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Fields of breeders’ dreams: A team effort toward targeted crop improvements

Community effort yields reference switchgrass genome, environmental adaptations dataCredit: David Lowry Gardeners and farmers around the country recognize that crop

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Community effort yields reference switchgrass genome, environmental adaptations data

Gardeners and farmers around the country recognize that crop varieties grow best in certain regions. Most plant species have adapted to their local environments; for example, crop and ornamental seeds sold for the upper Midwest are often very different than those bred for Texas. Identifying and breeding varieties that have high productivity across a range of environments is becoming increasingly important for food, fuel and other applications, and breeders aren’t interested in waiting decades to develop new crops.

One example is an ongoing collaborative effort to improve the emerging bioenergy crop switchgrass (Panicum virgatum), which has established 10 experimental gardens located in eight states spread across 1,100 miles. Switchgrass is a perennial grass that quickly grows in a variety of soils and water conditions, standing taller than basketball star LeBron James. In each garden, switchgrass plants clonally propagated from cuttings represent a diverse collection sourced from half of the United States.

As reported January 27, 2021 in Nature, the team led by researchers at the University of Texas (UT) at Austin, the HudsonAlpha Institute for Biotechnology (HudsonAlpha), and the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), has produced a high-quality reference sequence of the complex switchgrass genome using samples collected at these gardens. Building off this work, researchers at all four DOE Bioenergy Research Centers (BRCs)–the Great Lakes Bioenergy Research Center (GLBRC), the Center for Bioenergy Innovation, the Center for Advanced Bioenergy & Bioproducts Institute, and the Joint BioEnergy Institute–have expanded the network of common gardens and are exploring improvements to switchgrass through more targeted genome editing techniques to customize the crop for additional end products.

The genetic diversity within this set of plants, each with a fully-sequenced genome, and these gardens allow researchers to test what genes affect the plant’s adaptability to various environmental conditions. “To accelerate breeding for bioenergy, we need to make connections between the plant’s traits and genetic diversity,” said John Lovell, an evolutionary biologist at HudsonAlpha and first author of the study. “For that, it’s necessary to have the plant’s genome as a reference. Additionally, having the gardens as a resource helps breeders find genetic regions of interest.” The combination of field data and genetic information has allowed the research team to associate climate adaptations with switchgrass biology, information that could be useful toward the DOE’s interest in harnessing the crop as a versatile candidate biomass feedstock for producing sustainable alternative fuels.

Common Gardens Are A Community Effort

The common gardens began nearly a decade ago with a proposal from UT-Austin’s Tom Juenger, a longtime JGI collaborator and a senior author on this study. The use of switchgrass as a feedstock for biomass-based fuels was initially fostered by DOE’s Bioenergy Research Centers, which initiated the sequencing of the switchgrass genome. DOE’s Billion Ton Report, identified potential switchgrass production areas across the U.S., guiding the location of the common gardens. “Gardeners and farmers fully understand that when you move plants outside of their native habitat or cold hardiness zones, they have different levels of performance,” Juenger said. “The novelty here is that we’re trying to actually figure out what’s causing those differences rather than just observing them. Can we quantify them? Can we tie them to the genome? We can use common garden plantings of clonally propagated plants to address these questions.”

Multiple collection methods were applied to gather the diversity of switchgrass plants represented in the gardens. “Tom gave me a truck and I drove all over Texas with a shovel,” recalled study co-author David Lowry, who started as a postdoctoral fellow in the Juenger lab and continues to work on the project from a lab at Michigan State University that is affiliated with the GLBRC. Additional samples came from U.S. Department of Agriculture stock centers, collaborators, and collections at other field sites. “This paper is a combination of really cutting-edge genomics and genetic analysis with large scale data collection,” he added.

Jeremy Schmutz, head of the JGI Plant Program, drew parallels between these common gardens and those previously grown for the DOE candidate feedstock poplar. “You’re collecting natural diversity and you’re planting natural diversity in multiple locations, and then you are extracting links between the genetic variation and phenotypic performance,” he said. Both switchgrass and poplar are JGI Flagship Plants.

Reaping Long-Term Investment Benefits

Switchgrass has a large polyploid genome, which means most genes are found as multiple copies across the chromosomes. “In the past, we needed model systems to test genetic hypotheses in species with large and complex genomes,” said Lovell. “However, new sequencing technologies have allowed us to build the necessary genome resources to directly test for genes involved in biomass yield and climate adaptation in switchgrass, despite its physical size and genome complexity.”

Work on the switchgrass genome sequence started more than a decade ago. As sequencing technologies have advanced, assembly and annotation of the genome sequence has improved in parallel. For example, the current version of the genome is assembled into sequences of 5.5 million basepair (bp) in length, while the previous version had an average of 25,000 bp pieces. That’s the difference between assembling a 10,000-piece puzzle and doing the same puzzle with just 50 pieces.

The combination of new genetic tools and experimental gardens allow researchers to detect climate-gene matches, which can be exploited for accelerated crop improvement. “Because of the DOE’s long-term investment and the effort that has gone into this, people are going to be able to model further research on this complex species and also at the same time, take advantage of what we can do now with genomics to really make inroads into plant biology and improvements of switchgrass as the crop species,” Schmutz said.

The switchgrass genotypes that were planted into the common gardens were sequenced and assembled by the JGI, allowing the research team to conduct association mapping, linking genes to traits. One of the team’s findings is that the performance of switchgrass across the garden sites depended on the origin or collection location of the individual switchgrass plants. They were able to identify many regions in the switchgrass genome that are associated with genetic differences that lead to productivity in different environments.

For example, many plants collected from native habitats in Texas and other southern locales did not survive the cold winter of 2019 at the most northern common garden in South Dakota. Conversely, upper Midwest native switchgrass plants performed poorly at the southern common gardens in Texas. This reciprocal home site advantage is direct evidence of climatic adaptation. The team’s database of genes that underlie adaptation to climate provides breeders with a strong foundation to improve crop productivity under specific climates.

Sourcing plants from so many parts of the country also helped the team understand why some switchgrass plants from the Northeast have traits similar to those from the Midwest, even though their genomes were very different.

The high quality reference genome sequence of switchgrass is available on the JGI plant data portal Phytozome. This version can help breeders identify genomic regions of interest and directly introduce these features into new crop varieties. “It’s going to be important to have all this information in order to facilitate breeding going forward,” noted Lowry.

The team has received additional DOE funding to continue maintaining the gardens, which excites Juenger. “There will be a continuation of collecting data and information from these existing plantings, and then trying to leverage these discoveries to better understand how plants tolerate stresses and challenges in the natural environment,” he said. “There aren’t many efforts that have been able to study native perennial plants with these genetic and genomic resources, interweaved with this long longitudinal study perspective. Although it’s been this enormous investment to set up these gardens, we have them to study for a number of years. And that’s a real benefit for the research program.”

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Researchers from the University of California (UC), Berkeley, Rutgers University, USDA-ARS, Arizona Genomics Institute, University of Georgia, Athens, Clemson University, Marshall University, Jawaharlal Nehru University (India), Noble Research Institute, University of Nebraska, Lincoln, South Dakota State University, University of Missouri, Argonne National Laboratory, USDA-NRCS, Texas A&M University, UC Davis, Oklahoma State University, University of Oklahoma, and Washington State University were also involved in this work.

Publication: Lovell J et al. Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass. Nature. 2021 Jan 27. doi: 10.1038/s41586-020-03127-1.

The U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, is committed to advancing genomics in support of DOE missions related to clean energy generation and environmental characterization and cleanup. JGI provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Follow @jgi on Twitter.

DOE’s Office of Science is the 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 science.energy.gov.

Fields of Breeders’ Dreams: A Team Effort Toward Targeted Crop Improvements

As reported January 27, 2021 in Nature, the team led by researchers at the University of Texas (UT) at Austin, the HudsonAlpha Institute for Biotechnology (HudsonAlpha), and the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), has produced a high-quality reference sequence of the complex switchgrass genome using samples collected at these gardens. Building off this work, researchers at all four DOE Bioenergy Research Centers (BRCs)–the Great Lakes Bioenergy Research Center (GLBRC), the Center for Bioenergy Innovation, the Center for Advanced Bioenergy & Bioproducts Institute, and the Joint BioEnergy Institute–have expanded the network of common gardens and are exploring improvements to switchgrass through more targeted genome editing techniques to customize the crop for additional end products.

Source: https://bioengineer.org/fields-of-breeders-dreams-a-team-effort-toward-targeted-crop-improvements/

fields-of-breeders’-dreams:-a-team-effort-toward-targeted-crop-improvements

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Trial of existing antibiotic for treating Staphylococcus aureus Bacteremia begins

NIH-supported trial will test Dalbavancin in hospitalized adultsCredit: NIAID A clinical trial to test the antibiotic dalbavancin for safety and

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A clinical trial to test the antibiotic dalbavancin for safety and efficacy in treating complicated Staphylococcus aureus (S. aureus) bacteremia has begun. The trial will enroll 200 adults hospitalized with complicated S. aureus infection at approximately 20 trial sites around the United States. The trial is being sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

S. aureus is a leading cause of antibiotic-resistant infection. S. aureus infections led to nearly 20,000 deaths in 2017 in the United States, according to the U.S. Centers for Disease Control and Prevention (CDC). This bacterium is of particular concern in healthcare-associated infections. S. aureus bacteremia–an infection of the blood–often requires inserting a central intravenous (IV) catheter to deliver long courses of antibiotics, an invasive procedure that can involve long-term care in healthcare facilities.

“As antibiotic-resistant infections become more widespread, better and easier treatment regimens are needed to ease the burden on both healthcare providers and patients,” said NIAID Director Anthony S. Fauci, M.D. “By investigating existing antibiotics for their action on a broader array of bacterial infections, we may be able to generate new treatment regimens more efficiently.”

The antibiotic dalbavancin has strong activity against gram-positive bacteria, including methicillin-resistant S. aureus, which suggests it could be an effective treatment for S. aureus bacteremia. Dalbavancin is currently FDA-approved in the United States for treating acute bacterial skin and skin structure infections, including those caused by S. aureus. If the two-dose regimen being tested in this trial proves effective, it could lead to a shorter, less invasive treatment for S. aureus bacteremia that does not require an indwelling IV access for daily therapy.

The Phase 2b trial is being conducted by the NIAID-funded Antibacterial Resistance Leadership Group (ARLG) under the leadership of Thomas Holland, M.D., of Duke University (Durham, North Carolina.) It is called the “Dalbavancin as an Option for Treatment of S. aureus Bacteremia (DOTS)” trial. Patients who have stabilized after initial treatment of their bacteremia will be eligible for enrollment in this study.

“Dalbavancin is appealing as a potential option for treatment of these serious S. aureus infections, and we need high quality data to find out if it works,” said Dr. Holland, “This trial will provide clinicians and patients with that data.”

One hundred participants will be randomized to receive the standard of care for complicated infections, including appropriate antibiotics, and 100 participants will receive two doses of dalbavancin intravenously. The doses will be given one week apart. Most participants receiving dalbavancin will be given 1500 milligrams (mg) per dose. Participants with signs of kidney dysfunction will be given 1125 mg per dose. All participants will be followed for approximately 70 days after enrollment, and up to six months if they have vertebral osteomyelitis, an infection of the vertebrae.

At the end of the trial, multiple patient outcomes will be assessed: survival; additional complications (such as relapse) or clinical failures; drug-related adverse events; and overall quality of life. The therapeutic regimen will have met the primary endpoint of the trial if participants who received dalbavancin fare better on these metrics than those who received the current standard of care. This trial could validate a dalbavancin regimen of only one dose a week for two weeks, compared to daily doses administered intravenously for four to six weeks with the current standard of care.

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The ARLG is a clinical research consortium working to reduce the impact of antimicrobial resistance. It is funded through NIH grant UM1AI104681. For more information about this trial, visit ClinicalTrials.gov and search identifiers NCT04775953.

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NIAID conducts and supports research–at NIH, throughout the United States, and worldwide–to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH…Turning Discovery Into Health®

Source: https://bioengineer.org/trial-of-existing-antibiotic-for-treating-staphylococcus-aureus-bacteremia-begins/

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Metabolite fumarate can reveal cell damage: New method to generate fumarate for MRI

Researchers find new technique for rapid hyperpolarization and purification of fumarate in aqueous solution; obstacles involving the use of parahydrogen

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Researchers find new technique for rapid hyperpolarization and purification of fumarate in aqueous solution; obstacles involving the use of parahydrogen overcome

A promising new concept published by an interdisciplinary research team in “Proceedings of the National Academy of Sciences” (PNAS) paves the way for major advances in the field of magnetic resonance imaging (MRI). Their new technique could significantly simplify hyperpolarized MRI, which developed around 20 years ago for observing metabolic processes in the body. The proposal involves the hyperpolarization of the metabolic product fumarate using parahydrogen and the subsequent purification of the metabolite. “This technique would not only be simpler, but also much cheaper than the previous procedure,” said leader of the project Dr. James Eills, a member of the research team of Professor Dmitry Budker at Johannes Gutenberg University Mainz (JGU) and the Helmholtz Institute Mainz (HIM). Also participating in the project were scientists from the fields of chemistry, biotechnology, and physics at TU Darmstadt, TU Kaiserslautern, the University of California Berkeley in the United States, the University of Turin in Italy, and the University of Southampton in England.

Fumarate is a key biosensor for hyperpolarized imaging

The potential applications of MRI are hindered by its low sensitivity and the technique is essentially limited to observing water molecules in the body. Researchers are therefore constantly working on different ways of improving MRI. A major breakthrough was achieved around 20 years ago when hyperpolarized magnetic resonance imaging was first developed: Because hyperpolarized molecules emit significantly stronger MRI signals, substances that are only present in low concentrations in the body can also be visualized. By hyperpolarizing biomolecules and introducing them in patients, it is possible to track metabolism in real time, thus providing doctors with much more information.

Hyperpolarized fumarate is a promising biosensor for the imaging of metabolic processes. Fumarate is a metabolite of the citric acid cycle that plays an important role in the energy production of living beings. For imaging purposes, the fumarate is tagged with carbon-13 as the atomic nuclei of this isotope can be hyperpolarized. Dynamic nuclear polarization is the current state-of-the-art method for hyperpolarizing fumarate, but this is expensive and relatively slow. The equipment required costs one to two million euros. “Dynamic nuclear polarization is very difficult to use in everyday clinical practice due to the related high costs and technical complexity. Using parahydrogen, we are able to hyperpolarize this important biomolecule in a cost-effective and convenient way,” said Dr. Stephan Knecht of TU Darmstadt, the first author of the published article.

A new method to hyperpolarize and purify fumarate for subsequent use as a biosensor

The research team led by Dr. James Eills has already been working on this concept for some time. “We have made a significant breakthrough as our approach is not only cheap, but also fast and easy to handle,” emphasized Eills. However, parahydrogen-induced polarization, or PHIP for short, also has its disadvantages. The low level of polarization and the large number of unwanted accompanying substances are particularly problematic in the case of this chemistry-based technique. Among other things, transferring the polarization from parahydrogen into fumarate requires a catalyst, which remains in the reaction fluid just like other reaction side-products. “The chemical contaminants must be removed from the solution so it is biocompatible and can be injected in living beings. This is essential if we think about the future clinical translation of this hyperpolarized biosensor,” said Dr. Eleonora Cavallari, a physicist from the Department of Molecular Biotechnology and Health Sciences in Turin.

The solution to this problem is to purify the hyperpolarized fumarate through precipitation. The fumarate then takes the form of a purified solid and can be redissolved at the desired concentration later. “This means we have a product from which all toxic substances have been removed so that it can readily be used in the body,” added Dr. James Eills. In addition, compared to previous experiments with PHIP, the polarization is increased to remarkable 30 to 45 percent. Preclinical studies have already shown that hyperpolarized fumarate imaging is a suitable method of monitoring how tumors respond to therapy as well as for imaging acute kidney injuries or the effects of myocardial infarction. This new way of producing hyperpolarized fumarate should greatly accelerate preclinical studies and bring this technology to more laboratories.

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Hyperpolarized fumarate is a promising biosensor for the imaging of metabolic processes. Fumarate is a metabolite of the citric acid cycle that plays an important role in the energy production of living beings. For imaging purposes, the fumarate is tagged with carbon-13 as the atomic nuclei of this isotope can be hyperpolarized. Dynamic nuclear polarization is the current state-of-the-art method for hyperpolarizing fumarate, but this is expensive and relatively slow. The equipment required costs one to two million euros. “Dynamic nuclear polarization is very difficult to use in everyday clinical practice due to the related high costs and technical complexity. Using parahydrogen, we are able to hyperpolarize this important biomolecule in a cost-effective and convenient way,” said Dr. Stephan Knecht of TU Darmstadt, the first author of the published article.

Source: https://bioengineer.org/metabolite-fumarate-can-reveal-cell-damage-new-method-to-generate-fumarate-for-mri/

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Skoltech researchers propose a new data-driven tool to better understand startups

Credit: Malyy et al., 2021 Skoltech researchers used Google Trends’ Big Data ensuing from human interactions with the Internet to

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Skoltech researchers used Google Trends’ Big Data ensuing from human interactions with the Internet to develop a new methodology – a tool and a data source – for analyzing and researching the growth of startups. A paper reporting these important findings was published in technology management journal, Technological Forecasting and Social Change.

Startups and high-growth technology-based ventures they transform into are regarded as the key drivers of economic development, innovation, and job creation on the national and global level. However, despite their crucial importance for the economy and high interest from researchers and policy-makers, startups display growth patterns that are difficult to analyze. These fragile, early-stage private businesses, which may quickly scale up, do not have time, interest, or obligation to share much data about what they achieved, when, or how. Thus, to outside observers, startups look like “black boxes” whose progress can hardly be assessed due to a lack of objective information.

Maksim Malyy, a PhD student from the Skoltech Center for Entrepreneurship and Innovation (CEI), has been intrigued by this problem since he worked in a startup accelerator in St. Petersburg before joining Skoltech. Looking into theoretical and practical aspects of the problem for the last three years, Maksim, his supervisor, professor Zeljko Tekic, and Skoltech assistant professor Tatiana Podladchikova came up with valuable insights on how to deal with the data scarcity problem in studying startups. Some of their findings were published in the paper.

Maksim explains why this research is so important: We demonstrate that web-search traffic information, in particular Google Trends data, can serve as a valuable source of high-quality data for analyzing the advancement of startups and growth-oriented technology-based new ventures they evolve into. We analyzed a large and transparently selected set of US based companies and showed the existence of a strong correlation between the curves based on Google searches by company name and those depicting valuations achieved through a series of investment rounds.

According to the authors, this correlation enables using Google Trends data as a proxy measure of growth instead of non-public and rarely available measures like sales, employee and market share growth. Google Trends data, which are public, easy to collect and available for almost any company since its inception, can help in building more accurate and even real-time data-driven growth paths for startups. With these evolution curves, one could revisit some old answers, ask new questions, and come up with more solid concepts, theories, and predictions.

Maksim believes that this study has strong implications for start-up research: Our findings suggest that for startups, especially thriving unicorns or B2C digital platforms, the proposed approach may become an equivalent of an X-ray scan, offering a cheap, easy, and non-invasive way to understand the workings of a technology-based new venture.

By way of comment, professor Tekic and professor Podladchikova cite a report by one of the reviewers: “I think this paper will stand the test of time and be useful for many years to come. It truly is a fascinating study.”

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https://www.skoltech.ru/en/2021/04/skoltech-researchers-propose-a-new-data-driven-tool-to-better-understand-startups/

Maksim believes that this study has strong implications for start-up research: Our findings suggest that for startups, especially thriving unicorns or B2C digital platforms, the proposed approach may become an equivalent of an X-ray scan, offering a cheap, easy, and non-invasive way to understand the workings of a technology-based new venture.

Source: https://bioengineer.org/skoltech-researchers-propose-a-new-data-driven-tool-to-better-understand-startups/

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Trial of existing antibiotic for treating Staphylococcus aureus Bacteremia begins

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