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More and more students are graduating with their bachelor’s degrees and taking a gap year, a period of time before jumping into a postgraduate program. A new grant from the American Cancer Society will help the UNM Comprehensive Cancer Center introduce these students to scientific research.
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University of New Mexico Comprehensive Cancer Center
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Newswise — The Center for Bioenergy Innovation has been renewed by the Department of Energy as one of four bioenergy research centers across the nation to advance robust, economical production of plant-based fuels and chemicals. CBI, led by Oak Ridge National Laboratory, is focused on the development of nonfood biomass crops and specialty processes for the production of sustainable jet fuel to help decarbonize the aviation sector.
The DOE announcement provides $590 million to the centers over the next five years. Initial funding for the four centers will total $110 million for Fiscal Year 2023. Outyear funding will total up to $120 million per year over the following four years, contingent on availability of funds.
“To meet our future energy needs, we will need versatile renewables like bioenergy as a low-carbon fuel for some parts of our transportation sector,” said U.S. Secretary of Energy Jennifer M. Granholm. “Continuing to fund the important scientific work conducted at our Bioenergy Research Centers is critical to ensuring these sustainable resources can be an efficient and affordable part of our clean energy future.”
CBI’s national laboratory, university and industry partners will take a multipronged, accelerated approach over the next five years to producing sustainable jet fuel. Focus areas include:
CBI intends to reach Tier 1 validation of its jet biofuel, an aviation industry standard that determines the fuel’s properties are fit-for-purpose in existing and future airplane fleets. The development of renewable fuels is a key strategy to reduce carbon dioxide emissions from commercial aircraft.
“Our researchers are excited to apply the best of biology and chemistry and create sustainable jet fuel to help clean up our skies and stimulate a thriving bioeconomy,” said ORNL’s Jerry Tuskan, CBI chief executive officer. “CBI’s feedstocks-to-fuels process will support upgrading carbohydrates and lignin from corn stover, process-advantaged switchgrass and poplar biomass into a tunable portfolio of chemicals for jet biofuel.”
The new centers follow the success of pioneering bioenergy research centers established by DOE’s Office of Biological and Environmental Research within DOE’s Office of Science in 2007.
The ORNL-led CBI and its predecessor, the BioEnergy Science Center, demonstrated significant scientific breakthroughs in their mission to design ideal biomass feedstock crops and microbes to overcome the natural resistance of plants to being broken down and converted into fuels and products. In the last five years, CBI authored or co-authored 449 peer-reviewed journal articles that were cited 12,295 times by the scientific community In the same period CBI generated 57 invention disclosures, 32 patent applications, four license/option agreements and one start-up. The center has also reached more than 310,000 students, parents and teachers as a result of its educational outreach programs.
“CBI’s collaborative science model and foundational success are key to accelerating the innovation needed for widespread, sustainable and profitable production of jet fuel from lignocellulosic feedstocks,” said Stan Wullschleger, ORNL associate laboratory director for Biological and Environmental Systems Science.
“CBI builds on 15 years of success in applying scientific breakthroughs to meet the nation’s energy and decarbonization challenge,” said interim ORNL Director Jeff Smith. “CBI represents the national laboratory system at its best—developing scientific solutions to benefit the nation and inspiring the next generation of scientists through unique educational outreach.”
Current partners in the next generation of CBI with ORNL include the University of Georgia; National Renewable Energy Laboratory; Dartmouth College; University of Maryland Eastern Shore; Brookhaven National Laboratory; Massachusetts Institute of Technology; Poplar Innovations Inc.; Pennsylvania State University; University of California, Davis; University of California San Diego; University of Tennessee; University of Wisconsin–Madison; University of Virginia; Washington State University; and France’s National Research Institute for Agriculture, Food and Environment.
UT-Battelle manages ORNL for DOE’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov/.
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Oak Ridge National Laboratory
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Newswise — URBANA, Ill. — The U.S. Department of Energy (DOE) has committed another round of funding to the University of Illinois Urbana-Champaign to lead the second phase of its Bioenergy Research Center — one of four large-scale DOE-funded research centers focused on innovation in biofuels, bioproducts, and a clean energy future for the country.
Earlier today the DOE announced a five-year extension of funding for the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), to a total of $237.9 million for the period from 2017 to 2027. CABBI is a collaboration between the university’s Institute for Sustainability, Energy, and Environment (iSEE); the Carl R. Woese Institute for Genomic Biology (IGB); 11 academic departments across the Illinois campus, including five in the College of Agricultural, Consumer and Environmental Sciences (ACES); and 20 partner institutions across the nation.
“To meet our future energy needs, we will need versatile renewables like bioenergy as a low-carbon fuel for some parts of our transportation sector,” U.S. Secretary of Energy Jennifer M. Granholm said in the DOE news release. “Continuing to fund the important scientific work conducted at our Bioenergy Research Centers is critical to ensuring these sustainable resources can be an efficient and affordable part of our clean energy future.”
Andrew Leakey, Professor and Head of the Department of Plant Biology at Illinois, will continue as Director of CABBI, a position he has held since 2020.
“Energy independence has become an increasingly important security issue for the United States, and CABBI will continue to provide breakthroughs toward a new generation of sustainable, cost-effective biofuels and bioproducts that will replace fossil fuel-based products,” Leakey said. “This grant represents a massive investment in CABBI and its diverse team of scientists. We are committed to help push the U.S. toward a new bio-based economy.”
Under the funding extension, Emily Heaton, a Professor of Regenerative Agriculture in the Department of Crop Sciences at ACES, will continue to lead the Feedstock Production theme at CABBI. Her team, which includes seven other ACES faculty from Crop Sciences, uses the “plants as factories” paradigm, in which biofuels, bioproducts, and foundation molecules for conversion are grown directly in crops that are resilient and productive.
“This award advances our capacity to protect and enhance the natural resource base on which all life depends by using resilient plants for power, fuel, and products,” Heaton said. “The science and practices being developed by CABBI and our collaborators will translate into secure domestic energy with climate benefits. I am excited we can also use this funding to complement our corn/soy agriculture with strategically placed perennial bioenergy crops, bringing cleaner air and water, healthier soil, and good new jobs for our rural communities.”
The two other CABBI themes, Conversion and Sustainability, are also stacked with lead scientists from ACES departments. Those teams focus on turning plants into high-value chemicals and ensuring a sustainable environmental and economic bottom line, respectively.
Madhu Khanna, Alvin H. Baum Family Fund Chair, Director of iSEE, a CABBI Sustainability Theme researcher, and Professor in the ACES Department of Agricultural and Consumer Economics, said iSEE is excited to support CABBI research in partnership with IGB and with the College ACES to enable cutting-edge research at the 320-acre Illinois Energy Farm — “a unique living laboratory that enables researchers to grow trials of promising biofuel feedstocks at the field scale” — and other partner sites.
“One of the world’s major challenges is to provide sustainable sources of energy that meet societal needs as the population continues to grow,” Khanna said, “and Illinois is uniquely qualified to help lead that challenge” with the world-class facilities at IBRL and at IGB — the latter of which oversees and integrates CABBI’s core science team under one roof.
Said IGB Director Gene E. Robinson: “The IGB has over 15 years of experience in successfully addressing grand challenges by transdisciplinary integration of the life sciences, physical sciences, social sciences, and engineering, and we are proud to host the CABBI team. Our partnership with iSEE has been a successful one for five years, and we look forward to five more years of breakthrough discoveries.”
Susan Martinis, the Vice Chancellor for Research and Innovation at Illinois and Chair of CABBI’s Governance Board, noted the university’s strong DOE research portfolio, which is regularly among the top five in the nation. The Center is one of four DOE Bioenergy Research Centers (BRCs), joining the Great Lakes Bioenergy Research Center (GLBRC) led by the University of Wisconsin and Michigan State University, the Center for Bioenergy Innovation (CBI) led by the Oak Ridge National Laboratory, and the Joint BioEnergy Institute (JBEI) led by Lawrence Berkeley National Laboratory.
“The unique partnership between our research institutes and interdisciplinary collaboration across academic disciplines are hallmarks of research at Illinois,” Martinis said. “IGB and iSEE have built an infrastructure in fields, labs, and virtual environments to allow researchers to do what they do best: solve the world’s most pressing problems. For the CABBI team, that means uniting experts nationwide in agriculture, engineering, genomics, biology, chemistry, economics, and more to deliver on the promise of bioenergy and bioproducts innovation.”
Phase II partner institutions include Brookhaven (N.Y.) National Laboratory; Lawrence Berkeley National Laboratory in Berkeley, Calif.; Lawrence Livermore National Laboratory in Livermore, Calif.; HudsonAlpha Institute for Biotechnology in Huntsville, Ala.; the U.S. Department of Agriculture’s (USDA) Agricultural Research Service (ARS) in Houma, La., Peoria, Ill., and Urbana, Ill.; Alabama A&M University (new addition for Phase II); Colorado State University; Iowa State University; Mississippi State University; Penn State University; Princeton (N.J.) University; Texas A&M University; University of California-Berkeley; University of Florida; University of Minnesota-Twin Cities; University of Nebraska-Lincoln; the University of Wisconsin-Madison; and West Virginia University.
The Center employs nearly 60 faculty-level researchers — including seven from underrepresented groups who were added since the founding in 2017 — more than 160 postdoctoral researchers and technicians, 90 graduate students, and 50 undergraduates, and 15 support staff. Diversity, equity, and inclusion efforts include a paid summer research internship for undergraduates from underrepresented groups in STEM, and efforts are underway to find corporate and philanthropic funding to expand that program during Phase II.
“One of the best ways for our nation to strengthen our competitiveness with the rest of the world is to enhance the brilliance that already exists right here in Illinois,” U.S. Sen. Tammy Duckworth, D-Ill., said in the DOE news release. “I’m pleased that the University of Illinois at Urbana-Champaign’s Center for Advanced Bioenergy and Bioproducts Innovation will receive this federal funding to help support groundbreaking research on clean energy, create jobs, address climate change and further secure Illinois’s place as a global leader.”
Added U.S. Rep. Nikki Budzinski, D-Ill.: “As a graduate of the University of Illinois and its proud representative in Congress, I’m honored to join Secretary Granholm in announcing $590 million that will benefit bioenergy research at my alma mater. For the last five years, the University of Illinois has done groundbreaking research at the Center for Advanced Bioenergy and Bioproducts Innovation to revolutionize the role of biofuels and agriculture in our 21st century energy economy. I’m so glad to see funding for this project renewed for the next five years, and I look forward to seeing how these resources will benefit family farmers, our environment, and rural communities across central and southern Illinois.”
The BRC Program was established in 2007 and, in total, led to 4,452 peer-reviewed publications, 845 invention disclosures, 715 patent applications, 298 licenses or options, 261 patents, and 22 start-up companies as of August 2022. Learn more at science.energy.gov.
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University of Illinois Urbana-Champaign College of Agricultural, Consumer and Environmental Science (ACES)
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Newswise — Researchers in China have successfully restored the vision of mice with retinitis pigmentosa, one of the major causes of blindness in humans. The study, to be published March 17 in the Journal of Experimental Medicine, uses a new, highly versatile form of CRISPR-based genome editing with the potential to correct a wide variety of disease-causing genetic mutations.
Researchers have previously used genome editing to restore the vision of mice with genetic diseases, such as Leber congenital amaurosis, that affect the retinal pigment epithelium, a layer of non-neuronal cells in the eye that supports the light-sensing rod and cone photoreceptor cells. However, most inherited forms of blindness, including retinitis pigmentosa, are caused by genetic defects in the neural photoreceptors themselves.
“The ability to edit the genome of neural retinal cells, particularly unhealthy or dying photoreceptors, would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases such as retinitis pigmentosa,” says Kai Yao, a professor at the Wuhan University of Science and Technology.
Retinitis pigmentosa can be caused by mutations in over 100 different genes and is estimated to impair the vision of 1 in 4,000 people. It begins with the dysfunction and death of dim light-sensing rod cells, before spreading to the cone cells required for color vision, eventually leading to severe, irreversible vision loss.
Yao and colleagues attempted to rescue the vision of mice with retinitis pigmentosa caused by a mutation in the gene encoding a critical enzyme called PDE6β. To do this, Yao’s team developed a new, more versatile CRISPR system called PESpRY, which can be programmed to correct many different types of genetic mutation, regardless of where they occur within the genome.
When programmed to target the mutant PDE6β gene, the PESpRY system was able to efficiently correct the mutation and restore the enzyme’s activity in the retinas of mice. This prevented the death of rod and cone photoreceptors and restored their normal electrical responses to light.
Yao and colleagues performed a variety of behavioral tests to confirm that the gene-edited mice retained their vision even into old age. For example, the animals were able to find their way out of a visually guided water maze almost as well as normal, healthy mice and showed typical head movements in response to visual stimuli.
Yao cautions that much work still needs to be done to establish both the safety and efficacy of the PESpRY system in humans. “However, our study provides substantial evidence for the in vivo applicability of this new genome-editing strategy and its potential in diverse research and therapeutic contexts, in particular for inherited retinal diseases such as retinitis pigmentosa,” Yao says.
Qin et al. 2023. J. Exp. Med. https://rupress.org/jem/article-lookup/doi/10.1084/jem.20220776?PR
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About Journal of Experimental Medicine
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Newswise — Researchers from the University of Illinois Chicago hope to learn more about how the human immune system is regulated by the endothelium in lung tissue, thanks to a $13 million, multi-project Program Project Grant award from the National Heart, Lung, and Blood Institute.
The researchers hope that the projects will lead to new avenues for research and treatments to help patients who suffer from conditions like chronic obstructive pulmonary disorder, pulmonary fibrosis and acute respiratory distress disorder, a common and serious complication of COVID-19.
Conditions like these are known to be exacerbated by the body’s own immune response, such as when the inflammation meant to fight infections or heal injuries spirals out of control and winds up inflicting harm.
The researchers think that these inflammatory conditions may be common in the lungs because of unique endothelial cells, which line blood vessels and shield the lungs from trauma and bacterial or viral infections.
“Targeted therapies remain an urgent unmet need. It is now becoming increasingly clear that the lung endothelium is a complex monolayer, an organ itself,” said Dolly Mehta, UIC professor and interim head of the Department of Pharmacology and Regenerative Medicine at the College of Medicine and the program director for the grant.
“Studying this enigmatic immune regulatory function of lung endothelium is crucial for understanding how endothelial cells control immunity and defensive function of the lungs,” she said.
The research team consists of six investigators who will lead three separate project grants and three separate cores.
Mehta is also the principal investigator for one of the projects, for $2.2 million, which supports research on a protein receptor in endothelial cells that promotes lung integrity.
Asrar Malik, professor of pharmacology and regenerative medicine, and Dr. Jalees Rehman, professor and head of the Department of Biochemistry and Molecular Genetics, will lead the other two project grants.
Malik’s lab will look at an enzyme called E3 ligase that influences the integrity of the lining of the blood vessels and the genes that activate the enzyme. Rehman’s lab will look at how mitochondria in endothelial cells can be leveraged to prevent out-of-control inflammation. The awards are $1.8 million and $2.2 million, respectively.
“We know that in tissues like those found in the lung, heart and brain, the blood vessels present a unique and complicated immune environment, and we know that there is an interconnectedness between all the many cellular processes. The idea of this multi-project grant is to help create an infrastructure for collaboration among researchers looking at these various mechanisms,” Mehta said.
Konstantinos Chronis, assistant professor of biochemistry and molecular genetics, will lead the project’s epigenetics and transcriptomics core. Gary Mo, assistant professor of pharmacology and regenerative medicine, will lead the cellular imaging core. Yoshikazu Tsukasaki, a research assistant professor also from the department of pharmacology and regenerative medicine, will lead the intravital imaging and physiology core.
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University of Illinois Chicago
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Newswise — The National Institutes of Health has awarded Rutgers a $3.5 million grant to conduct a five-year study exploring the impact medications have on older adults with multiple medical conditions.
The goal of researchers from Rutgers Center for Pharmacoepidemiology and Treatment Science (PETS) is to provide patients with multiple chronic conditions, caregivers and health care providers with information needed to make informed treatment decisions.
“Unfortunately, most clinical trials of medications do not include patients with multimorbidity, which means that there is little data available about the risks and benefits of medications in this population,” said Chintan Dave, assistant director at PETS and the principal investigator of the National Heart, Lung and Blood Institute grant-backed project. “This lack of information makes it difficult for health care providers to make informed decisions about treating patients with multiple medical conditions.”
Multimorbidity is a common issue for older adults, according to researchers. In the U.S., more than two thirds of adults over the age of 65 have multiple chronic conditions, which can lead to higher health care costs and increased risk of negative health outcomes, including death.
“With over 36 million older adults in the U.S. affected by multimorbidity, this is a pressing issue that requires immediate attention,” said Dave, who also is a core faculty member of the Rutgers Institute for Health, Health Care Policy and Aging Research (IFH) and an assistant professor with Rutgers Ernest Mario School of Pharmacy.
Dave and his colleagues will use data from more than 23 million patients to learn how having multiple conditions affects the benefits and risks of medications, representing the first effort to systematically evaluate the impact of multimorbidity on medication related outcomes. Specifically, researchers will examine medication use and outcomes in three highly prevalent chronic conditions: Type 2 diabetes, atrial fibrillation and atherosclerotic cardiovascular disease.
Coinvestigators involved in the study include Brian Strom, the chancellor of Rutgers Biomedical and Health Sciences; Tobias Gerhard, interim director of IFH and director of PETS; Jason Roy, a professor of biostatistics and chair of the Department of Biostatistics and Epidemiology at the Rutgers School of Public Health; Soko Setoguchi, a core faculty member at PETS and IFH, professor of medicine at Rutgers Robert Wood Johnson Medical School and professor of epidemiology at Rutgers School of Public Health; and Melissa Wei, an assistant professor of medicine in residence at the David Geffen School of Medicine at University of California, Los Angeles.
The grant was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number R01HL163163. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Rutgers University-New Brunswick
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Newswise — UC Davis Comprehensive Cancer Center is partnering with TargaGenix and Northeastern University to study pancreatic ductal adenocarcinoma (PDAC). The often-lethal cancer has an average five-year survival rate of less than 11%. The academic-industry partnership will receive nearly $3 million over five years thanks to National Institutes of Health (NIH) funding through its R01 grant program. The NIH gives R01 grants only to mature research projects driven by strong preliminary data.
The team will develop a treatment based on the novel chemotherapy TGX-1214, in combination with cancer immunotherapy. The researchers expect that by the end of the study, this will become part of a new treatment option for PDAC patients.
PDAC accounts for more than 90% of pancreatic cancer cases. It is usually diagnosed at a late stage when disease has spread to other organs. Symptoms are often common and non-specific, such as lack of appetite and weight loss. By the time symptoms appear, the disease is at a late stage, making it inoperable and incurable.
Current challenges treating pancreatic cancer
“Surgery, which offers the only realistic hope for a cure, is a viable option in only a limited number of patients, and current chemotherapy and radiation therapy offer limited or no benefit at all,” UC Davis pancreatic cancer researcher Gerardo Mackenzie said.
Mackenzie is an associate professor in the Department of Nutrition. He and UC Davis oncologist and Medical Director of the cancer center’s Office of Clinical Research Edward J. Kim are the UC Davis principal investigators for the study.
“The current chemotherapy combinations used to treat PDAC have marginally improved survival outcomes. The average survival in advanced disease is still less than a year. The limited benefit of these therapies, unfortunately, comes at the cost of significant toxicities, including suppressed immune system, fatigue, nausea, diarrhea, and nerve damage, limiting their use to patients with relatively preserved function,” Kim said, “And most patients still ultimately relapse and progress.”
In addition, studies show that new immuno-oncology agents, such as anti-PD-1 or anti-CTLA-4 are not effective in PDAC. This is partly because the drugs create a microenvironment that weakens the immune system and prevent cancer-fighting T-cells from entering the tumor mass.
“That’s why there is a critical unmet need to develop better therapeutic options for aggressive and refractory PDAC,” said distinguished professor of pharmaceutical sciences and chemical engineering at Northeastern University. Amiji is Northeastern’s principal investigator for the study and the scientific advisor for TargaGenix. “We are pleased to collaborate with colleagues at UC Davis and TargaGenix on this research. Based on the high mortality associated with pancreatic cancer, the opportunity for us to develop TGX-1214 for this dreadful disease is especially exciting.”
Promising TGX-1214 combination strategy for the treatment of advanced pancreatic cancer
The team will leverage the multi-disciplinary expertise of scientists and clinicians to develop an effective treatment based on the combination of TGX-1214 and immune checkpoint inhibition, which block proteins called checkpoints. Immune checkpoint inhibitors help T cells kill cancer cells better.
Previous studies indicate that TGX-1214 is safe and effective in multiple animal studies. In preliminary studies, TGX-1214 strongly inhibited pancreatic cancer growth, with complete tumor regression in two pre-clinical models of pancreatic cancer.
The long-term goal of the research is to develop safe and effective treatment strategies for PDAC to test in clinical trials that will become available for patients.
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UC Davis Comprehensive Cancer Center
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Newswise — A team of researchers at Rensselaer Polytechnic Institute led by Helen Zha, assistant professor in the Isermann Department of Chemical and Biological Engineering, has been awarded a $745,000 grant from the National Science Foundation (NSF) to explore sustainable alternatives to the synthetic textiles used in “fast fashion.”
The fashion industry is responsible for immense amounts of waste. In response to consumer demand for inexpensive clothing, manufacturers rely on textiles derived from crude oil and methane: polyesters, polyurethanes, and nylons. Many of the products are worn minimally before being disposed. The result? The clothes are incinerated or sent to landfills and because these materials never biodegrade, they remain as pollutants in the environment for hundreds of years. The fashion industry now accounts for 5-10% of all global greenhouse gas emissions, and that figure is expected to grow.
With this grant, Zha and the Rensselaer team will develop processes for manufacturing renewable fossil-free yarns, dyes, and leather-like fabrics made from fungi, plants, and artificial nature-inspired proteins. These biodegradable textiles perform as well or better than the fossil-derived materials that they will replace. The team will also develop leather alternatives using the same ingredients, since current leather manufacturing is not sustainable.
“Materials sustainability is currently one of the biggest challenges facing society,” said Zha. “While research in my lab works to address a broad range of technological challenges such as materials for enhanced drug delivery or tissue regeneration, reducing recalcitrant waste and developing new materials that are made from renewable resources are also top priorities.”
Zha will work with Daniel Walczyk, professor of mechanical, aerospace, and nuclear engineering; Johnson Samuel, associate professor of mechanical, aerospace, and nuclear engineering; Kenneth Simons, associate professor of economics; and Mattheos Koffas, Dorothy and Fred Chau ʼ71 Career Development Constellation Professor in Biocatalysis and Metabolic Engineering. Walczyk and Samuel will develop new manufacturing processes for hemp and mycelium-based materials that incorporate artificial silk protein as an additive. Simons will examine the dynamics of industrial organization and technological change. Koffas and Zha will engineer microorganisms to produce artificial silk proteins and textile dyes.
“Making sustainable materials is a big challenge,” said Shekhar Garde, Dean of the School of Engineering. “I am pleased to see that convergence of ideas from different disciplines focused on biomolecules, processes, and materials is helping address this challenge.”
“Natural spider silk is one of the most robust materials found in nature,” Zha said. “However, farming spiders is impossible due to their cannibalistic nature. Instead, we engineer bacteria to produce an artificial version. It is a commercially scalable and green manufacturing process, similar to brewing beer or making yogurt. One of our most exciting bacteria strains uses waste polyethylene as a food source to produce the recombinant spider silk protein.”
This project is one of 16 projects funded under NSF’s Convergence Accelerator program, Track I: Sustainable Materials for Global Challenges, which aims to converge advances in fundamental materials science with materials design and manufacturing methods. This program will couple end-use and full life-cycle considerations to make environmentally and economically sustainable materials and products that address global challenges.
“The Convergence Accelerator is a relatively young NSF program, but our unique program model is focused on delivering tangible solutions to address societal and economic challenges,” said Douglas Maughan, head of the NSF Convergence Accelerator program. “We are excited to have selected teams focused on developing use-inspired solutions to address complex societal and economic challenges.”
“This exceptional research team is not only innovating much-needed eco-friendly materials, but they are priming their innovations for market,” said Deepak Vashishth, Yamada Corporation Professor and Director of the Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS). “I’m looking forward to seeing the advances made possible thanks to this funding from the NSF.”
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Newswise — It’s almost Valentine’s Day, and love is in the air. Or in the waxy coating on your skin, if you are a vinegar fly. That’s where flies encounter pheromones that play an important role in regulating sexual attraction.
Flies use pheromones to ensure that they court and mate with members of the same species. As new fly species split off from a common ancestor, but continue to share the same environment, they need a way to rapidly diversify their pheromones to suppress inter-species mating. When members of two related species stop finding each other attractive, this helps prevent interbreeding.
But it’s more complicated than “she loves me, she loves me not.“
Because the perception and production of pheromones are mediated by different tissues and cellular pathways, evolving new mating pheromones requires a coordinated evolution of both the genes responsible for sensing the pheromones as well as the genes that produce them.
A new study in iScience led by Yehuda Ben-Shahar at Washington University in St. Louis identifies a link between the genetic instructions for the production and perception of sex pheromones. The research was conducted in collaboration with Jocelyn Millar from the University of California, Riverside.
Researchers reported that a single protein called Gr8a is expressed in different organs in male and female flies and appears to play an inhibitory role in mating decision-making. The findings point to one of the ways that flies could put up behavioral barriers to protect against mating with the wrong kind of partner.
“Mating pheromones often show rapid evolution,” said Ben-Shahar, a professor of biology in Arts & Sciences. “Because pheromonal communication requires a very robust and specific structural recognition of chemicals used as pheromones by the proteins that bind them in sensory neurons (chemoreceptors), it means that major molecular changes in either the receptor or the pheromone would reduce sexual attraction between males and females.”
Ben-Shahar and his team found that Gr8a was expressed in tissues in fly mouthparts, including the proboscis, as well as in taste neurons in the forelegs of both males and females. They also found Gr8a in cells in the abdomens of males. This was important because it provided Ben-Shahar and his team the first hint that a gene that had been previously identified as a sensory chemoreceptor must also have non-neuronal functions.
“Our findings provide a relatively simple molecular explanation for how signal production and perception are tied together in vinegar flies,” Ben-Shahar said. “A single pleiotropic protein can function as both a receptor for pheromones in sensory neurons, as well as contribute to their production in the pheromone-producing cells (oenocytes) of males, by way of a less-understood process.”
In one of the experiments that Ben-Shahar and his team conducted, the scientists took flies that were mutant for the Gr8a receptor and reconstituted them using input from a different vinegar fly species. This experiment showed that introducing Gr8a from another species was enough to change the overall pheromone profile of the animal.
The scientists still have not pinpointed exactly how the chemoreceptor affects the way the signal is produced, but they do know that it causes quantitative and qualitative differences in pheromones. And even small changes in pheromones could be enough to keep closely related flies from finding each other attractive — and change their mate choice behaviors.
The question of how closely related species evolve and maintain behavioral mating barriers is one that has implications for several different basic and applied biological research fields.
“Based on what we have observed, mutations in a single gene could provide a molecular path for a pheromonal communication system to evolve while still maintaining the functional coupling between a pheromone and its receptor,” Ben-Shahar said. “Our research uncovers a potential avenue for pheromonal systems to rapidly evolve when new species arise.”
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This work was supported by National Science Foundation grants 1322783, 1754264 and 1707221, and National Institutes of Health (NIH) grant NS089834.
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Newswise — CHICAGO — DePaul University and Rosalind Franklin University of Science and Medicine are funding three faculty research projects that bring together artificial intelligence, biomedical discovery and health care. The competitive grants kickstart research among interdisciplinary teams, which include biologists, computer scientists, a geographer and a physicist.
The first project will combine wearable, robotic sensors with GPS mapping to predict and prevent falls and injury among patients and members of the military. Another will analyze neurons in the brainstem to discover boundaries that control speech and swallowing. The third project uses machine learning and video tracking to develop early detection for illnesses like Parkinson’s disease.
“We are thrilled with the scope and vision of these collaborative research projects from DePaul and Rosalind Franklin faculty members,” said Salma Ghanem, provost of DePaul University. “Together, we have the potential to see artificial intelligence fuel major advances for human health in our lifetime.”
“This AI initiative and the outstanding funded first-round pilot projects represent the next step in the ongoing research collaboration between our two universities, which to date has yielded substantive outcomes,” said Ronald Kaplan, executive vice president for research at Rosalind Franklin University. “We believe this cutting-edge work has significant potential to improve health within our society.”
Wearable sensors, GPS combine to prevent injury
“We can tell a lot about a person’s health from how they walk,” said Sungsoon (Julie) Hwang, professor of geography at DePaul. She is teaming up with robotics expert Muhammad Umer Huzaifa and data scientist Ilyas Ustun. Their research will combine wearable technology and GPS to track a person’s gait.
In his robotics and AI lab, Huzaifa deploys Inertial Measurement Units (IMU) to track whether a person is walking, sitting or even falling. These sensors, which measure a body’s movement by detecting the direction of gravity and rotational speeds, may be worn as part of an exoskeleton. “Predicting harmful walking patterns and preventing falls has implications for people in a health care setting and members of the military deployed in the field,” Huzaifa explained.
DePaul faculty will work with Chris Connaboy, director of the Center for Lower Extremity Ambulatory Research at Rosalind Franklin, to use data from his lab. Ustun will use machine learning to integrate the GPS and IMU data, potentially predicting where injuries and falls could occur.
“Our movements create patterns, and we want to identify distinct patterns using machine learning to help assess an individual’s current health, especially those who are at risk,” Ustun said.
Machine learning discovery in the brainstem
The brainstem is responsible for breathing and swallowing, which can have implications for speech disorders, apnea and Sudden Infant Death Syndrome. “Within the brainstem, neurons are not clearly differentiated,” said Jacob Furst, professor of computing at DePaul. “Our project will look for genetic signatures that may differentiate the cells when there is no obvious physical difference.”
“There is so much data being generated in the life sciences that it can be difficult to look for patterns to discover key biological insights,” said Thiru Ramaraj, an assistant professor of bioinformatics at DePaul. Drawing from an atlas of existing high resolution genome wide expression data from the adult mouse brain, Ramaraj and team will employ advance machine learning to identify clusters and borders within brainstem neurons.
Working with questions that are important to brainstem researcher Kaiwen Kam at Rosalind Franklin, the team hopes to develop a neuroanatomical screening, which may also have applications for other types of tissue.
“It’s both challenging and exciting to apply computational techniques to problems that have a real impact on health,” Ramaraj said.
Diagnosing neurological disorders through AI movement patterns
Eric Landahl is a DePaul physicist who has spent much of his career making movies of molecules, including work at Argonne National Laboratory. “Hollywood movies are usually filmed at 24 frames a second, but atoms move at a speed closer to a billion frames a second,” Landahl said. His research uses x-rays and lasers and creates massive amounts of data.
He is joining EunJung Hwang at Rosalind Franklin to use a similar approach to tracking the movements of mice with Parkinson’s. Using cloud computing and machine learning, they aim to develop a model that can predict neurological disorders before they’re visible to a trained medical professional.
“This is the chance to be at the forefront of modern approaches to data analysis,” Landahl said. “This research grant gives us the chance to briefly step away from our daily work to work on something exciting that could become something bigger in the future.”
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Newswise — WASHINGTON, D.C. – Today, the U.S. Department of Energy (DOE) announced $9.1 million in funding for 13 projects in Quantum Information Science (QIS) with relevance to nuclear physics. Nuclear physics research seeks to discover, explore, and understand all forms of nuclear matter that can exist in the universe – from the subatomic structure of nucleons, to exploding stars, to the emergence of the quark-gluon plasma seconds after the Big Bang.
Quantum computers have the potential for computational breakthroughs in classically unsolvable nuclear physics problems. Quantum sensors exploit distinct quantum phenomena that do not have classical counterparts, to acquire, process, and transmit information in ways that greatly exceed existing capabilities or sensitivities.
“Although we are just beginning to develop the knowledge and technology needed to power a revolutionary paradigm shift to quantum computing, there is a clear line of sight on how to proceed,” said Tim Hallman, DOE Associate Director of Science for Nuclear Physics. “These awards will contribute to advancing nuclear physics research and to pressing future quantum computing developments forward.”
The selected projects are at the forefront of interdisciplinary research in both fundamental research and use-inspired challenges at the interface of nuclear physics and QIS technologies. Projects include advancing the development of next generation materials and architectures for high coherence superconducting quantum bits, or “qubits,” and a solid-state quantum simulator for applications in nuclear theory. Projects will also develop quantum sensors to enhance sensitivity to new physics beyond the Standard Model and improve precision measurements of nuclear decays. The quantum computing projects explore difficult nuclear physics problems using hardware advantages offered by different near-term quantum platforms.
The projects were selected by competitive peer review under the DOE Funding Opportunity Announcement for Quantum Horizons: QIS Research and Innovation for Nuclear Science.
Total funding is $9.1 million for projects lasting up to 3 years in duration. The list of projects and more information can be found here.
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Newswise — About 5.1 million people in the U.S. have a history of epilepsy, which causes repeated seizures. According to the Epilepsy Foundation, epilepsy is the fourth most common neurological disorder. While current research has shown an increase in anxiety and depression among people with epilepsy, little is known about this population and agoraphobia, an anxiety disorder that involves the fear of being in a public place or in a situation that might cause panic or embarrassment.
However, a recent study from Heidi Munger Clary, M.D., M.P.H., associate professor of neurology at Wake Forest University School of Medicine, shows that phobic and agoraphobic symptoms are common and associated with poor quality of life in people with epilepsy.
The study appears online in Epilepsy Research.
“We know that agoraphobia can lead to delays in patient care because of a reluctance to go out in public, which includes appointments with health care providers,” said Munger Clary, the study’s principal investigator. “So, this is an area that needs more attention in clinical practice.”
In the study, researchers conducted a cross-sectional analysis of baseline clinical data from a neuropsychology registry cohort study. Researchers analyzed a diverse sample of 420 adults, ages 18 to 75, with epilepsy who underwent neuropsychological evaluation over a 14-year period at Columbia University Medical Center in New York.
“More than one-third of the participants reported significant phobic/agoraphobic symptoms,” Munger Clary said. “We also found that phobic/agoraphobic symptoms, along with depression symptoms, were independently associated with poor quality of life, but generalized anxiety symptoms were not.”
According to Munger Clary, because phobic/agoraphobic symptoms are not routinely assessed by clinicians, the findings may suggest a need for future studies to develop more comprehensive screeners for psychiatric comorbidity in epilepsy.
“Symptoms of agoraphobia do not fully overlap with generalized anxiety or depression symptoms that are often screened in routine practice,” Munger Clary said. “Providers might want to consider more robust symptom screening methods to identify and better assist these patients. This may be important to improve health equity, given other key study findings that show those with lower education and non-white race/ethnicity had increased odds of significant phobic/agoraphobic symptoms.”
This work was supported in part by the National Institutes of Health under grants R01 NS035140, KM1 CA156709, UL1 TR001420 and 5KL2TR001421-04.
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Newswise — WASHINGTON, D.C. – Today, the U.S. Department of Energy (DOE) announced $105 million for research in biopreparedness. This funding, provided by the Office of Science, will support fundamental research to accelerate breakthroughs in support of the Biopreparedness Research Virtual Environment (BRaVE) initiative.
“BRaVE will take advantage of DOE’s unique capabilities and facilities in physical, computational, and life sciences to support our nation’s biopreparedness and response to future pandemics and other biological threats,” said Asmeret Asefaw Berhe, DOE’s Director of the Office of Science. “The knowledge and capabilities advanced by this research will have broader impacts in energy, climate change, food security, health, sustainability, and other areas critical to national and economic security.”
During the COVID crisis, DOE’s national laboratory researchers provided epidemiological information to decision makers, assessed and developed new virus testing protocols, identified high potential candidates for antiviral drugs and delivered manufacturing solutions to stem the shortages of face masks, test kits, and other supplies. In addition, DOE’s user facilities supported researchers in the fight against COVID-19, including providing X-ray structural information that supported the development of all three vaccines approved in the U.S., as well as FDA-approved antiviral drugs and antibodies.
BRaVE will build upon these high impact results to provide the underpinning science to enable DOE’s strategy for biopreparedness and response by focusing on five focus areas.
Applications are open to the DOE national laboratories. Partnerships with other institutions, including academia, other national laboratories, not-for-profit organizations, or industry, are strongly encouraged. To strengthen the commitment to promoting a diversity of investigators and institutions supported by the DOE Office of Science, applications are explicitly encouraged that involve Minority Serving Institutions (MSIs), including Historically Black Colleges and Universities (HBCUs).
Total combined planned funding is up to $105 million over three years, with $35 million in Fiscal Year 2023 dollars and outyear funding contingent on congressional appropriations. The funding anticipated for each award is $2M to $4M per year.
The program announcement, sponsored by the Offices of Advanced Scientific Research Computing, Basic Energy Sciences, and Biological and Environmental Research within the Department’s Office of Science, can be found here.
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Newswise — Tissue transparency—a useful skill for animals that want to hide from predators—is common in aquatic environments, but is extremely rare on land. One exception is the glassfrog, so named because its internal organs can be seen through its transparent skin and muscles. This frog is active at night and spends its days sleeping on leaves, becoming nearly invisible on the foliage. But how exactly this creature makes itself transparent has been somewhat of a mystery.
Using state-of-the-art imaging technology, NIH-funded researchers have found the secret behind the glassfrog’s camouflage. Their findings, recently published on the cover of Science, demonstrate that glassfrogs can remove almost 90% of their red blood cells from circulation, storing them in the liver during rest. This mechanism, along with its inherently see-through tissues, allows the glassfrog to increase its transparency by two- to threefold, seemingly on demand.
“In vertebrates like humans, tissue transparency is particularly difficult to achieve, as our circulatory systems are filled with oxygen-carrying red blood cells that strongly absorb light and render our tissues opaque,” explained NIBIB-funded researcher Junjie Yao, Ph.D., an assistant professor of biomedical engineering at Duke University. “In our study, we have discovered that the glassfrog can conceal nearly all of its red blood cells within its liver on a daily basis, resulting in a unique form of camouflage that is distinct from all other known mechanisms of tissue transparency. Understanding this blood flow mechanism in the glassfrog may provide insights into disorders related to blood clotting or stroke in humans.”
The glassfrog’s camouflage is adaptive—the creature has peak transparency when it is asleep and at increased risk of attack. To understand the mechanism of this transparency, the researchers first used spectroscopy techniques to passively measure glassfrog’s levels of hemoglobin (a protein in red blood cells that carries oxygen and absorbs light). They found that hemoglobin levels were barely distinguishable when the frogs were sleeping, but markedly increased after exercise. This means that the glassfrog depletes its red blood cells from circulation during rest, allowing for enhanced tissue transparency and camouflage during this vulnerable time.
But where exactly are these red blood cells going while the glassfrog is asleep? To answer this question, the researchers used an advanced technique called photoacoustic microscopy, a hybrid imaging method that takes advantage of both light and sound waves. Here’s how it works: When a tissue absorbs light, some of that absorbed energy is converted into ultrasound waves. Measuring these ultrasound waves with a specialized transducer can give detailed information about molecules and tissues under the skin’s surface. In this study, the researchers optimized this technique so that they could detect light absorbed by hemoglobin—this way, the resulting ultrasound waves would give information about glassfrogs’ red blood cell movement.
“Photoacoustic microscopy allowed us to capture the blood flow dynamics of the glassfrogs, even though those changes occur deep inside their opaque internal organs,” explained Carlos Taboada, Ph.D., a postdoctoral associate at Duke University and one of the leading authors of this study. “This aspect of the technique was really important, because many internal organs of the glassfrog contain millions of nanocrystals that attenuate most incident light. Traditional imaging methods can’t track blood flow with such a high level of accuracy or tell us exactly where the glassfrogs are storing their red blood cells.”
Using photoacoustic microscopy, the researchers imaged the glassfrogs while under anesthesia (which leads to red blood cells being distributed throughout the entire body), while sleeping, and after exercise. During rest, the researchers found that the glassfrogs’ circulating pool of red blood cells decreased by 80-90%, with the hemoglobin signal concentrated in the liver. Imaging the frogs after exercise revealed that the blood flows out of the liver and back into circulation during activity, with the red blood cells reaggregating in the liver within roughly an hour after movement.
By revealing the mechanism of the glassfrog’s camouflage, a new question has surfaced: How do these creatures concentrate most of their red blood cells in their liver without triggering clotting events? “At this point, we really know very little about this important physiological function in glassfrogs, but we are actively working to understand this phenomenon, which has significant clinical implications,” said Yao. “This anti-clotting mechanism is highly relevant for treating thrombosis and stroke, as well as improving medical interventions that require removing blood from the body (like dialysis), where blood clotting is a major concern.”
Future work in this space can take advantage of the unique ability of photoacoustic imaging to track glassfrog’s blood flow—in a safe and unobtrusive way that does not disturb the animals. “By optimizing photoacoustic imaging to specifically detect hemoglobin, the researchers were able to observe the glassfrogs’ natural blood flow dynamics without injecting contrast agents, representing a truly non-invasive approach,” said Randy King, Ph.D., a program director in the Division of Applied Science & Technology at NIBIB. “What’s more, this study highlights how photoacoustic microscopy can be tailored to investigate different aspects of blood dynamics, providing both high-resolution and real-time information.”
This study was supported by grants from NIBIB (R01EB028143), the National Institute of Neurological Disorders and Stroke (NINDS; R01NS111039), and the NIH BRAIN Initiative (RF1NS115581).
This Science Highlight describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process—each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
Study reference: Carlos Taboada et al. Glassfrogs conceal blood in their liver to maintain transparency. Science (2022). DOI: 10.1126/science.abl6620
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Newswise — WINSTON-SALEM, N.C. – Jan. 9, 2023 – Food insecurity, which is the limited or uncertain availability of nutritionally adequate and safe food, impacts about 10.2% of U.S. households, according to the U.S. Department of Agriculture Economic Research Service. In families with children in the home, food insecurity is even higher, at 12.5%.
Previous studies have shown an association between food insecurity and individual health care expenditures, but there is little research on how food insecurity impacts families’ health care use.
Now, researchers at Wake Forest University School of Medicine are reporting the results of a new study that shows food-insecure families have higher health care expenditures than families that are food secure.
The study was released today in the January issue of Health Affairs.
“We know that food insecurity has a negative impact on individual health outcomes,” said Deepak Palakshappa, M.D., associate professor of general internal medicine at Wake Forest University School of Medicine and principal investigator of the study. “But we need a better understanding of the financial implications on families and health care expenditures.”
In the retrospective study, Palakshappa’s team sought to determine the association between a family’s food insecurity over the course of one year and their health care expenditures throughout the following year. Researchers analyzed data from the 2016 and 2017 Medical Expenditure Panel Survey, a large-scale survey conducted annually by the Agency for Healthcare Research and Quality that is representative of the U.S. population. The survey collects information from U.S. medical providers about health care services, health insurance, expenditures and sociodemographic characteristics.
The team collected data on 14,666 individuals from 6,621 families and found that food-insecure families had 20% greater total health care expenditures than food-secure families, an annual difference of about $2,456.
“We found that food insecurity in 2016 was associated with increased care expenditures in 2017 among families regardless of insurance coverage type,” Palakshappa said.
The results also have significant implications for any potential programs or policies aimed at addressing food insecurity.
“Interventions that address food insecurity in one or more specific family members may also provide benefits to others in the home,” Palakshappa said. “And there’s a potential financial benefit for insurers to invest in these programs.”
Palakshappa’s team also found that 1 in 5 families had more than one insurance plan, making it challenging to determine the full financial benefit of food insecurity interventions in households with mixed insurance coverage.
“More parents are enrolling their children in Medicaid or CHIP instead of their employer-sponsored health insurance because of increased out-of-pocket expenses,” Palakshappa said. “However, the expansion of public subsidies such as the Supplemental Nutrition Assistance Program or child tax credits can alleviate food insecurity.”
Palakshappa said additional research is needed to evaluate how addressing food insecurity at an individual patient visit may affect the health outcomes and health care utilization of other family members.
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Newswise — A pair of Clemson University researchers are collaborating to discover why fungal pathogens become drug resistant.
Genetics and Biochemistry Associate Professor Lukasz Kozubowski and Chemistry Professor Julia Brumaghim are studying how the fungal pathogen Cryptococcus neoformans develops resistance to azole compounds, a class of fungicides that are widely used in agriculture for crop protection and as a treatment for life-threatening human fungal infections. They received a $492,000 National Science Foundation grant for the work.
Only three types of antifungal drugs exist, so drug resistance can severely limit treatment options.
Most azole compounds work by inhibiting fungi rather than killing them, which makes the drugs safer for humans, said Kozubowski, co-principal investigator on the project. That’s because both humans and fungi are eukaryotic. Therefore, drugs designed to kill fungi may also harm their human hosts. Eukaryotes are single-celled or multicellular organisms whose cells contain a distinct, membrane-bound nucleus.
Conversely, while fungi-inhibiting drugs are safer for humans, their use also increases the chance of drug resistance.
“We know resistance to azoles is a fact,” Kozubowski explained. “Apparently, the drugs can somehow stimulate the development of resistance. It is counterintuitive: You may think of a drug as killing or inhibiting the pathogen, but the drugs have some propensity to stimulate the development of resistance to the same drugs. So what they are supposed to kill, the drugs are actually stimulating the cells to develop a resistance to it.”
It’s rare that a fungal cell isn’t killed or inhibited by antifungal treatment — and that adds a complication for the scientists.
“The problem with resistance is that it’s quite an elusive target when it comes to understanding because essentially what we are after is an event that happens maybe one in a million times,” Kozubowski said. “You have a population of millions of cells, and unfortunately, if the drug doesn’t kill them all, there will always be that lucky cell, that one in a million, that develops something that causes resistance.”
Drug resistance is also a problem with antibiotics, Kozubowski noted.
Fungal drug resistance is an emerging problem that is also growing in scope, adding to the urgency of the Clemson scientists’ work. “It’s not a last-year emerging, but in the past decades, we’ve been experiencing drug-resistant fungal infections. That’s true for bacterial infections as well,” Kozubowski said.
Ultimately, he said the researchers’ goal is to better understand how drugs such as the azole compounds stimulate the mechanism of drug resistance. A top suspect: damaged DNA.
Enter Brumaghim, the project’s principal investigator, who said she became interested in the project because her work focuses on how cellular DNA becomes damaged, which complements Kozubowski’s research.
“I got involved in the project because I found out [Kozubowski] was working on how these compounds generate reactive oxygen species like the radical species that can damage DNA,” Brumaghim recalled.
Reactive oxygen species are unstable molecules that contain oxygen and easily react with other molecules in a cell.
“He said, ‘this is the mechanism, but we know nothing about how this could happen.’ And that’s what I do. We look at how metals generate these radical species that damage DNA,” Brumaghim said
Then, the question facing Brumaghim and Kozubowski was, “what happens if you have more damage [to cellular DNA] than can be repaired,” Brumaghim said. “Then you get into trouble. If a cell cannot replicate its DNA sufficiently, it will die. It’s called ‘programmed cell death.’… The alternative to that is when you have mutations to the DNA, and the cell would be better off dying, but it doesn’t — that leads to cancer. Or with fungi, it leads to drug resistance — or that’s what we think.”Kozubowski described the interdepartmental collaboration as a “natural match.”
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Newswise — BLOOMINGTON, Ind. — The length of a specific generation can tell us a lot about the biology and social organization of humans. Now, researchers at Indiana University can determine the average age that women and men had children throughout human evolutionary history with a new method they developed using DNA mutations.
The researchers said this work can help us understand the environmental challenges experienced by our ancestors and may also help us in predicting the effects of future environmental change on human societies.
“Through our research on modern humans, we noticed that we could predict the age at which people had children from the types of DNA mutations they left to their children,” said study co-author Matthew Hahn, Distinguished Professor of biology in the College of Arts and Sciences and of computer science in the Luddy School of Informatics, Computing and Engineering at IU Bloomington. “We then applied this model to our human ancestors to determine what age our ancestors procreated.”
According to the study, published today in Science Advances and co-authored by IU post-doctoral researcher Richard Wang, the average age that humans had children throughout the past 250,000 years is 26.9. Furthermore, fathers were consistently older, at 30.7 years on average, than mothers, at 23.2 years on average, but the age gap has shrunk in the past 5,000 years, with the study’s most recent estimates of maternal age averaging 26.4 years. The shrinking gap seems to largely be due to mothers having children at older ages.
Other than the recent uptick in maternal age at childbirth, the researchers found that parental age has not increased steadily from the past and may have dipped around 10,000 years ago because of population growth coinciding with the rise of civilization.
“These mutations from the past accumulate with every generation and exist in humans today,” Wang said. “We can now identify these mutations, see how they differ between male and female parents, and how they change as a function of parental age.”
Children’s DNA inherited from their parents contains roughly 25 to 75 new mutations, which allows scientists to compare the parents and offspring, and then to classify the kind of mutation that occurred. When looking at mutations in thousands of children, IU researchers noticed a pattern: The kinds of mutations that children get depend on the ages of the mother and the father.
Previous genetic approaches to determining historical generation times relied on the compounding effects of either recombination or mutation of modern human DNA sequence divergence from ancient samples. But the results were averaged across both males and females and across the past 40,000 to 45,000 years.
Hahn, Wang and their co-authors built a model that uses de novo mutations — a genetic alteration that is present for the first time in one family member as a result of a variant or mutation in a germ cell of one of the parents or that arises in the fertilized egg during early embryogenesis — to separately estimate the male and female generation times at many different points throughout the past 250,000 years.
The researchers were not originally seeking to understand the relationship of gender and age at conception over time; they were conducting a broader investigation about the number of mutations passed from parents to children. They only noticed the age-based mutation patterns while seeking to understand differences and similarities between these pattens in humans versus other mammals, such as cats, bears and macaques.
“The story of human history is pieced together from a diverse set of sources: written records, archaeological findings, fossils, etc.,” Wang said. “Our genomes, the DNA found in every one of our cells, offer a kind of manuscript of human evolutionary history. The findings from our genetic analysis confirm some things we knew from other sources (such as the recent rise in parental age), but also offer a richer understanding of the demography of ancient humans. These findings contribute to a better understanding of our shared history.”
Additional contributors to this research were Samer I. Al-Saffar, a graduate student at IU at the time of the study, and Jeffrey Rogers of the Baylor College of Medicine.
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Indiana University
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Newswise — Eukaryotic cells — the ones that make up most life as we know it, including all animals, plants and fungi — are highly structured objects.
These cells assemble and maintain their own smaller, internal bits: the membrane-bound organelles like nuclei, which store genetic information, or mitochondria, which produce chemical energy. But much remains to be learned about how they organize themselves into these spatial compartments.
Physicists at Washington University in St. Louis conducted new experiments that show that eukaryotic cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship that the scientists predict theoretically, their new framework suggests that organelles grow in random bursts from a limiting pool of building blocks.
The study was published Jan. 6 in Physical Review Letters.
“In our work, we suggest that the steps by which organelles are grown — far from being an orderly ‘brick-by-brick’ assembly — occur in stochastic bursts,” said Shankar Mukherji, assistant professor of physics in Arts & Sciences.
“Such bursts fundamentally limit the precision with which organelle size is controlled but also maintain noise in organelle size within a narrow window,” Mukherji said. “Burstlike growth provides a general biophysical mechanism by which cells can maintain, on average, reliable yet plastic organelle sizes.”
Organelles must be flexible enough to allow cells to grow or shrink them as environments demand. Still, the size of organelles must be maintained within certain limits. Biologists have previously identified certain molecular factors that regulate organelle sizes, but this study provides new insights into the quantitative principles underlying organelle size control.
While this study used budding yeast as a model organism, the team is excited to explore how these assembly mechanisms are utilized across different species and cell types. Mukherji said that they plan to examine what these patterns of robustness can teach us about how to harness organelle assembly for bioengineering applications and how to spot defects in organelle biogenesis in the context of disease.
“The pattern of organelle size robustness is shared between budding yeast and human iPS cells,” Mukherji said. “The underlying molecular mechanisms producing these bursts are yet to be fully elucidated and are likely to be organelle-specific and potentially species-specific.”
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Amiri KP, Kalish A and Mukherji S. Robustness and Universality in Organelle Size Control. Phys. Rev. Lett., Jan. 7, 2023. https://link.aps.org/doi/10.1103/PhysRevLett.130.018401
Funding: This research was supported by the National Institutes of Health (NIH R35GM142704).
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Newswise — DETROIT – A Wayne State University researcher has received a $1.7 million, five-year award from the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health for the study, “Targeting nitrative stress for treatment of cisplatin ototoxicity.” The research aims to address the critical gap that exists in understanding how nitrative stress caused by cisplatin treatment alters cochlear protein signaling causing apoptosis – or death of cells – in cisplatin-induced ototoxicity.
The study, led by Samson Jamesdaniel, Ph.D., assistant professor of family medicine and public health in Wayne State’s School of Medicine and in the Institute of Environmental Health Sciences, stated that cisplatin and its analogs are prescribed to 10 to 20% of all cancer patients, causing hearing loss in up to 80% treated with the drug.
“Cisplatin is a first-generation platinum-based anti-neoplastic drug that is the backbone of combination therapies to treat cancers of the bladder, cervix, lung [non-small cell], head and neck [squamous cell], testicle, mesothelium and some other solid tumors,” said Jamesdaniel. “The ototoxicity caused by treatments using cisplatin can significantly affect the quality of life in cancer survivors and lead to devastating consequences in children, with impacts on speech and language development, education and social integration.”
Cisplatin-induced nitration and downregulation of LMO4, a molecular adaptor protein, appears to mediate its ototoxic effects. Jamesdaniel and his research team hope to better understand the characterization of the regulatory role of LMO4 nitration in cisplatin-mediated ototoxicity that may reveal the biological significance of this novel molecular mechanism.
“The outcomes of this research will have important translational value by providing a strong foundation for identifying and developing novel therapeutic approaches to prevent the ototoxic effects of cisplatin,” said Timothy Stemmler, Ph.D., interim vice president for research at Wayne State. “Samson’s important research may lead to an effective intervention for cisplatin-induced ototoxicity that will improve lives of cancer survivors who have received this treatment.”
The project number for this National Institutes of Health study is DC020299. To learn more, visit https://reporter.nih.gov/search/BwG81rDmTEKfb7HqEjgC-g/project-details/10587579
About Wayne State University
Wayne State University is one of the nation’s pre-eminent public research universities in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit research.wayne.edu.
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Newswise — PHILADELPHIA— Penn Medicine has received a $9.7 million grant from The Warren Alpert Foundation (WAF) that will fund continuing education efforts for genetic counselors, to ensure opportunities for continued training that will keep them on the leading edge of their profession interpreting genomic data and explaining its implications to patients. This grant will position genetic counselors to advance research to address the many critical questions in the implementation of genomic information into clinical practice.
Spearheaded by genetics researchers and faculty members in the Perelman School of Medicine (PSOM) at the University of Pennsylvania, the WAF-Career Ladder Education Program for Genetic Counseling program will allow genetic counselors to continue their education and learn about new and emerging research trends. This advanced training will further inform their work helping individuals learn about specific hereditary disorders, assess risks, and make proactive decisions in areas from cancer prevention to family planning. Penn will lead these efforts, in close collaboration with four other leading institutions: Baylor College of Medicine, Northwestern University Feinberg School of Medicine, Vanderbilt University School of Medicine, and the University of Washington School of Medicine.
According to the U.S. Bureau of Labor Statistic, the genetics counseling field is expected to see rapid growth over the next decade. To enter the field, genetic counselors typically must complete a bachelors degree and a masters degree related to the field. However, unlike other health professions, there are currently few opportunities to formally continue and advance their training with this career. “Genetic counseling is only about 50 years old, and the world of genetics is moving at lightning speed. It can be challenging for genetic counselors to stay aware of the rapid changes in the field—especially for those based at smaller, community hospitals. It is vital for the field to keep genetic counselors on the forefront of research and education, and initiatives like this help to ensure genetic counselors are an integral part of the future of genomic medicine,” said Kathleen Valverde, PhD, LCGC, director of Penn’s Master of Science in Genetic Counseling Program.
The grant funds the newly created WAF-Career Ladder Education Program for Genetic Counseling at Penn, which aims to drive continued education for genetic counselors through multiple pathways. This includes the creation of a state-of-the-art online continuing education unit (CEU) courses for genetic counselors. Each one-credit CEU course will contain 10 hours of instruction, lectures, activities, and assessments to provide in-depth coverage on designated topics in genomics and personalized medicine such as variant interpretation. Other initiatives include developing a certificate program with targeted area of advanced training, and pathways for the development of a post-graduate doctoral degree in genetic counseling, are being explored.
“Genetic counselors are crucial for all aspects of genomic medicine, including molecular diagnostics, clinical genetics, and genomics research, and are essential to modern health care systems. Creating a robust career ladder to support genetic counselors’ advanced training and professional development is critical in retaining genetic counselors in academic health systems, advancing genomics research, and implementing genomic information into clinical practice,” said Daniel Rader, MD, chair of Genetics and Chief of Translational Medicine and Human Genetics at Penn. “This commitment to the career development of genetic counselors will be transformational, not just at the five participating institutions but also nationally and globally.”
PSOM will partner with four other institutions around the nation: Baylor College of Medicine, Northwestern University Feinberg School of Medicine, Vanderbilt University School of Medicine, and the University of Washington School of Medicine. These institutions, along with Penn, represent geographically diverse areas of the United States, and were chosen as recipients of a portion of the WAF grant money based on their clinical programs in genetics and genomics expertise, their existing genetic counseling masters programs, and their history of engaging in research. The five institutions will work together to create and offer programs and opportunities for genetic counselors to advance their skills.
“Given the increasing complexity of career development and the expanded roles for genetic counselors, support in career development is imperative. We are excited to support the career ladder for genetic counselors and we are delighted to award Penn this grant,” said August Schiesser, WAF executive director.
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