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Tag: Biotech

  • Lab-made antibodies offer potential cure for yellow fever

    Lab-made antibodies offer potential cure for yellow fever

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    Newswise — PORTLAND, Oregon — New research from Oregon Health & Science University and collaborators indicates lab-made antibodies may be able to cure people infected with yellow fever, a virus for which there is no treatment.

    The natural immune response to invading pathogens normally involves making protective proteins called antibodies. A study published today in Science Translational Medicine suggests that a single monoclonal antibody infusion can strengthen the body’s fight against yellow fever.

    In the study, the yellow fever virus was undetectable in all animals that received monoclonal antibody infusions after being exposed to the virus.

    “Two monoclonal antibodies that we evaluated completely removed all signs of infection from research animals,” said the study’s corresponding author, Ben Burwitz, Ph.D., associate professor at OHSU’s Vaccine and Gene Therapy Institute and affiliate associate professor at OHSU’s Oregon National Primate Research Center.

    The collaborative research is a joint effort between scientists from OHSU, George Washington University, the biotechnology company Mabloc, LLC, and other organizations. Mabloc plans to use these findings to inform a future clinical trial in humans, in addition to their product development efforts.

    “Neglected tropical diseases like yellow fever, dengue and Zika are often overlooked by traditional pharmaceutical development, but we hope monoclonal antibody technology will change that,” said David Watkins, Ph.D., co-senior author on the study, professor of pathology at George Washington University and Mabloc’s chief executive officer. 

    “By showing such efficacy in a primate model that mimics severe human disease, we hope to advance this to clinical trials and be ready to deploy treatments for the next outbreak of yellow fever,” said the study’s first author, Michael Ricciardi, Ph.D., associate director of translational research at George Washington University and Mabloc’s director of product development.  

    Increasingly common yellow fever 

    As many as half of people who get severe yellow fever die from the virus, which causes flu-like symptoms and can lead to jaundice and organ failure in more serious cases. Every year, the virus infects about 200,000 people — killing about 30,000 worldwide. 

    Currently, most cases occur in tropical and sub-tropical areas of Africa and South America, but global climate change is expected to increase the range of the mosquitoes that spread the virus. Deaths in Africa alone are predicted to increase by 25% by the year 2050. 

    The disease is preventable with a highly effective vaccine, which has been available since the 1930s. Although the vaccine is safe for the vast majority of people, vaccine hesitancy leaves some vulnerable to infection. It is a live vaccine that uses a weakened form of the virus, which causes a very small percentage of recipients to experience an adverse reaction that has been fatal in rare cases. A treatment could benefit both unvaccinated individuals who get sick and the very few people who experience a vaccine-related reaction.

    When they began considering potential yellow fever treatments, the research team initially considered 37 antibodies cloned from people who had been vaccinated against yellow fever. The team then narrowed its focus to two monoclonal antibodies capable of controlling variants of the virus that were involved in recent yellow fever outbreaks. 

    The team manufactured these two monoclonal antibodies in the lab and studied how protective they could be against the yellow fever virus in two animal species: rhesus macaque monkeys and hamsters. After animals were exposed to the virus, each species was divided into three groups: one group that received the first antibody, another that received the second antibody, and a third that didn’t receive either antibody. 

    The virus couldn’t be detected in blood samples of any of the animals – eight rhesus macaques and 20 hamsters – that received either monoclonal antibody. All those in the control group developed severe disease. While one treated hamster died of an unknown cause, it neither showed signs of a yellow fever infection nor did it have signs of an adverse reaction to the monoclonal antibody.

    Both monoclonal antibody candidates also appeared to be safe. None of the animals that received either experimental treatment displayed liver dysfunction, a tell-tale sign of severe yellow fever infection and yellow fever vaccine-associated disease.

     

    This research was supported by the National Institutes of Health (grants R42 AI155275 and P51 OD01092) and by Mabloc, LLC.

    Some of the researchers involved in this study — including Jonah Sacha, Ph.D., of OHSU; and Michael Ricciardi, Ph.D., and David Watkins, Ph.D., of George Washington University — have a significant financial interest in Mabloc, LLC, a company that may have a financial interest in the results of this research and technology. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU.

    All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals. 

     

    REFERENCE: Michael J. Ricciardi, Lauren N. Rust, Nuria Pedreno-Llpez, Sofiya Yusova, Sreya Biswas, Gabriela M. Webb, Lucas Gonzalez-Nieto, Thomas B. Voigt, Johan J. Louw, Fernanda D. Laurino, John R. DiBello, Hans-Peter Raue, Aaron M. Barber-Axthelm, Kimberly Chun, Samantha Uttke, Lidiane M.S. Raphael, Aaron Yrizarry-Medina, Brandon C. Rosen, Rebeca Agnor, Lina Gao, Caralyn Labriola, Michael Axthelm, Jeremy Smedley, Justin G. Julander, Myrna C. Bonaldo, Laura M. Walker, Ilhem Messaoudi, Mark K. Slikfa, Dennis R. Burton, Esper G. Kallas, Jonah B. Sacha, David I. Watkins,  Benjamin J. Burwitz, Therapeutic neutralizing monoclonal antibody administration protects against lethal yellow virus infection, Science Translational Medicine, March 29, 2023, https://doi.org/10.1126/scitranslmed.ade5795

     

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    Oregon Health & Science University

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  • Technology to protect bioactive compounds from food during digestion

    Technology to protect bioactive compounds from food during digestion

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    Newswise — Bioactive compounds present mostly in fruit and vegetables perform different bodily functions relating to health and well-being. Their effects are considered antioxidant, antidiabetic, antiaging and anticancer, among others.

    Many studies are looking for ways to optimize absorption of bioactive compounds by the organism and increase their bioavailability – the proportion that enters the bloodstream after absorption. One way is to coat the compounds with another material and package them on the nanometric scale (a nanometer is a billionth of a meter). Nanoencapsulation, as this technique is known, assures slow release of the compounds so that they take longer to digest and can survive the attacks of bacteria in the gut microbiome.

    An investigation conducted by a duo of researchers at the University of São Paulo’s School of Pharmaceutical Sciences (FCF-USP) in Brazil is one of these studies. Working at the school’s Department of Food Science and Experimental Nutrition, they have produced several articles on the subject – the latest of which, published in the International Journal of Biological Macromolecules, is a review of the literature on pectin-based nanoencapsulation plus a description of a novel technology developed under the aegis of the Food Research Center (FoRC), a Research, Innovation and Dissemination Center (RIDC) supported by FAPESP.

    “We used pectin extracted from residues of citrus fruit albedo and peel, with a degree of purity permitting human ingestion and excluding any kind of hazardous chemical,” said João Paulo Fabi, one of the authors and a professor at FCF-USP. Albedo is the layer of white spongy material inside the peel of oranges and lemons, for example.

    “In addition to our review of the literature, we describe a novel technology for nanoencapsulation of bioactive compounds using pectin. This entails producing a pectin-lysozyme complex as a protective outer layer for a highly sensitive bioactive compound called anthocyanin,” he explained, adding that lysozyme is “a safely edible substance obtained from egg white and used to enhance the stability of the end-product”.

    Anthocyanins are water-soluble pigments belonging to the flavonoid family. They are phenolic compounds found in all plants and responsible for the shades of red, blue and purple seen in flowers, fruit, leaves, stalks and roots.

    The authors say their methodology can be used to encapsulate other water-soluble bioactive compounds. “We tested anthocyanin because of its challenging sensitivity to many factors, such as light, temperature, pH and gut bacteria,” said Thiécla Katiane Osvaldt Rosales, the other author. She is currently a postdoctoral researcher at the Nuclear and Energy Research Institute (IPEN).

    Besides FoRC, FAPESP also funded the research via support for two other projects (19/11816-8 and 12/23970-2). 

    Advantages of methodology

    According to the researchers, the main advantage of their methodology is that no other compounds are added apart from pectin, lysozyme and anthocyanin. “We used three compounds from sources in nature and mixed them in the laboratory to form a new product, without adding salts, ligands or anything potentially toxic. Furthermore, the nanoparticles are not too small. Very tiny nanoparticles can penetrate barriers and cell membranes, entering the DNA and having toxic effects. The size we obtained is safe,” Fabi said.

    Rosales outlined the process they developed to produce the nanoparticles. “Pectin and lysozyme are heated separately. The increase in temperature partly alters their structure, and they interact better when heated. They are then rapidly cooled to reach a temperature not harmful to anthocyanin, which is sensitive and fairly unstable. The three substances are blended in an aqueous suspension and agitated for an hour. The result is encapsulated anthocyanin. The suspension is then filtered to separate the non-encapsulated contents,” she said.

    Special care is taken with factors such as temperature and pH. “We tested the parameters for the purpose of optimization, especially pH. If pH is too high, the anthocyanin breaks down. It can’t be too low, either. We found a pH of 5 to be optimal for interaction between the molecules,” she explained. “We also tested the duration and intensity of the agitation. We made a point of managing all the details, however minor, because they make a difference in terms of forming stable particles. We’ve applied for a patent on the methodology.”

    Results

    Finally, the encapsulation was tested for efficacy in a digestion system simulated in the laboratory to mimic the gastric and intestinal phases. “The result was that part of the anthocyanin was released during the digestive process, at the end of gastric digestion, and part remained in the nanostructure, with the possibility of release of this remainder in the gut or absorption together with the nanostructure. We believe this was a good outcome. Partial and gradual release suggests absorption of the compound starts before it enters the gut, with the nanoencapsulated remainder probably being released in the gut or fully absorbed with less structural alteration,” Rosales said.

    The next step will be animal testing. “We tested the method in vitro and obtained results indicating that the nanoparticles are safe for consumption. We have evidence that cells can absorb them in a non-toxic manner and that the pectin protects the anthocyanin and its properties. We now have to test it in animals, observing the process of oral ingestion, absorption of the anthocyanin using specific markers for absorption, and the route followed in the organism. It’s important to verify the extent of absorption and the biological destination,” she said.

    The nanoparticles are mainly intended for use as a food supplement. “They can be added to food and dietary supplements, but industrial mass production would be necessary to include them in a supplement,” Fabi said.

    It is worth noting that the method does not require expensive equipment or procedures. “In addition, the material used for the nanocapsules, which comes from byproducts of citrus peel, would make the cost even lower for manufacturers. The pectin we used in our study is available commercially and is used by the food industry, mostly for gel formation in jam or as a thickener,” Rosales said.

    About São Paulo Research Foundation (FAPESP)

    The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

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    Sao Paulo Research Foundation (FAPESP)

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  • Mammalian Ste20-like kinase 1 inhibition as a cellular mediator of anoikis in mouse bone marrow mesenchymal stem cells

    Mammalian Ste20-like kinase 1 inhibition as a cellular mediator of anoikis in mouse bone marrow mesenchymal stem cells

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    BACKGROUND

    The low survival rate of mesenchymal stem cells (MSCs) caused by anoikis, a form of apoptosis, limits the therapeutic efficacy of MSCs. As a proapoptotic molecule, mammalian Ste20-like kinase 1 (Mst1) can increase the production of reactive oxygen species (ROS), thereby promoting anoikis. Recently, we found that Mst1 inhibition could protect mouse bone marrow MSCs (mBMSCs) from H2O2-induced cell apoptosis by inducing autophagy and reducing ROS production. However, the influence of Mst1 inhibition on anoikis in mBMSCs remains unclear.

    AIM

    To investigate the mechanisms by which Mst1 inhibition acts on anoikis in isolated mBMSCs.

    METHODS

    Poly-2-hydroxyethyl methacrylate-induced anoikis was used following the silencing of Mst1 expression by short hairpin RNA (shRNA) adenovirus transfection. Integrin (ITGs) were tested by flow cytometry. Autophagy and ITGα5β1 were inhibited using 3-methyladenine and small interfering RNA, respectively. The alterations in anoikis were measured by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling and anoikis assays. The levels of the anoikis-related proteins ITGα5, ITGβ1, and phospho-focal adhesion kinase and the activation of caspase 3 and the autophagy-related proteins microtubules associated protein 1 light chain 3 II/I, Beclin1 and p62 were detected by Western blotting.

    RESULTS

    In isolated mBMSCs, Mst1 expression was upregulated, and Mst1 inhibition significantly reduced cell apoptosis, induced autophagy and decreased ROS levels. Mechanistically, we found that Mst1 inhibition could upregulate ITGα5 and ITGβ1 expression but not ITGα4, ITGαv, or ITGβ3 expression. Moreover, autophagy induced by upregulated ITGα5β1 expression following Mst1 inhibition played an essential role in the protective efficacy of Mst1 inhibition in averting anoikis.

    CONCLUSION

    Mst1 inhibition ameliorated autophagy formation, increased ITGα5β1 expression, and decreased the excessive production of ROS, thereby reducing cell apoptosis in isolated mBMSCs. Based on these results, Mst1 inhibition may provide a promising strategy to overcome anoikis of implanted MSCs.

    Key Words: Mouse bone marrow mesenchymal stem cell, Mammalian sterile 20-like kinase 1, Anoikis, Integrin, Autophagy, Reactive oxygen species

     

    Core Tip: In isolated mouse bone marrow mesenchymal stem cell (mBMSCs), Mammalian sterile 20-like kinase 1 (Mst1) inhibition could ameliorate not only autophagy formation but also upregulate integrin (ITG) α5β1 expression (but not ITGα4, ITGαv, or ITGβ3). In addition, Mst1 inhibition-induced autophagy could scavenge the excessive production of ITGα5β1-triggered ROS. Therefore, Mst1 inhibition-based infusion may improve the survival of MSCs, thereby serving as an ideal candidate for clinical transplantation in pulmonary arterial hypertension.

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    World Journal of Stem Cells

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  • Clinical trials using dental stem cells: 2022 update

    Clinical trials using dental stem cells: 2022 update

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    For nearly 20 years, dental stem cells (DSCs) have been successfully isolated from mature/immature teeth and surrounding tissue, including dental pulp of permanent teeth and exfoliated deciduous teeth, periodontal ligaments, dental follicles, and gingival and apical papilla. They have several properties (such as self-renewal, multidirectional differentiation, and immunomodulation) and exhibit enormous potential for clinical applications. To date, many clinical articles and clinical trials using DSCs have reported the treatment of pulpitis, periapical lesions, periodontitis, cleft lip and palate, acute ischemic stroke, and so on, and DSC-based therapies obtained satisfactory effects in most clinical trials. In these studies, no adverse events were reported, which suggested the safety of DSC-based therapy. In this review, we outline the characteristics of DSCs and summarize clinical trials and their safety as DSC-based therapies. Meanwhile, we also present the current limitations and perspectives of DSC-based therapy (such as harvesting DSCs from inflamed tissue, applying DSC-conditioned medium/DSC-derived extracellular vesicles, and expanding-free strategies) to provide a theoretical basis for their clinical applications.

    Core Tip: Since dental pulp stem cells were first isolated and identified in 2000, a variety of dental stem cells (DSCs) have been reported. DSCs have shown satisfactory clinical effects in the treatment of a variety of diseases and have great potential for clinical application. This paper will summarize DSC-based clinical trials and put forward the current limitations and perspectives to accelerate and extend the clinical application of DSCs.

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    World Journal of Stem Cells

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  • ‘Smart’ bandages monitor wounds and provide targeted treatment

    ‘Smart’ bandages monitor wounds and provide targeted treatment

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    Newswise — Most of the time, when someone gets a cut, scrape, burn, or other wound, the body takes care of itself and heals on its own. But this is not always the case. Diabetes can interfere with the healing process and create wounds that will not go away and that could become infected and fester.

    These kinds of chronic wounds are not just debilitating for the people suffering from them. They are also a drain on healthcare systems, representing a $25 billion financial burden in the United States alone each year.

    A new kind of smart bandage developed at Caltech may make treatment of these wounds easier, more effective, and less expensive. These smart bandages were developed in the lab of Wei Gao, assistant professor of medical engineering, Heritage Medical Research Institute Investigator, and Ronald and JoAnne Willens Scholar.

    “There are many different types of chronic wounds, especially in diabetic ulcers and burns that last a long time and cause huge issues for the patient,” Gao says. “There is a demand for technology that can facilitate recovery.”

    Unlike a typical bandage, which might only consist of layers of absorbent material, the smart bandages are made from a flexible and stretchy polymer containing embedded electronics and medication. The electronics allow the sensor to monitor for molecules like uric acid or lactate and conditions like pH level or temperature in the wound that may be indicative of inflammation or bacterial infection.

    The bandage can respond in one of three ways: First, it can transmit the gathered data from the wound wirelessly to a nearby computer, tablet, or smartphone for review by the patient or a medical professional. Second, it can deliver an antibiotic or other medication stored within the bandage directly to the wound site to treat the inflammation and infection. Third, it can apply a low-level electrical field to the wound to stimulate tissue growth resulting in faster healing.

    In animal models under laboratory conditions, the smart bandages showed the ability to provide real-time updates about wound conditions and the animals’ metabolic states to researchers, as well as offer speed healing of chronic infected wounds similar to those found in humans.

    Gao says the results are promising and adds that future research in collaboration with the Keck School of Medicine of USC will focus on improving the bandage technology and testing it on human patients, whose therapeutic needs may be different than those of lab animals.

    “We have showed this proof of concept in small animal models, but down the road, we would like to increase the stability of the device but also to test it on larger chronic wounds because the wound parameters and microenvironment may vary from site to site,” he says.

    The paper describing the research, “A stretchable wireless wearable bioelectronic system for multiplexed monitoring and combination treatment of infected chronic wounds,” appears in the March 24 issue of the journal Science Advances. Co-authors are postdoctoral scholar research associates in medical engineering Ehsan Shirzaei Sani and Yu Song; medical engineering graduate students Changhao Xu (MS ’20), Canran Wang, Jihong Min (MS ’19), Jiaobing Tu (MS ’20), Samuel A. Solomon, and Jiahong Li; and Jaminelli L. Banks and David G. Armstrong of the Keck School of Medicine of USC.

    Funding for the research was provided by the National Institutes of Health, the National Science Foundation, the Office of Naval Research, the Heritage Medical Research Institute, the Donna and Benjamin M. Rosen Bioengineering Center at Caltech, the Rothenberg Innovation Initiative at Caltech, and a Sloan Research Fellowship.

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    California Institute of Technology

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  • Tackling counterfeit seeds with “unclonable” labels

    Tackling counterfeit seeds with “unclonable” labels

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    Newswise — Average crop yields in Africa are consistently far below expected, and one significant reason is the prevalence of counterfeit seeds whose germination rates are far lower than those of the genuine ones. The World Bank estimates that as much as half of all seeds sold in some African countries are fake, which could help to account for crop production that is far below potential.

    There have been many attempts to prevent this counterfeiting through tracking labels, but none have proved effective; among other issues, such labels have been vulnerable to hacking because of the deterministic nature of their encoding systems. But now, a team of MIT researchers has come up with a kind of tiny, biodegradable tag that can be applied directly to the seeds themselves, and that provides a unique randomly created code that cannot be duplicated.

    The new system, which uses minuscule dots of silk-based material, each containing a unique combination of different chemical signatures, is described today in the journal Science Advances in a paper by MIT’s dean of engineering Anantha Chandrakasan, professor of civil and environmental engineering Benedetto Marelli, postdoc Hui Sun, and graduate student Saurav Maji.

    The problem of counterfeiting is an enormous one globally, the researchers point out, affecting everything from drugs to luxury goods, and many different systems have been developed to try to combat this. But there has been less attention to the problem in the area of agriculture, even though the consequences can be severe. In sub-Saharan Africa, for example, the World Bank estimates that counterfeit seeds are a significant factor in crop yields that average less than one-fifth of the potential for maize, and less than one-third for rice. 

    Marelli explains that a key to the new system is creating a randomly-produced physical object whose exact composition is virtually impossible to duplicate. The labels they create “leverage randomness and uncertainty in the process of application, to generate unique signature features that can be read, and that cannot be replicated,” he says.

    What they’re dealing with, Sun adds, “is the very old job of trying, basically, not to get your stuff stolen. And you can try as much as you can, but eventually somebody is always smart enough to figure out how to do it, so nothing is really unbreakable. But the idea is, it’s almost impossible, if not impossible, to replicate it, or it takes so much effort that it’s not worth it anymore.”

    The idea of an “unclonable” code was originally developed as a way of protecting the authenticity of computer chips, explains Chandrakasan, who is the Vannevar Bush Professor of Electrical Engineering and Computer Science. “In integrated circuits, individual transistors have slightly different properties coined device variations,” he explains, “and you could then use that variability and combine that variability with higher-level circuits to create a unique ID for the device. And once you have that, then you can use that unique ID as a part of a security protocol. Something like transistor variability is hard to replicate from device to device, so that’s what gives it its uniqueness, versus storing a particular fixed ID.” The concept is based on what are known as physically unclonable functions, or PUFs.

    The team decided to try to apply that PUF principle to the problem of fake seeds, and the use of silk proteins was a natural choice because the material is not only harmless to the environment but also classified by the Food and Drug Administration in the “generally recognized as safe” category, so it requires no special approval for use on food products.

    “You could coat it on top of seeds,” Maji says, “and if you synthesize silk in a certain way, it will also have natural random variations. So that’s the idea, that every seed or every bag could have a unique signature.”

    Developing effective secure system solutions have long been one of Chandrakasan’s specialties, while Marelli has spent many years developing systems for applying silk coatings to a variety of fruits, vegetables, and seeds, so their collaboration was a natural for developing such a silk-based coding system towards enhanced security. 

    “The challenge was what type of form factor to give to silk,” Sun says, “so that it can be fabricated very easily.” They developed a simple drop-casting approach that produces tags that are less than one-tenth of an inch in diameter. The second challenge was to develop “a way where we can read the uniqueness, in also a very high throughput and easy way.”

    For the unique silk-based codes, Marelli says, “eventually we found a way to add a color to these microparticles so that they assemble in random structures.” The resulting unique patterns can be read out not only by a spectrograph or a portable microscope, but even by an ordinary cellphone camera with a macro lens. This image can be processed locally to generate the PUF code and then sent to the cloud and compared with a secure database to ensure the authenticity of the product. “It’s random so that people cannot easily replicate it,” says Sun. “People cannot predict it without measuring it.”

    And the number of possible permutations that could result from the way they mix four basic types of colored silk nanoparticles is astronomical. “We were able to show that with a minimal amount of silk, we were able to generate 128 random bits of security,” Maji says. “So this gives rise to 2 to the power 128 possible combinations, which is extremely difficult to crack given the computational capabilities of the state-of-the-art computing systems.”

    Marelli says that “for us, it’s a good test bed in order to think out-of-the-box, and how we can have a path that somehow is more democratic.” In this case, that means “something that you can literally read with your phone, and you can fabricate by simply drop casting a solution, without using any advanced manufacturing technique, without going in a clean room.”

    Some additional work will be needed to make this a practical commercial product, Chandrakasan says. “There will have to be a development for at-scale reading” via smartphones. “So. that’s clearly a future opportunity.” But the principle now shows a clear path to the day when “a farmer could at least, maybe not every seed, but could maybe take some random seeds in a particular batch and verify them,” he says.

    The research was partially supported by the U.S. Office of Naval research and the National Science Foundation, Analog Devices Inc., an EECS Mathworks fellowship, and a Paul M. Cook Career Development Professorship.

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    Massachusetts Institute of Technology (MIT)

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  • Antibiotic resistance is an increasing problem. Learn all about it in the Drug Resistance channel.

    Antibiotic resistance is an increasing problem. Learn all about it in the Drug Resistance channel.

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    Staphylococcus aureus, Clostridioides difficile, Candida auris, Drug-resistant Shigella. These bacteria not only have difficult names to pronounce, but they are also difficult to fight off.  These bacteria may infect humans and animals, and the infections they cause are harder to treat than those caused by non-resistant bacteria. Antimicrobial resistance is an urgent global public health threat. According to the World Health Organization, antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality. It kills at least 1.27 million people worldwide and they are associated with nearly 5 million deaths in 2019, according to the CDC. In the U.S., more than 2.8 million antimicrobial-resistant infections occur each year. Careful prescribing of antibiotics will minimize the development of more antibiotic-resistant strains of bacteria. Staying informed is another way to fight these dangerous “superbugs.” Below are some of the latest news updates on the topic of Drug Resistance.

    Scientists make critical progress toward preventing C. diff infections (embargoed until 26-Mar-2023 5:00 PM EDT)

    Resistant bacteria are a global problem. Now researchers may have found the solution

    Potential Treatment Target for Drug-Resistant Epilepsy Identified

    Brazilian researchers investigate diversity of E. coli bacteria in hospitalized patients

    A Quick New Way to Screen Virus Proteins for Antibiotic Properties

    New Class of Drugs Could Prevent Resistant COVID-19 Variants

    The world’s first mRNA vaccine for deadly bacteria

    From anti-antibiotics to extinction therapy: how evolutionary thinking can transform medicine

    St. Jude approach prevents drug resistance and toxicity

    Restricting antibiotics for livestock could limit spread of antibiotic-resistant infections in people

    Resistance Is Futile

    Bacteria communicate like us – and we could use this to help address antibiotic resistance

    Study reveals how drug resistant bacteria secrete toxins, suggesting targets to reduce virulence

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    Newswise

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  • DOE funds next-generation Center for Bioenergy Innovation at ORNL to advance renewable jet fuel

    DOE funds next-generation Center for Bioenergy Innovation at ORNL to advance renewable jet fuel

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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:

    • Developing perennial crops that require less water and fertilizer and yield high amounts of biomass with the desired qualities for conversion to bioproducts.
    • Refining an efficient, cost-effective consolidated bioprocessing and co-treatment process using custom microbes to break down plants and ferment intermediate chemicals.
    • Advancing the extraction of lignin from plants and chemically converting it into aviation fuel.
    • Improving the chemical catalyst-based upgrading of intermediate bioproducts into jet fuel that can be blended with conventional fuel to significantly reduce aircraft carbon emissions.

    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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  • Microbes can create a more peaceful world: Scientists call to action

    Microbes can create a more peaceful world: Scientists call to action

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    Newswise — Microorganisms should be ‘weaponised’ to stave off conflicts across the globe, according to a team of eminent microbiologists. 

    The paper ‘Weaponising microbes for peace’ by Anand et al, outlines the ways in which microbes and microbial technologies can be used to tackle global and local challenges that could otherwise lead to conflict, but warns that these resources have been severely underexploited to date. 

    Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology, says that worldwide deficits and asymmetries in basic resources and services considered to be human rights, such as drinking water, sanitation, healthy nutrition, access to basic healthcare and a clean environment, can lead to competition between peoples for limited resources, tensions, and in some cases conflicts. 

    “There is an urgent need to reduce such deficits, to level up, and to assure provision of basic resources for all peoples. This will also remove some of the causes of conflicts. There is a wide range of powerful microbial technologies that can provide or contribute to this provision of such resources and services, but deployment of such technologies is seriously underexploited,” Professor Timmis said. 

    The paper then lists a series of ways in which microbial technologies can contribute to challenges such as food supply and security, sanitation and hygiene, healthcare, pollution, energy and heating, and mass migrations and overcrowding. For example, microbes are at the core of efforts to tackle pollution by bioremediation, replacing chemical methods of treating drinking water with metalloid conversion systems, and producing biofuels from wastes. 

    “There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations,” Professor Timmis said..  

    “Not only will this contribute to the improvement of humanitarian conditions and levelling up, and thereby to a reduction in tensions that may lead to conflicts, but also advance progress towards attainment of Sustainable Development Goals,” he said. . 

    “In this paper, we draw attention to the wide range of powerful microbial technologies that can be deployed for this purpose and how sustainability can be addressed at the same time. We must weaponise microbes for peace.”

    RECOMMENDED ACTIONS TO IMPLEMENT RELEVANT MICROBIAL TECHNOLOGY SOLUTIONS TO DEFICITS 

    We need to urgently supply to communities lacking adequate levels of basic resources/services the infrastructure and know-how (capacity building), and funding for 

    1. use of agrobiologics to increase crop yields, by providing green nitrogen, stimulating plant growth, and combatting pathogens and pests, 

    2. exploitation of plant:microbe partnerships to improve soil health and implement regenerative agriculture, 

    3. creation of nutritious fermented food from locally available crops, 

    4. better use of microbes in the feed and food supply chains, 

    5. production of microbial food for humans and farm animals, 

    6. drinking water production and quality safeguarding, 

    7. waste treatment with resource recovery, 

    8. creation of modular DIY digital medical centres, 

    9. production of vaccines and medicines, 

    10. bioremediation and biorestoration of the environment in general and natural ecosystems in particular, to create healthier habitats and promote biodiversity 

    11. reduction of greenhouse gas production and capturing carbon, 

    12. production of biofuels, 

    13. creation of local employment opportunities associated with the above, 

    14. development of transdisciplinary approaches, using chemistry-related, computation technologies, psychology-related and other approaches that are synergistic to microbial solutions and 

    15. education in societally relevant microbiology 

    ‘Weaponising microbes for peace’ is published in Microbial Biotechnology, an Applied Microbiology International publication, on March 7 2023. 

    The authors are Shailly Anand, John E. Hallsworth, James Timmis, Willy Verstraete, Arturo Casadevall, Juan Luis Ramos, Utkarsh Sood, Roshan Kumar, Princy Hira, Charu Dogra Rawat, Abhilash Kumar, Sukanya Lal, Rup Lal, Kenneth Timmis. 

    To read the full paper, click HERE. 

    To find out more about AMI, visit https://appliedmicrobiology.org/ or https://www.the-microbiologist.com/. 

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    Applied Microbiology International

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  • 12 exotic bacteria found to passively collect rare earth elements from wastewater

    12 exotic bacteria found to passively collect rare earth elements from wastewater

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    Newswise — Rare earth elements (REEs) are a group of 17 chemically similar metals, which got their name because they typically occur at low concentrations (between 0.5 and 67 parts per million) within the Earth’s crust. Because they are indispensable in modern technology such as light emitting diodes, mobile phones, electromotors, wind turbines, hard disks, cameras, magnets, and low-energy lightbulbs, the demand for them has increased steadily over the past few decades, and is predicted to rise further by 2030.

    As a result of their rarity and the demand they are expensive: for example, a kilo of neodymium oxide currently costs approximately €200, while the same amount of terbium oxide costs approximately €3,800. Today, China has a near-monopoly on the mining of REEs, although the discovery of promising new finds (more than one million metric tons) in Kiruna, Sweden was announced with great fanfare in January 2023.

    Circular economy

    The advantages of moving from a wasteful ‘linear’ economy to a ‘circular’ economy, where all resources are recycled and reused, are obvious. So could we recycle REEs more efficiently, too?

    In Frontiers in Bioengineering and Biotechnology, German scientists showed that the answer is yes: the biomass of some exotic photosynthetic cyanobacteria can efficiently absorb REEs from wastewater, for example derived from mining, metallurgy, or the recycling of e-waste. The absorbed REEs can afterwards be washed from the biomass and collected for reuse.

    “Here we optimized the conditions of REE uptake by the cyanobacterial biomass, and characterized the most important chemical mechanisms for binding them. These cyanobacteria could be used in future eco-friendly processes for simultaneous REE recovery and treatment of industrial wastewater,” said Dr Thomas Brück, a professor at the Technical University of Munich and the study’s last author.

    Highly specialist strains of cyanobacteria

    Biosorption is a metabolically passive process for the fast, reversible binding of ions from aqueous solutions to biomass. Brück and colleagues measured the potential for biosorption of the REEs lanthanum, cerium, neodymium, and terbium by 12 strains of cyanobacteria in laboratory culture. Most of these strains had never been assessed for their biotechnological potential before. They were sampled from highly specialized habitats such as arid soils in Namibian deserts, the surface of lichens around the world, natron lakes in Chad, crevices in rocks in South Africa, or polluted brooks in Switzerland.

    The authors found that an uncharacterized new species of Nostoc had the highest capacity for biosorption of ions of these four REEs from aqueous solutions, with efficiencies between 84.2 and 91.5 mg per g biomass, while Scytonema hyalinum had the lowest efficiency at 15.5 to 21.2 mg per g. Also efficient were Synechococcus elongates, Desmonostoc muscorum, Calothrix brevissima, and an uncharacterized new species of Komarekiella. Biosorption was found to depend strongly on acidity: it was highest at a pH of between five and six, and decreased steadily in more acid solutions. The process was most efficient when there was no ‘competition’ for the biosorption surface on the cyanobacteria biomass from positive ions of other, non-REE metals such as zinc, lead, nickel, or aluminium.

    The authors used a technique called infrared spectroscopy to determine which functional chemical groups in the biomass were mostly responsible for biosorption of REEs.

    “We found that biomass derived from cyanobacteria has excellent adsorption characteristics due to their high concentration of negatively charged sugar moieties, which carry carbonyl and carboxyl groups. These negatively charged components attract positively charged metal ions such as REEs, and support their attachment to the biomass,” said first author Michael Paper, a scientist at the Technical University of Munich.

    Fast and efficient, with great potential for future applications

    The authors conclude that biosorption of REEs by cyanobacteria is possible even at low concentrations of the metals. The process is also fast: for example, most cerium in solution was biosorbed within five minutes of starting the reaction.

    “The cyanobacteria described here can adsorb amounts of REEs corresponding to up to 10% of their dry matter. Biosorption thus presents an economically and ecologically optimized process for the circular recovery and reuse of rare earth metals from diluted industrial wastewater from the mining, electronic, and chemical-catalyst producing sectors,” said Brück.

    “This system is expected to become economically feasible in the near future, as the demand and market prizes for REEs are likely to rise significantly in the coming years,” he predicted.

    ###     

    For editors / news media:

    Please link to the open access original research article “Rare earths stick to rare cyanobacteria: future potential for bioremediation and recovery of rare earth elements” in Frontiers in Bioengineering and Biotechnology in your reporting: https://www.frontiersin.org/articles/10.3389/fbioe.2023.1130939/full

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    Frontiers

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  • Mesenchymal stem cells in ischemic tissue regeneration

    Mesenchymal stem cells in ischemic tissue regeneration

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    Diseases caused by ischemia are one of the leading causes of death in the world. Current therapies for treating acute myocardial infarction, ischemic stroke, and critical limb ischemia do not complete recovery. Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders. Mesenchymal stem cells (MSCs) are the most promising option in the field of cell-based therapies, due to their secretory and immunomodulatory abilities, that contribute to ease inflammation and promote the regeneration of damaged tissues. This review presents the current knowledge of the mechanisms of action of MSCs and their therapeutic effects in the treatment of ischemic diseases, described on the basis of data from in vitro experiments and preclinical animal studies, and also summarize the effects of using these cells in clinical trial settings. Since the obtained therapeutic benefits are not always satisfactory, approaches aimed at enhancing the effect of MSCs in regenerative therapies are presented at the end.

    Core Tip: Mesenchymal stem cell (MSC) transplantation is an innovative therapy with positive therapeutic effects for many ischemic diseases. Ischemia of an area is defined as insufficient blood supply to specific tissues and various organs or individual parts of the body. The leading cause of tissue ischemia is the narrowing or blockage of the lumen of an artery, most often due to the formation of atherosclerotic plaques, thrombus, or spasms of a specific artery. Here, the potential therapeutic mechanisms of MSCs in ischemic diseases were discussed, along with examples of preclinical and clinical studies.

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    World Journal of Stem Cells

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  • 10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023

    10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023

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    Newswise — WINSTON-SALEM, NC, February 9, 2023 – The Wake Forest Institute for Regenerative Medicine (WFIRM) and the Regenerative Medicine Foundation (RMF) have announced the 20th edition of World Stem Cell Summit will be held in conjunction with the 10th annual Regenerative Medicine Essentials Course, uniquely formatted this year for both in person and virtual attendance from June 5-9, 2023.

    Produced by the non-profit RMF, and in its 20th year, the World Stem Cell Summit is the most inclusive and expansive interdisciplinary, networking, and partnering meeting in the stem cell science and regenerative medicine field. With the overarching purpose of fostering translation of biomedical research, funding, and investments targeting cures, the Summit and co-located Course serve a diverse ecosystem of stakeholders and influencers.

    From the science behind pioneering discoveries and clinical applications, to regulatory and manufacturing challenges, the Summit and the Course will provide a comprehensive look at progress to date, current challenges, new “hot” topics as well as future applications.

    The World Stem Cell Summit is the educational and networking focal point for scientists, business leaders, regulators, policy-makers, patient advocates, economic development officers, experts in law and ethics, and visionary gurus from around the world since 2003. The Regenerative Medicine Essentials Course, taught by prominent experts, features a foundational instruction into the field of regenerative medicine, with examination on the structure and function of damaged tissues and organs. 

    Joint single-track programming for the Summit and the Course – the “official course” of RMF – will be held at Wake Forest locations in the Innovation Quarter located in downtown Winston-Salem. Course founder and WFIRM Director Anthony Atala, M.D., serves as co-director with Joan Schanck, MPA, WFIRM’s Chief Education Program Officer, and RMF Executive Director Bernard Siegel, JD.

    “We welcome the World Stem Cell Summit and RMF’s partnership on this venture,” Atala said. “RMF and Bernard Siegel have provided critical leadership to the field for more than 20 years, as a catalyst for the formation of valuable collaborations, while focusing upon patient advocacy, public policy issues, advancing funding initiatives, workforce development and worldwide public awareness.”

    According to Schanck, the program is designed for clinicians, researchers, technicians, students, industry, investors and government representatives. Topics include stem cells, biomaterials, cell therapies, clinical trials, regulatory matters, pathways to market, bio-manufacturing technologies and much more.

    “The Summit and Course showcase the entire regenerative medicine ecosystem and will provide timely information to expand knowledge and provide quality solutions to deliver effective treatments and cures, sooner rather than later – all in a spirit of friendship and cooperation,” Siegel said. “In the next weeks, WFIRM and RMF will announce the strategic partners and institutions supporting this event that will reach a global audience.”

    AlphaMed Press and Stem Cells Translational Medicine, the official journal partner of RMF, endorse the Course and the Summit.

    For more information about the upcoming virtual World Stem Cell Summit, please visit: www.worldstemcellsummit.com. To receive the latest information about the RME schedule, speakers and topics, bookmark this page.

     

     

     

    About Wake Forest Institute for Regenerative Medicine: WFIRM is recognized as an international leader in translating scientific discovery into clinical therapies, with many world firsts, including the development and implantation of the first engineered organ in a patient. Over 400 people at the institute, the largest in the world, work on more than 40 different tissues and organs. A number of the basic principles of tissue engineering and regenerative medicine were first developed at the institute. WFIRM researchers have successfully engineered replacement tissues and organs in all four categories – flat structures, tubular tissues, hollow organs and solid organs – and 16 different applications of cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidney, and vaginal organs, have been successfully used in human patients. The institute, which is part of Wake Forest School of Medicine, is located in the Innovation Quarter in downtown Winston-Salem, NC, and is driven by the urgent needs of patients. The institute is making a global difference in regenerative medicine through collaborations with over 400 entities and institutions worldwide, through its government, academic and industry partnerships, its start-up entities, and through major initiatives in breakthrough technologies, such as tissue engineering, cell therapies, diagnostics, drug discovery, biomanufacturing, nanotechnology, gene editing and 3D printing. 

    About RegenMed Development Organization: The mission of the RegenMed Development Organization (ReMDO) is to accelerate the discovery and translation of regenerative medicine therapies. ReMDO is a 501(c)3 non-profit organization that manages a clinical translation initiative that includes thought leaders, representatives from leading US research centers, government representatives, and companies of all sizes. ReMDO conducts research to de-risk technologies and speed up their translation to clinical practice and to the global market. ReMDO manages the world’s first and only professional organization dedicated solely to advancing the regenerative medicine field, the Regenerative Medicine Manufacturing Society (RMMS), and the Regenerative Medicine Manufacturing Innovation Consortium (RegMIC), which manages a private-public partnership of industry and academic members focused on scaling up technologies.

    About the World Stem Cell Summit: The World Stem Cell Summit is a project of the nonprofit Regenerative Medicine Foundation. Since 2003, Regenerative Medicine Foundation has built the strongest, most comprehensive and trusted global network for Regenerative Medicine, uniting the world’s leading researchers, medical centers, universities, labs, businesses, funders, policymakers, experts in law, regulation and ethics, medical philanthropies and patient organizations. Our mission is to accelerate regenerative medicine to improve health and deliver cures. We are committed to the ethical advancement of an innovative medicine powered by regenerative, restorative, and curative technologies. All we do is in service of health, life, and the alleviation of human suffering.

    About the Regenerative Medicine Foundation: The nonprofit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF unites the world’s leading researchers, medical centers, universities, labs, businesses, funders, policymakers, experts in law, regulation and ethics, medical philanthropies, and patient organizations. We maintain a trusted network of leaders and pursue our mission by producing our flagship World Stem Cell Summit series of conferences and public days, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, supporting our official journal partner STEM CELLS Translational Medicine (SCTM), promoting solution-focused policy initiatives both nationally and internationally and creating STEM/STEAM educational projects. For more information about RMF, please visit: www.regmedfoundation.org.

     

     

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  • Rensselaer Researchers To Explore “Fast Fashion” Alternatives

    Rensselaer Researchers To Explore “Fast Fashion” Alternatives

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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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    Rensselaer Polytechnic Institute (RPI)

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  • SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS

    SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS

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    Reducing levels of a spliceosome-associated factor, SYF2, attenuates TDP-43 pathology in models of diverse forms of ALS. Therefore, these findings by Linares et al. indicate that SYF2 suppression may function as a broadly acting therapeutic strategy for the treatment of ALS.

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    Cell Stem Cell

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  • ARVO Foundation Announces 2022 Point of View Award Winner

    ARVO Foundation Announces 2022 Point of View Award Winner

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    Newswise — Rockville, Md.—The Association for Research in Vision and Ophthalmology (ARVO) congratulates Tasneem Khatib DM, FRCOphth—recipient of the 2022 Point of View Award.

    Established by the Point of View Foundation (Fundació Punt de Vista), the award provides a $20,000 cash prize in recognition of an outstanding scholarly article related to efforts to restore vision through regenerative ophthalmology, biotechnology, whole eye transplantation or other approaches. Khatib’s article is entitled:

    • Receptor-ligand replacement via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery; Science Advances; March 31, 2021 (Corresponding author: Keith Martin, MA, DM, MRCP, FRCOphth, FRANZCO, FARVO)

    “The axons of nerve cells function like a railway system, where the cargo is essential components required for the cells to survive and function,” noted Khatib. “In neurodegenerative diseases, this railway system can get damaged or blocked. We reasoned that replacing two molecules that we know work effectively together would help to repair this transport network more effectively than delivering either one alone, and that is what we found. Rather than using the standard gene therapy approach of replacing or repairing damaged genes, we used the technique to supplement these molecules in the retina…The combined approach leads to a much more sustained therapeutic effect, which is very important for a treatment aimed at a chronic degenerative disease.”

    “We are very honoured to receive this award which will help us to continue to develop translatable therapies for patients with blinding disease,” says Khatib. “While this paper reports early stage research, we believe it shows promise for helping to treat neurodegenerative diseases that have so far proved intractable. Gene therapy has already proved effective for some rare monogenic conditions, and we hope it will be similarly useful for these more complex diseases which are much more common.”

    Khatib completed her doctoral research in neurobiology and glaucoma at the Centre for Brain Repair (University of Cambridge) and her ophthalmology residency at Cambridge University Hospitals NHS Foundation Trust. She then undertook further subspecialty surgical fellowship training in glaucoma at Moorfields Eye Hospital, London. Currently, she is a postdoctoral scholar at Byers Eye Institute (Stanford Medicine) in Stanford, Calif.

    For more information about the Point of View Award, visit ARVO’s website

    # # #

    The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include approximately 10,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders. Learn more at ARVO.org.

    Established in 2001, the ARVO Foundation for Eye Research raises funds through partnerships, grants and sponsorships to support ARVO’s world-class education and career development resources for eye and vision researchers of all stages of career and education. Learn more at ARVOFoundation.org.

    Based in Spain, the Point of View Foundation (Fundació Punt de Vista) is dedicated to advancing scientific research related to disease and injuries of the eye and visual system. To learn more about their work, visit the Fundació Punt de Vista website.

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  • Farming more seaweed to be food, feed and fuel

    Farming more seaweed to be food, feed and fuel

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    Newswise — A University of Queensland-led study has shown that expanding global seaweed farming could go a long way to addressing the planet’s food security, biodiversity loss and climate change challenges.

    PhD Candidate Scott Spillias, from UQ’s School of Earth and Environmental Science, said seaweed offered a sustainable alternative to land-based agricultural expansion to meet the world’s growing need for food and materials.

    “Seaweed has great commercial and environmental potential as a nutritious food and a building block for commercial products including animal feed, plastics, fibres, diesel and ethanol,” Mr Spillias said.

    “Our study found that expanding seaweed farming could help reduce demand for terrestrial crops and reduce global agricultural greenhouse gas emissions (GHG) by up to 2.6 billion tonnes of CO2-equivalent per year.”

    Researchers mapped the potential of farming more of the 34 commercially important seaweed species using the Global Biosphere Management Model.

    They estimated the environmental benefits of a range of scenarios based on land-use changes, GHG emissions, water and fertiliser use, and projected changes in species presence by 2050.

    “In one scenario where we substituted 10 per cent of human diets globally with seaweed products, the development of 110 million hectares of land for farming could be prevented,” Mr Spillias said.

    “We also identified millions of available hectares of ocean within global exclusive economic zones* (EEZs), where farming could be developed.

    “The largest share of suitable ocean was in the Indonesian EEZ, where up to 114 million hectares is estimated to be suitable for seaweed farming.

    “The Australian EEZ also shows great potential and species diversity, with at least 22 commercially viable species and an estimated 75 million hectares of ocean being suitable.”

    Mr Spillias said many native species of seaweed in Australian waters had not yet been studied from a commercial production perspective.

    “The way I like to look at this is to think about ancestral versions of everyday crops – like corn and wheat – which were uninspiring, weedy things,” he said.

    “Through thousands of years of breeding we have developed the staple crops that underpin modern societies and seaweed could very well hold similar potential in the future.”

    UQ study collaborator Professor Eve McDonald-Madden said the seaweed solution would have to be carried out with care, to avoid displacing problems from the land to the ocean.

    “Our study points out what could be done to address some of the mounting problems of global sustainability facing us, but it can’t be implemented without exercising extreme caution,” she said.

    This research was published in Nature Sustainability.

    UQ acknowledges the collaborative efforts of researchers from the International Institute for Applied Systems Analysis, CSIRO and the University of Tasmania.

    *An area of the sea in which a sovereign state has special rights regarding the exploration and use of marine resources, including energy production from water and wind.

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    University of Queensland

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  • Beans IN toast could revolutionise British diet

    Beans IN toast could revolutionise British diet

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    Newswise — Researchers and chefs at the University of Reading aim to encourage British consumers and food producers to switch to bread containing faba beans (commonly known as broad beans), making it healthier and less damaging to the environment.

    The £2 million, three-year, publicly-funded ‘Raising the Pulse’ project has officially begun and is announced today (18 January 2023) in the Nutrition Bulletin journal.

    Five teams of researchers within the University of Reading, along with members of the public, farmers, industry, and policy makers, are now working together to bring about one of the biggest changes to UK food in generations.

    This is by increasing pulses in the UK diet, particularly faba beans, due to their favourable growing conditions in the UK and the sustainable nutritional enhancement they provide.

    Despite being an excellent alternative to the ubiquitous imported soya bean, used currently in bread as an improver, the great majority of faba beans grown in the UK go to animal feed at present.

    Researchers are optimising the sustainability and nutritional quality of beans grown here, with a view to encouraging farmers to switch some wheat producing land to faba bean for human consumption.

    Faba beans are particularly high in easily digested protein, fibre, and iron, nutrients that can be low in UK diets. But the majority of people are not used to cooking and eating faba beans, which poses a major challenge.

    Professor Julie Lovegrove is leading the ‘Raising the Pulse’ research programme. She said: “We had to think laterally: What do most people eat and how can we improve their nutrition without them having to change their diets? The obvious answer is bread!

    “96% of people in the UK eat bread, and 90% of that is white bread, which in most cases contains soya. We’ve already performed some experiments and found that faba bean flour can directly replace imported soya flour and some of the wheat flour, which is low in nutrients. We can not only grow the faba beans here, but also produce and test the faba bean-rich bread, with improved nutritional quality.”

    ‘Raising the Pulse’ is a multidisciplinary programme of research, funded by the UKRI Biotechnology and Biological Sciences Research Council, as part of their ‘Transforming UK Food Systems’ initiative.

    As well as consulting and working with members of disadvantaged communities, there will be studies using our novel foods at the University of Reading’s students halls of residence and catering outlets.

    This links ‘Raising the Pulse’ with Matt Tebbit, who runs the University’s catering service and leads the University’s ‘Menus for Change’ research programme. He said: “Students will be asked to rate products made or enriched with faba bean, such as bread, flat bread, and hummus. They will be asked questions about how full they felt, for how long and their liking of the foods. It is hoped that faba bean will improve satiety, as well as providing enhanced nutritional benefits in products that are enjoyable to eat.”

    Before there are products to be tested, the beans must be grown, harvested and milled. ‘Raising the Pulse’ seeks to improve these stages as well. Researchers will be choosing or breeding varieties that are healthful as well as high yielding, working with the soil to improve yield via nitrogen fixing bacteria, mitigating environmental impacts of farming faba beans, planning for the changing climate, and more.

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    University of Reading

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  • Turning a poison into food

    Turning a poison into food

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    Newswise — Methanogens are microorganisms that produce methane when little or no oxygen is present in their surroundings. Their methane production – for example in the digestive tract of ruminants – is relevant for global carbon cycling, as methane is a very potent greenhouse gas, but can also be used as an energy source to heat our houses.

    A toxic base for growth

    The object of the study now published in Nature Chemical Biology are two marine heat-loving methanogens: Methanothermococcus thermolithotrophicus (lives in geothermally heated sediments at around 65 °C) and Methanocaldococcus jannaschii (prefers deep-sea volcanos with around 85 °C). They obtain their cellular energy by producing methane and receive sulfur for growth in form of sulfide, that is present in their environments.  While sulfide is a poison for most organisms, it is essential for methanogens and they can tolerate even high concentrations of it. However, their Achilles’ heel is the toxic and reactive sulfur compound sulfite, which destroys the enzyme needed to make methane. In their environments, both investigated organisms are occasionally exposed to sulfite, for example, when oxygen enters and reacts with the reduced sulfide. Its partial oxidation results in the formation of sulfite, and thus the methanogens need to protect themselves. But how can they do this?

    A molecular snapshot of the process

    Marion Jespersen and Tristan Wagner from the Max Planck Institute for Marine Microbiology in Bremen, Germany, together with Antonio Pierik from the University of Kaiserslautern, now provide a snapshot of the enzyme detoxifying the sulfite. This butterfly-shaped enzyme ist known as the F420-dependent sulfite reductase or Fsr. It is capable of turning sulfite into sulfide – a safe source of sulfur that the methanogens require for growth. In the current study, Jespersen and her colleagues describe how the enzyme works. “The enzyme traps the sulfite and directly reduces it to sulfide, which can be incorporated, for example, into amino acids”, Jespersen explains (see figure). “As a result, the methanogen doesn’t get poisoned and even uses the product as its sulfur source. They turn poison into food!”

    It sounds simple. But in fact, Jespersen and her colleagues found that they were dealing with a fascinating and complicated overlap. “There are two ways of sulfite reduction: dissimilatory and assimilatory”, Jespersen explains. “The organism under study uses an enzyme that is built like a dissimilatory one, but it uses an assimilatory mechanism. It combines the best of both worlds, one could say, at least for its living conditions.”

    It is assumed that the enzymes from both the dissimilatory and the assimilatory pathway have evolved from one common ancestor. “Sulfite reductases are ancient enzymes that have a major impact on the global sulfur and carbon cycles”, adds Tristan Wagner, head of the Max Planck Research Group Microbial Metabolism at the Max Planck Institute in Bremen. “Our enzyme, the Fsr, is probably a snapshot of this ancient primordial enzyme, an exciting look back in evolution.”

    Biotechnological applications in view

    The Fsr not only opens up evolutionary implications but also allows us to better understand the fascinating world of marine microbes. Methanogens that can grow only on sulfite circumvent the need to use the dangerous sulfide, their usual sulfur substrate. “This opens opportunities for safer biotechnological applications to study these important microorganisms. An optimal solution would be to find a methanogen that reduces sulfate, which is cheap, abundant, and a completely safe sulfur source”, says Wagner. In fact, this methanogen already exists, it is Methanothermococcus thermolithotrophicus. The researchers hypothesized that Fsr orchestrates the last reaction of this sulfate reduction pathway, because one of its intermediates would be sulfite. “Our next challenge is to understand how it can transform sulfate to sulfite, to get a complete picture of the capabilities of these miracle microbes.”

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    Max Planck Institute for Marine Microbiology

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  • What Biotechnology’s Paradigm Shift Means for Businesses

    What Biotechnology’s Paradigm Shift Means for Businesses

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    Opinions expressed by Entrepreneur contributors are their own.

    The past three years have changed nearly every industry. Where business used to be conducted in person, in offices and laboratories, the coronavirus pandemic forced a change. When remote work became mandatory, even traditional industries like the biopharmaceutical sector had to embrace new technologies.

    Today, the world may no longer be required to isolate and keep a distance, but the influence of advanced technologies is only growing. Their potential is apparent in shortening the time it takes to bring medications to market, dealing with supply chain issues and personalizing medicine.

    The paradigm shift of biopharma

    The biopharmaceutical industry has a reputation for being rather traditional. Despite its dependence on research, development and innovation, the industry has relied on tried and tested ways of conducting research. Conducting clinical trials and bringing new medications to the market tended to follow a specific format. This traditional business model has helped biopharma in the U.S. become a global leader for decades.

    Although emerging countries have been mounting a challenge, the United States continues to dominate the global pharmaceutical market. Five of the top ten pharmaceutical companies worldwide are based in this country. Their sales account for nearly 50% of all sales of medication around the world.

    2020 turned the industry on its head. As governments decided to impose lockdowns on their citizens, countless clinical trials came to an abrupt halt. Other companies rechanneled their energies into developing Covid-19 vaccines; for one of those companies, Pfizer, the vaccine resulted in the business becoming number one in the U.S.

    Others again started to look at advanced technologies to transform their operations. This is how artificial intelligence (AI) and machine learning (ML) entered this field. Initial results of AI and ML developments are exciting and have ensured that these technologies are here to stay for the foreseeable future.

    Related: The Future of Food: How Biotech Will Save Us All

    Making medications available faster

    The biopharmaceutical industry has long faced questions about the time it takes to develop, test and deliver a new drug to the market. During the pandemic, the rapid development of mRNA vaccines showed that technology could accelerate the process safely. In addition, the Pfizer / BioNTech and Moderna vaccines also proved the viability of mRNA technology.

    Jan van de Winkel, President and CEO of Danish biotechnology company Genmab, believes that next-generation technologies will be the key to accelerating drug development. In this context, biopharmaceutical companies are starting to take advantage of the likes of AI and ML. AI can process and analyze larger data volumes than humans can. This enables scientists to recognize patterns and their implications faster than ever before.

    ML-based algorithms are being used successfully in clinical trials. One recent example of this is Anavex Life Sciences. The company’s drug candidate Anavex2-73 looks set to provide treatment for dementia patients. The drug is undergoing a phase 2a clinical trial with only 32 patients. Anavex has been using decentralized trials since before the pandemic, minimizing the need to travel and making trials more accessible for patients. The company is supplementing them with whole genome analysis to enhance trial results.

    Utilizing technology like this can help speed up the development of new drugs without compromising patient safety.

    Related: Orchestrating an Innovation Ecosystem

    Improving supply chains

    One of the pandemic’s most noticeable consequences was supply chain disruption. Like others, the biopharmaceutical industry scrambled to continue supplying life-changing medications. As manufacturing and shipping all but halted in countries with strict restrictions, biopharma manufacturers needed to look for alternatives.

    Establishing closer relationships with external contractors proved to be one of the solutions. Those contract manufacturing organizations (CMOs) have always been a part of the industry. But their role was often confined to early clinical development or filling in the odd production lot. Since 2020, CMOs have both cemented and extended their role in the biopharma industry. Currently, CRB survey results suggest that more than half of biopharma manufacturers plan to use these contractors as an integral part of their pipeline.

    Genmab found that working with CMOs added value to their manufacturing of modified antibody candidates and related products. External organizations were able to offer highly specialized services that supported in-house manufacturing.

    Personalizing medicine

    Precision medicine, or personalized medicine, holds the promise of customizing treatments for the individual. Backed by data, this approach would allow doctors to make recommendations based on the patient’s genetics and lifestyle. Precision medicine has huge potential in cancer treatment, for example.

    Experts also believe that precision medicine may hold the key to the continued growth of the entire sector. According to analysts from Boston Consulting Group, medicines driven by biomarkers derived from genomic data will be at the heart of this development. At the same time, the analysts highlight the challenges this type of medication brings. Personalizing treatments and drugs increases manufacturing complexity in ways that the industry is only just starting to explore.

    Related: How Green Pharma Can Cure Disease and (Possibly) Save the Planet

    Cooperating for patient benefit

    The biopharmaceutical industry is competitive. However, during the pandemic, cooperation between businesses became one of the drivers behind progress. Accelerating the time it took to develop, test, and distribute vaccines worldwide required manufacturers to streamline their processes. They also needed to work closely with regulators to ensure vaccines were both safe and effective before entering mainstream production.

    Some industry insiders refer to the pandemic years as a period of creativity. Key players in the industry were forced to change their approach to manufacturing and distribution. The entire sector came together to solve a global problem at an unprecedented scale. Larger manufacturers provided the capacity and infrastructure that small, innovative biotechnology outfits needed to bring their products to the public. The cooperation between Pfizer and BioNTech is perhaps the best-known example of this synergy.

    Biotechnology and the biopharmaceutical industry are starting to embrace technology to transform their research and development departments and manufacturing processes. Continuing this digital transformation will give patients faster access to life-saving treatments and, eventually, personalized pharmaceuticals.

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    Jessica Wong

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  • Wristwatch device gives therapists opportunity to guide PTSD patients through treatment

    Wristwatch device gives therapists opportunity to guide PTSD patients through treatment

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    Newswise — Sights, smells and sounds of everyday life can supply the triggers that take someone with PTSD right back to the scarring scene they’re trying to forget. 

    With PTSD, or post-traumatic stress disorder, a honking horn, a crowded coffeehouse or a sharp scent can bring back traumatic memories that can raise the heart rate, increase muscle tension and lead to anxiety and depression. These reactions occur even without the presence of danger, but they pose their own threat by causing strains on relationships at home and work, igniting the need to avoid certain situations and contributing to mood changes.

    PTSD can happen to anyone at any age, according to the National Institutes of Health, and treatment options include medications as well as therapy. Researchers at MUSC Health recently published a paper in the Journal of Psychiatric Research where they worked with medical device company Zeriscope to test a device called Bio Ware, which is designed to enhance the effects of prolonged exposure therapy, a common, evidence-based therapy for patients with PTSD.

    And with between 11 and 30% of veterans experiencing symptoms of PTSD, the research team looked at using Bio Ware with service members at the Ralph H. Johnson VA Medical Center specifically. 

    With in vivo exposures, which are a key component of prolonged exposure therapy, patients are tasked with putting themselves in safe but uncomfortable or triggering situations outside of their therapy sessions, as a form of homework. If they have a fear of crowded spaces, for example, their therapist may ask them to go to the grocery store at a busy time and then share their reaction at the next therapy session. If the service member is stressed by loud spaces and avoids them, their therapist may send them to a loud sporting event, for example, in an effort to help them learn to feel more comfortable in those situations and not have to avoid them in the future.  

    When done properly, in vivo exposures have proven successful and helpful to patients, but with so much relying on the patient and their interpretation of their own stressors, Sudie Back, Ph.D., a professor in the department of psychiatry at MUSC Health and principal investigator for the NIMH-funded study, sees room for error. 

    “What I find so exciting about this new Bio Ware device,” she said. “Is that when used alongside evidence-based, exposure treatment methods for PTSD, we’ve seen significantly better results for our patients.” Back and her team saw significant decreases in both PTSD symptoms and depression symptoms with their patients who used the new technology.

    As a wearable device, the Bio Ware system includes a discreet button-shaped camera attached to the patient’s clothing, a watch-sized tool around their wrist and a Bluetooth headphone in their ear so their therapists can be virtually with them in the experience or situation that causes them stress. The clinician can see immediate recordings of the patient’s heart rate, breathing and emotional distress, and they can guide them through the experience by either pushing them to do more or pulling them back to do less, to optimize the in vivo exposure.

    According to Back, “This is the first time, to my knowledge, that we’ve been able to virtually go with patients during their in vivo exposures and have instant access to their physiological data in the moment to really help them get the most out of those exercises, which I believe will translate into them seeing significant reductions in their PTSD symptoms.”

    Bill Harley, the co-founder and CEO of Zeriscope, compares it to working out on your own versus with a personal trainer.

    “Communicating with patients while simultaneously seeing their biophysics is incredibly helpful,” he said. “A lot of healing happens in the in vivo exposures, and Bio Ware enriches that experience.”

    The “special sauce” created with Bio Ware lies in the autonomic nervous system according to Robert Adams, M.D., the president and co-founder of Zeriscope and a professor of neurology at MUSC Health. Previously developed watches aimed for something similar, but they only collected pulse information. This system goes a level deeper, he says, by directly questioning the autonomic nervous system.

    The autonomic nervous system controls physiologic reactions like heart rate, blood pressure and breathing. By using the same technology used in lie detector tests, physicians can take this galvanic skin response, change the patient’s triggering experience accordingly and watch how the actions that they direct the patient to do impact the autonomic nervous system.

    One of these days, they know they gotta get goin’,

    Out of the door and down the street all alone.

    Adams thinks the line from the Grateful Dead song “Truckin’” summarizes the need for Bio Ware. “It’s an expression of what exposure therapy really is. You’ve got to go back out into the real world on your own, but we can help.”

     

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    About MUSC

    Founded in 1824 in Charleston, MUSC is the state’s only comprehensive academic health system, with a unique mission to preserve and optimize human life in South Carolina through education, research and patient care. Each year, MUSC educates more than 3,000 students in six colleges – Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy – and trains more than 850 residents and fellows in its health system. MUSC brought in more than $327.6 million in research funds in fiscal year 2021, leading the state overall in research funding. MUSC also leads the state in federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.

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    Medical University of South Carolina

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