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Category Archives: BioEngineering

Rapid Breath Test for COVID-19 Developed in Dallas – NBC 5 Dallas-Fort Worth

Researchers at the University of Texas at Dallas have developed a sensor that could detect a COVID-19 infection from your breath.

The portable, reusable breath test device, designed to provide results in less than 30 seconds, is being developed by Dallas-based SOTECH Health, which licensed the sensor technology developed by Dr. Shalini Prasad, department head and professor of bioengineering in the Erik Jonsson School of Engineering and Computer Science.

The device detects chemical markers of the bodys response to the virus.

It is not a diagnostic test for COVID, instead would be used as a screening tool and followed up with diagnostic testing, like a molecular PCR test.

The latest news from around North Texas.

"This test is revolutionary and paradigm shifting primarily because it is looking for human body's response or host response to the coronavirus," said Prasad.

SOTECH'S founding CEO Craig Micklich says the device could be used as a screening tool at places like large entertainment venues, airlines and ballparks.

"The value of the device is actually the high throughput of finding negative individuals, to push them through, to be able to get on airlines get in venues, any kind of venue," said Micklich.

SOTECH has already applied for FDA emergency authorization now it waits to see if the COVID-19 breath analyzer will become the next weapon in ending the pandemic.

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Boosting the body’s response to infections with a bio-inspired peptide – EurekAlert

image:Justin Schaal, PhD, assistant professor of research pathology at the Keck School of Medicine of USC view more

Credit: USC photo/ Ricardo Carrasco III

Somewhere along the long and winding road of evolution, our ancestors lost the ability to produce a small but mighty group of molecules called theta-defensins that help fight bacterial infections.

More than seven million years later, researchers at the Keck School of Medicine of USC are creating new-and-improved versions of these molecules as a potential way to treat antibiotic resistant superbugs.

The research, just published in Scientific Reports, was led by Justin Schaal, PhD,an assistant professor of research pathology at the Keck School of Medicine. The paper describes the development of a new, bio-inspired molecule that is highly effective in clearing bacterial infections in an animal model. Importantly, the molecule does not act as an antibiotic, but rather as an immune stimulant, representing a new way to treat life-threatening antibiotic resistant infections.

The need for alternatives to antibiotics

Since their introduction more than 70 years ago, antibiotics have been the standard of care for bacterial infections. Despite dozens of varieties, almost all work by killing bacteria directly or by blocking their ability to proliferate.

This is the root cause of antibiotic resistance, Schaal said. Bacteria have an immense ability to evolve rapidly, which gives them power to overcome direct-acting antibiotic molecules.

Over the past two decades, an increasing number of bacteria have become resistant to all but the most powerful antibiotics. Several groups of such superbugs exist, including Carbapenem-resistant Enterobacteriaceae (CRE). CRE, which include certain strains ofE. coliandKlebsiella pneumoniae, are resistant to the class of antibiotics known as carbapenemsa last resort option for many patients with persistent infections. According to the Centers for Disease Control and Prevention, in the U.S. alone, CRE superbugs represent an increasing fraction of the more than 140,000 deadly or life-threatening infections caused by species of Enterobacteriaceae.

To address this urgent threat to human health, the National Institutes of Health (NIH) challenged researchers to find new strategies to combat antibiotic resistant bacteria. Building on pioneering research on theta-defensins led by Michael Selsted, MD, PhD, chair and professor of pathology, Schaal and his colleagues got to work.

Bioengineering molecules to work like theta-defensins

Using as inspiration RTD-1, a naturally occurring theta-defensin found in old-world monkeys such as baboons and rhesus monkeys, the researchers bioengineered similar molecules and screened them for their ability to fight Klebsiella infections in a mouse model. The most potent peptide they created, a highly stable cyclic peptide called MTD12813, is 10 times more efficient than RTD-1 in clearing infections.

While more work is needed to determine exactly how MTD12813 works, the researchers know it activates the immune systemspecifically cells called macrophages and neutrophils that engulf and destroy pathogens. The peptide also modulates the immune response, reducing poorly regulated inflammation that often occurs when the body fights a bacterial infection.

We call this peptide a host-directed anti-infective because rather than kill the bacteria directly like traditional antibiotics, it stimulates the hostusto fight the infection, Schaal said.

Through a licensing agreement with USC, the technology will now be developed further in partnership withOryn Therapeutics.

Based on this and related research conducted at USC, Oryn is developing a novel class of macrocyclic peptides as therapeutics for unmet needs in autoimmune and inflammatory diseases, infectious diseases, and cancer. We are quite optimistic about the prospects for turning the important scientific advances reported in this publication into successful treatments for increasingly dangerous bacterial infections, said Robert Erwin, Oryns Chief Executive Officer.

Selsted said the timing for the development of this technology is right, given current concerns that the next pandemic may be bacterial in nature.

This new discovery of how to stimulate host clearance of bacteria is really timely, he said.

About the study

The title of the paper is A host-directed macrocyclic peptide therapeutic for MDR gram-negative bacterial infections. Additional authors are Yoshihiro Eriguchi, Dat Q. Tran, Patti A. Tran, Chase Hawes, Anthony E. Cabebe, Kaitlyn Pike, Katie Trinh, and Andr J. Ouellette, all from the Keck School of Medicine of USC.

The work was supported by grants from the National Institutes of Allergy and Infectious Diseases (RO1 AI22931, R01 AI125141), the National Institute of Dental and Craniofacial Research (R01DE021341), the Southern California Clinical and Translational Science Institute (UL1 TR000130 ), and the National Cancer Institute (P30 CA014089).

About Keck School of Medicine

Founded in 1885,theKeck School of Medicine of USCis one of the nations leading medical institutions, known forinnovative patient care, scientific discovery, education and community service. Medical and graduate students work closely with world-renowned faculty and receive hands-on training in one of the nations most diverse communities. They participate in cutting-edge research as they develop into tomorrows health leaders. With 1200 resident physicians across 70 specialty and subspecialty programs, the Keck School is the largest educator of physicians practicing in Southern California.

Scientific Reports

Experimental study

Animals

A host-directed macrocyclic peptide therapeutic for MDR gram-negative bacterial infections

6-Dec-2021

Selsted is a co-founder and Chief Scientific Officer of Oryn Therapeutics, LLC (Oryn). He is an equity holder but receives no income from Oryn. Tran is the Scientific Director of Oryn and is an equity holder. Ouellette is an equity holder in Oryn but receives no income. Oryn has licensed technology described in this publication from the University of Southern California and the relationship between Oryn and USC is disclosed to and approved by all parties. All other authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Prescient Therapeutics bolsters scientific advisory board with CAR-T and bioengineering experts – Small Caps

Clinical stage oncology company Prescient Therapeutics (ASX: PTX) has made plans to advance and accelerate its proprietary OmniCAR platform after unveiling two high-profile additions to its scientific advisory board.

In a statement to the market, the oncology company said it had appointed physician-scientist, Dr Marco Davila from the Moffitt Cancer Center and bioengineering expert Professor Andrew Tsourkas from the University of Pennsylvania, effective immediately.

The dual appointments are expected to bring unsurpassed expertise to Prescients ongoing development work on CAR-T therapies and binder protein engineering.

The company explained the rationale behind the move by stating that Dr Davila and Professor Tsourkas would bring deep complementary expertise to its operations and would compliment an existing team of highly credentialed personnel on the scientific board.

Currently, the broader team is comprised of CAR-T expert Professor Phil Darcy, hematologist and CAR-T researcher Professor H. Miles Prince and brain cancer specialist and cell therapy researcher Professor Don ORourke.

As a highly experienced clinical developer of CAR-T, Dr Davila is currently regarded as a leading figure in the field and is often invited to address global oncology conferences.

Dr Davila currently works at the Department of Blood and Marrow Transplantation at the Moffitt Cancer Center one of the largest cancer centres in the US treating patients with hematologic malignancies with various cell therapies.

Dr Davilas current research includes pre-clinical development and clinical translation of gene-engineered cell therapies, including CAR-T therapies, for patients with hematologic and solid tumour malignancies.

Moreover, Dr Davilas research has received widespread acclaim including generous grants and awards from the American Society of Hematology, Damon Runyon Cancer Research Foundation, the American Society of Clinical Oncology and the American Society for Clinical Investigation, respectively.

From my clinical experience with CAR-T therapies, as well as their pre-clinical development, I have seen both the early success of this revolutionary therapy in B cell malignancies and also the challenges in translating it to other cancers, said Dr Davila.

I am excited by the capabilities of OmniCAR to overcome many of these obstacles and bring gene-engineered cell therapies to many more patients. I am delighted to be appointed to Prescients SAB to help guide the development of OmniCAR, he added.

According to Prescient Therapeutics, OmniCAR is a universal immune receptor platform enabling controllable T-cell activity and multi-antigen targeting with a single cell product.

The company says it is the first of its kind: the first universal immune receptor allowing post-translational covalent loading of binders to T-cells.

As well as the addition of Dr Davila to its scientific board to help advance OmniCAR, Prescient is also bolstering its ranks from the University of Pennsylvania and an original co-founder of the technology.

Professor Tsourkas is a co-inventor of the patents developed at Penn and licensed by Prescient to form OmniCAR.

OmniCAR is based on technology first licensed from Penn as well as the so-called SpyTag/SpyCatcher binding system licensed from Oxford University. Given OmniCARs development path and close collaboration with Penns researchers, Prescient acquired the services of Professor Tsourkas as an organic fit.

Professor Tsourkas particular expertise in the conjugation of proteins is especially relevant to the development of OmniCARs binders, which involves incorporating SpyTag into antibodies and other antigen-binding molecules, the company said.

It has been wonderful to see the rapid progress of development of OmniCAR since Prescient licensed the underlying patent from Penn last year, said Professor Tsourkas.

The rapid, covalent nature of OmniCARs binding confers many unique capabilities and advantages over conventional CAR-T approaches. I look forward to assisting Prescient in the development of OmniCAR and its associated binders to address a variety of different cancers, Professor Tsourkas added.

Over the next 12 months, Prescient expects to expand the cohort read-out for its PTX-100 drug, as well as complete enrolment in the expansion cohort by Q3 2022. Prescient is confident of announcing several further value-adding milestones for each OmniCAR program throughout 2022.

In addition, Prescient has confirmed it expects to receive results for its PTX-200 Ph1b AML trial early next year with several cell therapy enhancements expected to come out of stealth mode in the first half of 2022.

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Saving the world with synthetic biology – Scope – Scope

Drew Endy, PhD, a Stanford bioengineer, is the kind of brilliant that makes your head spin. His ideas come at a mile a minute, each one a potential mini revolution of standard biology, and his excitement for his work is palpable. But, to me, the best part about Endy is his drive to see a mega-mission through: to use bioengineering to change the world for the better, making contentious efforts to innovate with an eye toward solving social, humanitarian and environmental challenges.

In one of my latest Stanford Medicine magazine stories, "How synthetic biology could save us," I speak to Endy about his lofty vision and the research he's conducting to see it through.

If you ask Endy, synthetic biology is a field that aims to "make the making of things" easier. It's a type of science that expands beyond the natural world, creating tools and techniques to support the development of new biology-based innovations -- like new forms of medicine, or an altered crop that can fight pests on its own.

"We tend to think of biology as something that happens to us," Endy said in the story. "But more and more, we are happening to biology. We're in an era, scientifically, where we can express our intentions into the very kernel of life to allow for possibilities that are simply never going to exist otherwise."

One of Endy's big projects is something he calls "the cleanome," a concept rooted in genetics, but with a twist: In a cleanome, all of an organism's non-crucial genetic elements are removed. (Every living thing contains fundamental genes that support its life, in addition to stretches of DNA that are, essentially, garbage.) The goal is to remove genetic fluff, leaving only the core components that allow an organism to survive.

As Endy said in the story:

If you want to build an organism, you want to definitively know what you're working with, and right now part of what bioengineers are working with is ambiguity."

What bioengineering really needs, according to Endy, is certainty as to which genes are needed for a particular organism to survive along with what each gene is doing. ... Establishing a cleanome for key organisms would allow bioengineers to build and create with more certainty and safety, he said.

Endy and the researchers in his lab have other big ideas percolating too, one of which he's dubbed a "fail-safe" -- basically a built-in self destruct button for an engineered organism. Say, for instance, a scientist creates a type of cancer-fighting cell that runs around the body and gobbles up tumor cells. If that cell started to evolve new cell-gobbling abilities, that would be dangerous. A fail-safe construct built into the cell would notice such a change and kill the rogue cell before it kills its healthy neighbors.

During our interviews, I reflected on the enormity of his proposal: A civilization that not only coexists with bioengineering but also depends on it, harnesses it, continually develops it -- even loves it.

"You'd almost have to be some sort of benevolent dictator to truly see it through," I'd joked to him. He sees it a little differently. "Perhaps more like reluctant philosopher king."

Image by David Plunkert

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Collaboration aims to shrink the urban-rural divide and address the impact of climate change through student research network – EurekAlert

ST. LOUIS, MO, November 18, 2021 Just as there often exists an urban-rural divide in political and environmental landscapes, urban and rural education systems share the common issue of being under-resourced, especially for science education. As climate change looms over rural agricultural communities, urban heat islands could serve as critical partners for anticipating the future of economically important crops. Kristine Callis Duehl, PhD, the Sally and Derick Driemeyer Director of Education Research and Outreach at the Donald Danforth Plant Science Center and her collaborators at the Jackie Joyner Kersee Foundation and University of Illinois Extension were awarded a three year, $685,000 grant from United States Department of Agriculture to create a synergistic partnership between urban and rural communities in Southern IL to establish a cross-regional curriculum that introduces bioengineering and plant monitoring technology to middle school aged youth in summer programs.

Young people at the Jackie Joyner-Kersee Foundation in East St. Louis, IL and at the Illinois Extension program in Waterloo, IL will monitor corn growth in both regions by using in-demand technology including drones and a microclimate field monitoring system developed by Danforth Center scientist Nadia Shakoor, PhD. By growing and comparing sweet corn, GMO commodity corn, and non-GMO commodity corn, students will see first-hand how bioengineering improves plant health and crop yield. By conducting joint fieldwork and presenting their ideas at a mini-conference, urban and rural youth will establish a collaboration that generates culturally mindful activities as well as authentic data that can help shed light on the impact of climate change on corn harvests. This collaboration will allow rural students to experience FarmBot robotics at work in smaller, urban plots and allow urban students to experience the use of drones used in precision agriculture on larger, rural farms. Ultimately, through this informal authentic research experience, participants will help develop a culturally informed curriculum that can be launched nationwide to establish a network of urban-rural authentic research hubs for non-formal summer programs.

Young people participating in the project will gain an understanding of gene editing and hands-on experience using robotics to plant corn, as well as experience using drone and microclimate monitoring systems to assess corn growth and the microclimate, said Callis-Duehl. It will also provide technological training, and exposure to data analysis to prepare them for the future, as big data analysis has become increasingly critical in agricultural science.

Youth will also gain leadership experience by providing feedback on curriculum so that it evolves and by teaching the youth the partner program how to use the agricultural technology unique to their research area (urban or rural).

Co-Project Directors include Lisa Walsh, Danforth Plant Science Center, Mark Fryer, Jackie Joyner Kersee Foundation and Amy Cope, University of Illinois Extension.

About the Donald Danforth Plant Science CenterFounded in 1998, the Donald Danforth Plant Science Center is a not-for-profit research institute with a mission to improve the human condition through plant science. Research, education, and outreach aim to have impact at the nexus of food security and the environment and position the St. Louis region as a world center for plant science. The Centers work is funded through competitive grants from many sources, including the National Science Foundation, National Institutes of Health, U.S. Department of Energy, U.S. Agency for International Development, U.S. Department of Agriculture and the Bill & Melinda Gates Foundation. Follow us on Twitter at @DanforthCenter.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Creating dangerous viruses in the lab is a bad way to guard against future pandemics – Bulletin of the Atomic Scientists

USAID animal disease surveillance work in Asia. Credit: Richard Nyberg / USAID. Credit: CC BY-NC 2.0.

In 2011, three top US government scientists penned an opinion piece in The Washington Post arguing why research modifying highly pathogenic avian influenza (H5N1) was a worthy undertaking. At the time, the National Institutes of Health (NIH) was facing blowback over having funded experiments that modified the virus to be transmissible among ferrets. The scientists argued that eliciting potentially dangerous mutations in the virus was necessary to protect humanity, should those mutations evolve naturally.

We cannot predict whether or not something will arise naturally, nor when or where it might appear. Given these uncertainties, important information and insights can come from generating a potentially dangerous virus in the laboratory, wrote Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases, Francis Collins, the head of NIH, and Gary Nabel, then a top official at Faucis institute.

Amid the controversy generated by this influenza research, the US government implemented a pause on federal funding in 2014 for selected research reasonably anticipated to increase transmissibility or pathogenicity of influenza, SARS, and MERS viruses. These were experiments that fell within a subset of scientific study called gain-of-function research. In 2017, the government lifted the pause and put in place a requirement that the US Department of Health and Human Services conduct a risk-benefit assessment on research that could confer these attributes to potential pandemic pathogens.

The federal government continues to fund such experimentation, but, as scientists, media, and online sleuths have delved into the origins of COVID-19, they have revealed weaknesses in past and current government oversight of projects modifying viruses. The revelations have underscored the degree to which gain-of-function research in the name of predicting pandemics is an idea that doesnt seem to fade.

US-funded coronavirus bioengineering. In 2018, EcoHealth Alliance, a US-based nonprofit research organization, submitted a grant proposal to the Defense Advanced Research Projects Agency (DARPA) called DEFUSE: Defusing the Threat of Bat-borne Coronaviruses asking for over $14 million for a three-and-a-half year project to, as the name suggests, prevent a bat coronavirus from spilling over into people and seeding an outbreak. The team would study viral evolution and spillover risk[s] of SARS-related bat coronaviruses by collecting viruses from caves in Yunnan, China and doing experiments that included testing hybrid, lab-created bat coronaviruses on mice engineered to have human receptors.

One eye popping segment in the 2018 EcoHealth proposal to DARPA dealt with finding so-called furin cleavage sites. In SARS-CoV-2, the virus that causes COVID-19, a furin cleavage site allows its spike protein to be cut by the furin enzyme present in human airway tissues, making the virus better able to infect cells than others without the feature. The furin cleavage site represents a crucial difference between the COVID-19 virus and its relatives, including SARS-CoV, the virus responsible for the 2003 outbreak of that respiratory disease.

The process by which viruses hijack the cellular machinery of their hosts to reproduce themselves is sloppy, and the viruses that a cell produces arent always identical to the ones that infected the cell to begin with. This sloppiness helps the virus to evolve and adapt to new hostssuch as us. The furin cleavage site in SARS-CoV-2 could have evolved in this way.

Some proponents of the idea that the pandemic began with a lab accident in Wuhan, however, wonder whether the furin cleavage sites presence in the COVID-19 virus is simply a mark of natural viral evolutionan artifact of sloppy viral reproductionor rather is something else entirely: a sign of human bioengineering.

DARPA did not approve EcoHealths 2018 proposal, and its unknown whether the project received other funding. But the EcoHealth proposal, like another of the organizations collaborations with the Wuhan Institute of Virology that did get government funding, show the enduring interest scientists have in modifying viruses in the name of predicting pandemic pathogens. (NIH officials have denied that EcoHealths NIH-funded research is gain of function research, although NIH documents show that the organization failed to adhere to terms related to enhanced viral growth in its hybrid bat coronavirus studies. There is significant debate on what the definition of a dangerous gain-of-function experiment is.)

Predicting pandemics through gain-of-function research. An overarching goal of EcoHealths workas documented in the DARPA proposal and in other projectswas to learn which viruses were poised to spill over, in other words, to predict pandemics. Predicting how and when the next pandemic could arise is important, but tampering with viruses to do so is the wrong way to go about it. Predicting pandemics isnt like predicting the weather.

Weather prediction is a purely observational exercise. We have satellites and other tools to track weather to predict hurricanes. The forecast process begins with observations. Scientists use this data to develop hurricane forecast models. Geophysical fluid dynamics are well understood, based on the laws of physics (i.e. density, flow velocity, pressure, and temperature) enabling scientists to develop atmospheric and climate models.

Scientists do not experiment on clouds to see if they can cause hurricanes.

In 2004, the National Academy of Sciences published its seminal report, Biotechnology Research in an Age of Terrorism. It listed seven experiments of concern that should not be done.

Bioengineering SARS-related coronaviruses in ways that could increase efficient infection of human cells and that increase viral load, pathogenicity, and lethality in mice genetically engineered to have respiratory cells with human features, i.e., humanized mice, as NIH documents show was done by EcoHealth Alliance and its Wuhan partners, would conceivably implicate points 3, 4, and 5 of the 2004 report. Whether the Wuhan experimentation was gain of function is a matter of debate, but some scientists disagree with NIHs assessment that it wasnt.

Ideally, Congress should hold a hearing to debate what kind of research should not be done and do more to investigate the origins of the pandemic. Certainly, there have been calls to do so.

There are other less risky ways of preventing pandemics than conducting gain-of-function research on pathogens. Many pathogens capable of causing human outbreaks originate in animals, and surveillance of wild and domestic animals for signs of illness makes sense. This is the One Health approach. With One Health, the goal is to prevent the spread of deadly zoonotic microbes into humans through improved communication and collaboration between human and veterinary medicine.

Preventing pandemics through rapid identification and response is an important goal; the One Health approach that emphasizes animal and human health and disease surveillance is the key to doing this, not risky gain-of-function research.

Authors note: Many thanks to Richard Ebright, Board of Governors Professor of Chemistry and Chemical Biology, Waksman Institute, Rutgers University for his invaluable comments and links to technical references.

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