections rather than merit, providing mediocre and unproductive professors with jobs for life while pushing many of the country’s brightest minds abroad,” Allesina said.
Grilli and Allesina decided to take a closer look at the law’s impact since 2010 and to compare the prevalence of nepotism in Italy with other countries. They found that nepotism in Italy appears to have declined somewhat over the period from 2000 to 2015. In 2000, seven of the 14 fields measured showed clear signs of nepotism. That fell to five fields in 2010, and only two, chemistry and medicine, by 2015.
The 2010 law, they point out, was not the only factor in the decrease of apparent nepotism. Much of the decline, the researchers point out, could be traced to an increase in faculty retirements and a dearth of new hires.
The Italian university system has been “virtually butchered over the last decade,” Allesina said, with a staggering 10 percent overall loss of faculty, and losses of 20 to 30 percent of the faculty at several leading universities. “This had a strong effect on new hires,” he said, “but only a limited impact on favoritism over the whole university system.”
The researchers’ focus on last names illuminates some recent changes in U.S. academics as well. When faculty last names were randomized by field, the huge impact of immigration on U.S. universities became obvious. More than half of the 5.2 million immigrant scientists, mathematicians and engineers currently working in the United States were born in Asia.
“Certain names are associated with specific academic fields and certain heritages tend to target preponderantly science and engineering,” said Grilli. Zhang, for example, is now the most common last name in the U.S. in the fields of chemistry and mathematics. It ranks third in agriculture, geology and physics, but falls to 115th in humanities. Smith, on the other hand, is among the top three in humanities, sociology and medicine, but 20th in chemistry and 47th in geology.
“Sometimes using very simple data can get you expected and unexpected results,” Allesina said. First names can reveal a field’s gender imbalance. They can also fluctuate wildly. The most common first name in the past decade for boys in Italy was Francesco, but that increased by 40 percent following the election of Pope Francis. “It was declining,” Grilli said, “but it bounced back.”
“The good and bad of Italy is the family,” Allesina said. “It protects you from collapse, but it also prevents growth. This really becomes a weight on the shoulders of young people, especially in the South, where many talented students have no choice but to emigrate.”
The National Science Foundation and the Human Frontier Science Program funded this study. Data was provided by Scopus.com.
Tagged: academic hiring, big data, Biological Sciences, Computation Institute, Computational Science, gender imbalance, higher education, Jacopo Grilli, nepotism, racial disparities, stefano allesina
Viruses can infect every kind of life form, from humans all the way down to bacteria. They’ve managed to spread so far and wide because they have a huge bag of tricks for getting inside cells and multiplying. Some viruses can insert genetic material into their hosts, taking over the machinery of its cells to reproduce. Others lay dormant inside a cell for years until some event triggers them to wake up and burst out of the cell to attack others.
One group of viruses, called positive-sense, single-stranded RNA (+RNA) viruses, plays a game of hide and seek to infect a host. Viruses are sometimes classified by the structure of their genetic material—positive-sense, single-stranded RNA viruses have a single strand of RNA that can act like messenger RNA that tells the host cell what proteins make so it can survive. This group accounts for about one-third of all known viruses, including some of the most well-known, disease-causing viruses out there: hepatitis C, West Nile, dengue, Zika and rhinoviruses that cause the common cold.
When a +RNA virus gets inside a cell, it manipulates the membrane of the cell to create a little compartment, called a replication complex. This compartment helps it hide from the immune system so it can replicate and move on to infect other cells.
Seungmin Hwang, PhD, an assistant professor of pathology at the University of Chicago, studies another common +RNA virus, norovirus. Norovirus is a major cause of what we call “stomach flu” or food poisoning, especially in the winter months. In 2012, while working as a postdoc with the mouse version of norovirus, Hwang discovered that the immune system can detect the replication complex where viruses are hiding inside the cell membrane and attack it. At that point, he didn’t know exactly how this worked, but when studying other +RNA viruses he saw the same thing: Somehow, the immune system could “see” the virus in its hiding spot and go after it.
In a new paper published this week in the journal Cell Host & Microbe, Hwang and his team unravel a little bit more of the mystery about how the immune system can sniff out these replication complexes. Just like a household or working office, cells regularly produce trash that needs to be thrown out or recycled. They use a process called autophagy to identify broken down components and unused proteins and wrap them up for disposal. Cells use autophagy proteins to wrap the trash in a membrane-like structure—i.e. its own little garbage bag—and mark it with another autophagy protein so the cell knows to dispose of it.
In the new study, Hwang and his team found that cells use the same autophagy proteins to flag replication complexes where viruses are hiding so the immune system can target them. It’s like marking some trash for regular recycling, and some of it as hazardous materials for special processing. Just how the immune system distinguishes between regular cellular trash and viruses in hiding isn’t clear yet, but the researchers found that this same process works in other +RNA viruses too.
Learning more about how the immune system identifies certain types of viruses could be a big help to researchers developing anti-viral treatments. What’s more intriguing, Hwang says, is that other pathogens that aren’t viruses, like the parasite that causes toxoplasmosis and the bacteria that causes tuberculosis, also build compartments inside cells to hide from the immune system. If scientists can figure out how to target +RNA viruses, it may lead to new ways to fight these diseases too.
“We have broad-spectrum antibiotics to kill bacteria, but there’s nothing like that for viruses because they know how to survive inside our body,” Hwang said. “If what we found holds true for all other viruses, one day we may come up with a solution that would work against all positive RNA viruses and pathogens that hide inside membranous shelters, because that’s a common feature.”
Tagged: Biological Sciences, immunology, Infectious Disease, Microbiology, norovirus, pathology, Seungmin Hwang, toxoplasmosis, viruses
Neuroscientists from the University of Chicago have developed a computer model that can simulate the response of nerves in the hand to any pattern of touch stimulation on the skin. The tool reconstructs the response of more than 12,500 nerve fibers with millisecond precision, taking into account the mechanics of the skin as it presses up against and moves across objects.
The software will allow scientists to see how entire populations of nerve fibers respond when we interact with objects. This model will allow scientists to better understand how the nerve responds to touch, and can be used to build realistic sensations into bionic hands for amputees.
“Almost everything we know about how the nerve responds to stimulation on the skin of the hand is built into this model,” said Sliman Bensmaia, PhD, associate professor of organismal biology and anatomy at the University of Chicago, and principal investigator for the new research. “Finally, you can see how all these nerve fibers work together to give rise to touch.”
Details of the model were published this week in the Proceedings of the National Academy of Sciences. The study, led by postdoctoral scholars Hannes Saal and Benoit Delhaye, along with Brandon Rayhaun, a former undergraduate in the lab, builds upon years of research by Bensmaia’s team on how the nervous system and brain perceive the sense of touch.
Previously, researchers had to conduct costly and time-consuming experiments with animals or human subjects to see how the nervous system responds to a given touch stimulus. Even then, they could only record responses from one neuron at a time. But the sensation of touch comes from thousands of nerve fibers responding in concert as the hand touches, holds, and manipulates objects. The responses of individual nerve fibers aren’t enough to convey stimulus information by themselves. Rather, information about objects we grasp is distributed over large groups of touch-sensitive nerves working together.
Video: Animation showing nerve responses on the fingertip (left) as a flat, rectangular object presses into the skin, then pulls away (right). Each column of the fingertip responses on the left shows responses from a different type of nerve fiber. The top row shows responses when the object is oriented horizontally; the bottom row, vertically.
For instance, when you hold a cell phone in your hand, some of the nerve response is driven by skin receptors located where the edges of the phone press into your fingertips. But skin deformations also radiate away from this area, down the fingers, and throughout the rest of the hand, activating many other receptors in the process. The simulation reveals how interacting with an object creates these unique, detailed patterns of nerve activity.
In addition to its impact on the basic understanding of how these sensations work, the model is also a foundation for restoring touch in bionic hands for amputees. To achieve realistic feelings of touch, neural engineers try to reproduce the natural patterns of nerve activity generated when we manipulate objects. The computer model provides engineers with the nerve output generated by a given stimulus, which can then be recreated in a prosthetic by electrically stimulating the nerve through an interface implanted in the body.
Bensmaia and his team validated the output of the model against data from a wide variety of experiments conducted by other research teams, and show that it matches their output with millisecond precision. The software will be available as a free download, so other engineers can begin using it in their own work.
“Using a model to reproduce a biological system precisely is challenging, and we have been working on this simulation for a very long time. But the final product, I think, is worth it,” Bensmaia said. “It’s a tool that will yield insights that were previously unattainable.”
Tagged: artificial touch, Biological Sciences, neuroprosthetics, Neuroscience, Sliman Bensmaia, touch
From hands on work in a molecular biology lab to collecting marine specimens off the coast of Cape Cod, 13 science and health journalists recently got a taste of life as a scientist through the Logan Science Journalism Fellowships from the Marine Biological Laboratory (MBL), an international center for biological and environmental research and education and an affiliate of the University of Chicago.
Now in its 31st year, the Logan Science Journalism Program (SJP) allows established science and health journalists to “step into the shoes of the scientists they cover” through immersion in hands-on research at the MBL and its affiliates. This year’s program also gave four of the journalists an opportunity to spend four days in Chicago interacting with researchers affiliated with The Microbiome Center, Argonne National Laboratory, the Field Museum and Shedd Aquarium.
During their day at UChicago, they spoke to several researchers about their work, toured the Gnotobiotic Mouse Facility used for conducting germ-free microbiome research, and visited the Polsky Center’s Fabrication Lab and its tools for building 3D prototypes.
Over the years, the Logan Science Journalism Program has granted fellowships to hundreds of journalists from prominent news organizations, including The New York Times, The Wall Street Journal, Science, National Public Radio, The Washington Post, USA Today, CNN, and Scientific American.
Tagged: Biological Sciences, Marine Biological Laboratory, microbiome, Microbiome Center
The Llewellyn John and Harriet Manchester Quantrell Awards, believed to be the nation’s oldest prize for undergraduate teaching, reflect UChicago’s commitment to honor inspiring teachers. The Faculty Award for Excellence in Graduate Teaching and Mentoring recognizes tenure-track and tenured faculty in the Biological Sciences, Divinity School, Humanities, Institute for Molecular Engineering, Physical Sciences, and Social Sciences.
This year, Bana Jabri, professor of medicine and pediatrics, was named one of four Quantrell Award winners, and Jason MacLean, associate professor of neurobiology, won one of five Graduate Teaching Awards. Learn more about their approach to teaching–and listen to them describe the experience in their own words–below:
Bana Jabri likes to compare her teaching method to a cubist painting.
“At the beginning of the course, I introduce different elements for which students don’t necessarily see a meaning or a global image,” she said. “I tell them they have to trust me, that it’s not done randomly, but that it’s part of how we think scientifically.”
Jabri structures her courses in immunology and immunopathology so that students can build a foundation on the basic concepts without getting lost in the details. She says her somewhat old-fashioned method of using a whiteboard instead of computer slides in class sometimes unsettles students, but it helps her avoid overloading them with too much information too quickly.
Her goal is not only to help them master the fundamentals, but also give them the confidence that they can contribute their own ideas.
“Initially they are very scared because they think they cannot do it,” Jabri said. “But the one thing they learn—and it’s absolutely key for me that they take out of class—is that however young, one can have an outstanding idea.”
While it would be easy for a busy scientist to settle on a routine format for the courses he teaches, Jason MacLean changes them every year.
“Frankly, I’m never satisfied, because I think you can always do better,” he said.
MacLean learned to constantly re-examine and critically evaluate his work while studying with his PhD advisor, neurologist Brian Schmidt at the University of Manitoba, Canada.
“Each time I thought that I had a solid result, Brian would poke holes in my conclusion and would force me, either through argument or additional experiments, to convince him of its validity,” MacLean said. “While difficult in the end, it made me a much better scientist.”
MacLean builds this spirit of challenging assumptions and conclusions into both his laboratory and his undergraduate courses in neuroscience. He wants graduate students in the lab to be open-minded and not be constrained by the tenets of neuroscience. In his undergraduate course, he guides students through contemporary literature and asks them to critically evaluate the data and conclusions.
He wants students to take these critical thinking skills and apply them toward whatever field they decide to pursue.
“Whether they remember anything about the brain or not,” he said, “it’s a great vehicle to teach them to think critically and evaluate evidence.”
Tagged: Bana Jabri, Biological Sciences, celiac disease, Gastroenterology, Jason MacLean, neurobiology, Neuroscience, Pediatrics
A 12-month study mapping bacterial diversity within a hospital — with a focus on the flow of microbes between patients, staff and surfaces — should help hospitals worldwide better understand how to encourage beneficial microbial interactions and decrease potentially harmful contact.
“The Hospital Microbiome Project is the single biggest microbiome analysis of a hospital performed, and one of the largest microbiome studies ever,” said study author Jack Gilbert, PhD, director of the Microbiome Center and professor of surgery at the University of Chicago and group leader in Microbial Ecology at Argonne National Laboratory.
“We’ve created a detailed map, highly relevant to clinical practice, of microbial exchange and interaction in a large hospital environment,” he said. “This describes the ecology of a building, a thriving microbial ecosystem that regularly interacts with patients in a seemingly benign way – at least most people don’t appear to be negatively affected. It gives us a framework, something we can build on, showing how microorganisms enter and colonize a hospital environment.”
The study, “Bacterial colonization and succession in a newly opened hospital,” began two months before the University of Chicago Medicine opened its new hospital, the Center for Care and Discovery, on Feb. 23, 2013, and continued for 10 months afterward. The researchers collected more than 10,000 samples. They were able to detect microbial DNA in 6,523. These came from 10 patient care rooms and two adjoining nursing stations, one caring for surgical patients and the other, on a different floor, for cancer patients.
The investigators swabbed each patient’s hand, nostril and armpit, as well as the surfaces patients may have touched, such as bedrails or faucet handles. They collected additional room samples from multiple surfaces, including the floor and the air filter. Each room was cleaned daily, with a more extensive cleaning after each patient’s discharge.
The researchers also gathered samples from each unit’s nursing staff, swabbing their hands, gloves, shoes, nursing station countertops, pagers, shirts, chairs, computers, land lines and cell phones.
The most obvious change came when the hospital opened, which followed extensive cleaning efforts. Bacterial organisms such as Acinetobacter and Pseudomonas, abundant during construction and pre-opening preparations, were quickly replaced by human skin-associated microbes such as Corynebacterium, Staphylococcus and Streptococcus, brought in by patients.
“Before it opened, the hospital had a relatively low diversity of bacteria,” Gilbert said. “But as soon as it was populated with patients, doctors and nurses, the bacteria from their skin took over.”
A second, and ongoing, set of changes followed each patient’s hospital admission. On a patient’s first day in the hospital, microbes tended to move from surfaces in the patient’s room — bedrails, countertops, faucet handles — to the patient. But by the next and every subsequent day, the preponderance of microbes moved in the other direction, from the patient to the room, steadily adding to the microbial diversity of the surfaces in the room.
“By the second day of their stay,” Gilbert said, “the route of microbial transmission was reversed. Within 24 hours, the patient’s microbiome takes over the hospital space.”
There were two unanticipated findings. First, when the heat and humidity increased during the summer, staff members shared more bacteria with each other. Second, when they measured the impact of treatments — such as antibiotics prior to or during admission, chemotherapy during admission, surgery, or admission to the hospital though the emergency department — the impact was minimal.
“We consistently found that antibiotics given intravenously or by mouth had almost no impact on the skin microbiome,” Gilbert said. “But when a patient received a topical antibiotic, then, as expected, it wiped out the skin microbes.”
Samples from the rooms of 92 patients who had longer hospital stays, measured in months, revealed a trend. Some potentially harmful bacteria, such as Staphylococcus aureus and Staphylococcus epidermidis, faced with continual selective pressure, managed to acquire genes that could boost antibiotic resistance and promote host infection.
“This requires further study,” Gilbert said, “but if it proves to be true then these genetic changes could affect the bacteria’s ability to invade tissue or to escape standard treatments.”
The study, published May 24 in Science Translational Medicine, “demonstrates the extent to which the microbial ecology of patient skin and of hospital surfaces are intertwined and may provide context to future studies of the transmission of hospital-acquired infections,” the authors conclude.
The study was funded by the Alfred P. Sloan Foundation Microbiology of the Built Environment Program and the United States Department of Energy. Additional authors were Simon Lax, Naseer Sangwan, Peter Larsen, Kim M Handley, Miles Richardson, John Alverdy, Kristina Guyton, Monika Krezalek, Benjamin Shogan, Jennifer Defazio, Irma Flemming, Baddr Shakhsheer, Stephen Weber, Emily Landon and Sylvia Garcia-Houchins from the University of Chicago and/or Argonne National Laboratory; Daniel Smith from Baylor College of Medicine; Jeffrey Siegel from the University of Toronto; Rob Knight from the University of California, San Diego; and Brent Stephens from the Illinois Institute of Technology.
Tagged: bacteria, Biological Sciences, Hospital Microbiome Project, Infectious Disease, Jack Gilbert, microbiome
$100 million gift establishes Duchossois Family Institute to develop ‘new science’ focused on optimizing health
A Chicago-area family with a deep commitment to supporting science and medicine is giving $100 million to establish The Duchossois Family Institute at the University of Chicago Medicine, which seeks to accelerate research and interventions based on how the human immune system, microbiome and genetics interact to maintain health.
The gift from The Duchossois Group Inc. Chairman and CEO Craig Duchossois, his wife, Janet Duchossois, and The Duchossois Family Foundation will support development of a “new science of wellness” aimed at preserving health and complementing medicine’s traditional focus on disease treatment. Their investment will help build an entrepreneurial infrastructure that stimulates research, data integration, and clinical applications, while educating the next generation of young physicians and students in this new science.
By providing resources and research infrastructure, The Duchossois Family Institute: Harnessing the Microbiome and Immunity for Human Health will allow faculty and students to focus on preventing disease by optimizing the body’s own defenses and finding new ways to maintain well-being. With the embedded expertise of the university’s Polsky Center for Entrepreneurship and Innovation, they will work aggressively to bring breakthroughs to market through partnerships with industry, venture capitalists, government agencies, like-minded philanthropists, and the public.
“The Duchossois Family Institute will draw on the creativity and skill of university researchers across many fields in bringing new perspectives to medical science, oriented toward making an impact that greatly benefits human lives,” said University of Chicago President Robert J. Zimmer. “We are grateful for the Duchossois family’s remarkable level of engagement in establishing this innovative alliance between medical experts and entrepreneurs.”
The amount is the largest single gift in support of UChicago Medicine and brings the family’s lifetime charitable contributions to the academic medical center to $137 million. Ludwig Institute for Cancer Research has donated a total of $118 million since 2006, largely to support cancer research.
The Duchossois gift is also the fourth time there has been a single gift of $100 million or more to the University of Chicago. The Thomas L. Pearson and The Pearson Family Members Foundation made a grant of $100 million in 2015 to establish The Pearson Institute for the Study and Resolution of Global Conflicts and The Pearson Global Forum at the Harris School of Public Policy, and an anonymous donor gave $100 million in 2007 to fund the Odyssey Scholarship Program in support of undergraduate student aid. The university’s largest gift to date is $300 million in 2008 from investment entrepreneur David Booth, for whom UChicago’s Booth School of Business is named.‘New science of wellness’
Until now, much of the research on the microbiome — the community of bacteria, fungi, viruses and other microorganisms living in the body, primarily the digestive tract — and its relation to human health has focused on its relationship to disease. Recent discoveries, many at the University of Chicago, demonstrate that the genetic material encoded within the microbiome is a critical factor in fine-tuning the immune system and can be powerful in maintaining well-being and preventing disease. New computer technology to integrate and analyze vast amounts of biological and medical data — pioneered by the National Cancer Institute Genomic Data Commons, developed and operated by the university — also is allowing researchers from disparate disciplines and locations to work toward common interests and solutions.
The Duchossois (pronounced DUCH-ah-swah) family wanted to support the application of these discoveries to improve health, and turned to leaders at the University of Chicago for ideas.
“We wanted to find a way to be transformative in our giving and looked to the University of Chicago and asked, ‘What is the nature of what’s in our bodies that helps us stay well?’” said Ashley Duchossois Joyce, president of The Duchossois Family Foundation. “They came back with an answer that connected all the dots, confirming the potential for a new science of wellness that fundamentally explores how the immune system and microbiome interact.”
Focusing on factors crucial to maintaining wellness could greatly expand the tools available to medical researchers and entrepreneurs. Early targets identified by institute scientists envision a potential future in which:
- Peanuts, milk and eggs could safely return to school menus.
- Children with asthma play outside, confident they can breathe without inhalers.
- Inexpensive sensors help families adjust their homes to optimize health.
- Doctors guide patients to foods and probiotics to win the fight against obesity.
- Technologies pinpoint the microbes needed to treat and prevent autoimmune diseases.
- Probiotics and prebiotics improve the effectiveness of cancer and antidepressant drugs.
- Judiciously used antibiotics reduce the impact of Alzheimer’s disease.
The institute will build on insights already gained from research at the University of Chicago.
“The family recognized the university’s and medical center’s leadership in genomics, the human immune system, data analytics and the microbiome,” said T. Conrad Gilliam, dean for basic science in the Division of the Biological Sciences, who will lead efforts to launch the institute. “The new institute will integrate these areas into this new science focused on longstanding health and the body’s natural ability to maintain wellness.”
The Duchossois Family Institute will support leading-edge technologies and services including:
- A clinical repository to maintain biological samples
- Microbial cultivation and analysis tools
- Next-generation platform to identify biomarkers that mediate between the microbiome and immune system
- Medicinal chemistry to pinpoint biomarkers and develop more effective therapies
- High-throughput genetic sequencing for microbial DNA
- A data commons for sharing large amounts of microbial, environmental and medical information
The Duchossois Family Institute’s efforts will bring together investigators across the University of Chicago as well as affiliates at Argonne National Laboratory, Marine Biological Laboratory at Woods Hole, Mass., and eventually many more partners.
In addition, the university will embed commercialization specialists from its Polsky Center for Entrepreneurship and Innovation within the institute to promote participation and support of the business community to further accelerate innovation. Polsky’s proven expertise will ensure that the intellectual property generated is protected, licensed, and potentially spun off for business development for the benefit of participating institutions and the entire region.
“Sustainability and entrepreneurship are critical to the success of this new endeavor,” said Craig Duchossois, a longtime trustee of both the university and the medical center. “The fact that we are able to leverage so many resources at one university means we can aggressively advance the progress of this new science and help society.”A history of giving
The latest gift continues a history of giving to UChicago that spans 37 years, inspired by the care that Beverly Duchossois, late wife of Richard Duchossois, received at what was then called the University of Chicago Hospital. In 1980, Richard Duchossois established the Beverly E. Duchossois Cancer Fund in memory of his wife.
In the years since, the family has given the University a total of $37 million to drive innovation and transformative care at the medical center, including a named professorship and several cancer research funds. That amount includes a $21 million gift in 1994 to establish the Duchossois Center for Advanced Medicine, which is home to outpatient specialty clinics, diagnostic centers and treatment facilities at the University of Chicago Medicine.
“We are honored and privileged to be the beneficiary of such enormous generosity and are excited by what the science can accomplish,” said Kenneth S. Polonsky, MD, dean of the Division of the Biological Sciences and the Pritzker School of Medicine and executive vice president of medical affairs. “The gift invests in a core strength of UChicago Medicine: our basic science research and our ability to quickly translate that research for the benefit of patients.”
In addition to Craig Duchossois’ service as a trustee, Janet Duchossois serves as a member of the University of Chicago Women’s Board. The Duchossois Family Foundation is made up of family members spanning three generations including patriarch Richard; son and daughter-in-law, Craig and Janet; daughters Kimberly Duchossois, a University of Chicago Cancer Research Foundation board member, and Dayle Fortino; and grandchildren, including Ashley Duchossois Joyce, a University of Chicago graduate and former member of the School of Social Service Administration Visiting Committee, Jessica Swoyer Green and Ilaria Woodward.Press Kit
Additional information, including facts about the Duchossois Family Institute and quotes from the Duchossois family, UChicago leadership and faculty:
For media inquiries, please contact the University of Chicago Medicine news office.About the University of Chicago Medicine
The University of Chicago Medicine & Biological Sciences is one of the nation’s leading academic medical institutions. It comprises the Pritzker School of Medicine, a top U.S. medical school; the University of Chicago Biomedical Sciences Division; and the University of Chicago Medical Center. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine.About The Duchossois Family Foundation
Established in 1984 by first- and second-generation family members, The Duchossois Family Foundation strives to empower individuals to enhance their quality of life through wellness and education. Visit their website at TheDFF.org.
Tagged: big data, Biological Sciences, Genetics, immune system, immunology, microbiome, philanthropy, The Duchossois Family Institute
Analysis of a 3.3 million-year-old fossil skeleton reveals the most complete spinal column of any early human relative, including vertebrae, neck and rib cage. The findings, published this week in the Proceedings of the National Academy of Sciences, indicate that portions of the human spinal structure that enable efficient walking motions were established millions of years earlier than previously thought.
The fossil, known as “Selam,” is a nearly complete skeleton of a 2½ year-old child discovered in Dikika, Ethiopia in 2000 by Zeresenay (Zeray) Alemseged, professor of organismal biology and anatomy at the University of Chicago and senior author of the new study. Selam, which means “peace” in the Ethiopian Amharic language, was an early human relative from the species Australopithecus afarensis—the same species as the famous Lucy skeleton.
In the years since Alemseged discovered Selam, he and his lab assistant from Kenya, Christopher Kiarie, have been preparing the delicate fossil at the National Museum of Ethiopia. They slowly chipped away at the sandstone surrounding the skeleton and used advanced imaging tools to further analyze its structure.
“Continued and painstaking research on Selam shows that the general structure of the human spinal column emerged over 3.3 million years ago, shedding light on one of the hallmarks of human evolution,” Alemseged said. “This type of preservation is unprecedented, particularly in a young individual whose vertebrae are not yet fully fused.”
Many features of the human spinal column and rib cage are shared among primates. But the human spine also reflects our distinctive mode of walking upright on two feet. For instance, humans have fewer rib-bearing vertebrae – bones of the back – than those of our closest primate relatives. Humans also have more vertebrae in the lower back, which allows us to walk effectively. When and how this pattern evolved has been unknown until now because complete sets of vertebrae are rarely preserved in the fossil record.
“For many years we have known of fragmentary remains of early fossil species that suggest that the shift from rib-bearing, or thoracic, vertebrae to lumbar, or lower back, vertebrae was positioned higher in the spinal column than in living humans. But we have not been able to determine how many vertebrae our early ancestors had,” said Carol Ward, a Curator’s Distinguished Professor of Pathology and Anatomical Sciences in the University of Missouri School of Medicine, and lead author on the study. “Selam has provided us the first glimpse into how our early ancestors’ spines were organized.”
In order to be analyzed, Selam had to take a trip. She traveled to the European Synchrotron Radiation Facility in Grenoble, France, where Alemseged and the research team used high-resolution imaging technology to visualize the bones.
“This technology provides the opportunity to virtually examine aspects of the vertebrae otherwise unattainable from the original specimen,” said coauthor of the study Fred Spoor, a professor of evolutionary anatomy in the Department of Biosciences at the University College London.
The scans indicated that Selam had the distinctive thoracic-to-lumbar joint transition found in other fossil human relatives, but the specimen is the first to show that, like modern humans, our earliest ancestors had only twelve thoracic vertebrae and twelve pairs of ribs. That is fewer than in most apes.
“This unusual early human configuration may be a key in developing more accurate scenarios concerning the evolution of bipedality and modern human body shape,” said Thierra Nalley, an assistant professor of anatomy at Western University of Health Sciences in Pomona, California, also an author on the paper.
This configuration marks a transition toward the type of spinal column that allows humans to be the efficient, athletic walkers and runners we are today.
“We are documenting for the first time in the fossil record the emergence of the number of the vertebrae in our history, when the transition happened from the rib-bearing vertebrae to lower back vertebrae, and when we started to extend the waist,” Alemseged said. “This structure and its modification through time is one of the key events in the history of human evolution.”
The study, “Thoracic Vertebral Count and Thoracolumbar Transition in Australopithecus afarensis” was supported by Margaret and Will Hearst, the National Science Foundation and the European Synchrotron Radiation Facility.
Jeff Sossamon from the University of Missouri contributed to this story
Tagged: Biological Sciences, Ethiopia, Evolution, fossils, human evolution, paleoanthropology, paleontology, Selam, Zeray Alemseged
In 2015, scientists announced they had discovered 15 skeletons of an unusual new species of human cousins, clustered together deep in a remote chamber of the Rising Star cave system in South Africa. Homo naledi, as the species was named, was an enigma to researchers. Some of its features, like its long legs, small teeth and dexterous wrists, resembled modern humans; but its small brain size and curved fingers suggested it was more closely related to our ape-like Australopithecus ancestors.
This week we have one answer about the history of these fossils: how old they are. In a series of papers published in the journal eLife, a team led by Professor Lee Berger of The University of the Witwatersrand in Johannesburg, South Africa, announced that the Homo naledi fossils are between 335,000 and 236,000 years old. That means these primitive, long-lost cousins lived at the same time as Homo sapiens, the first time it has been shown that another species of hominin survived alongside the first humans in Africa.
Myra Laird, a postdoctoral scholar at the University of Chicago, worked on the project, studying the features of the Homo naledi skulls and comparing them to other fossils to determine whether a new set of specimens, found in second cave near the original site, were of the same species. She began the work as a graduate student at New York University, and continued after she moved to UChicago, where she also published a paper about the skull in the Journal of Human Evolution last fall.
One of the most memorable moments, Laird said, was putting together the face of Neo, one of the newly discovered skulls.
“Fossil hominins rarely preserve the face because the bones are quite fragile, so it was really exciting when my colleagues and I finally pieced together the bones of the face,” she said. “We all stood back and just stared for a couple of minutes. It was like fitting the final piece into a complicated puzzle.”
Tagged: Biological Sciences, Evolution, Homo naledi, Myra Laird, paleoanthropology, paleontology
Neil H. Shubin, PhD, the Robert R. Bensley Distinguished Service Professor of Organismal Biology and Anatomy and Associate Dean for Academic Strategy at the University of Chicago, has been elected to the American Philosophical Society. Members are nominated and elected by their peers in the Society.
Founded by Benjamin Franklin in 1743, the APS is the nation’s oldest learned society. An eminent, internationally known scholarly organization, the American Philosophical Society “promotes useful knowledge in the sciences and humanities through excellence in scholarly research.”
Shubin was elected for his discoveries involving the evolution of limbs and the transition from water to dry land. One of his most significant discoveries, the 375-million-year-old Tiktaalik roseae fossil, is an important transitional form between fish and land animals.
Shubin, Who was elected to the National Academy of Sciences in 2011, has written two popular science books: the best-selling “Your Inner Fish” (2008), named best book of the year by the National Academy of Sciences and made into a celebrated PBS series, and “The Universe Within: The Deep History of the Human Body” (2013). He spent much of last December and January hunting for fossils in Antarctica.
Two other current or former University of Chicago faculty members were also elected to the APS this year: Michael S. Turner, the Bruce V. and Diana M. Rauner Distinguished Service Professor and director of the Kavli Institute for Cosmological Physics; and former law school senior lecturer, Barack Obama, the 44th President of the United States.
Tagged: American Philosophical Society, Biological Sciences, Evolution, Neil Shubin, paleontology