Posts tagged with "science news"

Mars illustrated by Mina Tocalini for 360 MAGAZINE.

Water Infrastructure Funding Act

The California Legislative Analysts Office has just produced a report to estimate the financial impact of the “Water Infrastructure Funding Act of 2022,” a proposed ballot initiative that aims to increase the annual supply of water to Californians by five million acre feet. The contents of this report are good news for every Californian. More water. Lower water bills.

The initiative calls for two percent of the state general fund to be set aside to develop new water supplies. Projects eligible for this funding would include the development or expansion of facilities for:

  • Groundwater cleanup and storage.
  • Stormwater capture, treatment, and storage.
  • Water recycling.
  • Surface reservoirs.
  • Desalination of seawater or brackish water.
  • Water conveyance, such as canals or pipes.

Also eligible for funding are water conservation programs to achieve up to 1 million acre-feet of the total objective of 5 million acre-feet of water.

Among the fiscal effects predicted by the Legislative Analyst include increased state spending on water supply projects, and potentially less funding available for other state activities. Notwithstanding the multi-billion budget surplus California’s legislature currently enjoys, this redirecting of spending for water projects is what the initiative proponents intend. The State of California has neglected its water infrastructure for decades. With climate change promising dryer winters and a reduced Sierra snowpack, this is the perfect moment for California to prioritize spending on a resilient water infrastructure.

Assemblyman Devon Mathis (R, Tulare), a supporter of the initiative who has gathered endorsements from a growing bipartisan list of state legislators, had this to say in response to the LAO report: “This is a first of its kind ballot initiative. We set the goal based on our state’s current and future water needs, set ongoing funding for a diverse set of eligible project categories, and placed a sunset for when the goal is reached.” Mathis added, “This is a vote for people to lower their water bills, and for cities and school districts to upgrade their water systems without breaking their local budgets.”

Mathis is correct. As the LAO report notes, “it could result in water customers paying lower water bills than they otherwise would in the absence of the measure.”

One of the proponents, Lisa Ohlund, the retired general manager of the East Orange County Water District, explained the long-term benefits of this initiative, saying “climate change projections have many water districts concerned about their ability to reliably deliver safe water in quantities that will protect people, trees and the economy. This initiative focuses tax dollars on this enormously important problem at a pivotal time. We must take action to prepare for the increasingly harsh storms that will dump large amounts of rain on California, and the extended dry periods where we must look to water recycling and desalination to help fill in the shortfalls. California lead the world in water in the last century; we need to do the same in this one.”

To learn more about the progress of this game changing initiative, visit their website HERE.

Art by Mina Tocalini for use by 360 Magazine

Scientists Mapping Next Pandemic

An international team of scientists has created a powerful new resource to speed the development of vaccines and treatments to battle the next pandemic.

University of Virginia School of Medicine researcher Wladek Minor, PhD, and collaborators in China and Poland have developed an Internet information system, called virusMED, that lays out all we know about the atomic structure and potential vulnerabilities of more than 800 virus strains from 75 different virus families, including SARS-CoV-2, influenza, Ebola and HIV‑1. Several of the collaborators, including the lead investigator, Heping Zheng, are former students and members of Minor’s lab at UVA. 

This new panorama of the proteins of potential threats will help scientists respond quickly and effectively against the next pathogen poised to wreak havoc on humanity. Minor and his collaborators compare the resource to Google Maps, in that it organizes and annotates major points of interest on a virus that scientists can use as a roadmap in drug and vaccine development.

“The battle with COVID-19 is not over yet, but we cannot wait to start preparing for the next pandemic. VirusMED is a step towards an advanced information system that brings together researchers with diverse expertise to tackle complex biomedical challenges,” said Minor, the Harrison Distinguished Professor of Molecular Physiology and Biological Physics at UVA. “The information contained in virusMED will help viral researchers from many disciplines, especially those working on drug design or anti-viral therapies. We provide novel structural analysis and integrate pertinent information from various resources to provide a comprehensive picture of the proteins’ most important and vulnerable regions.”

Virus Hotspots

By quickly unlocking the SARS-CoV-2 virus mechanism of action, scientists were able to develop safe and effective vaccines for COVID-19. Minor’s new database aims to put that type of critical information at scientists’ fingertips in one convenient location.

VirusMED contains extensive information on virus species and strains, hosts, viral proteins and antibodies, as well as drugs that have already been approved by the U.S. Food and Drug Administration, among other important scientific data. The researchers call the points of interest on a virus its “hotspots,” and these hotspots make for strong starting points for drug and vaccine development.

“One of the most promising strain-indifferent antibody therapies developed for the treatment of COVID-19 used this type of information to improve upon a unique antibody isolated from a survivor who was infected by the SARS virus back in 2003,” said David Cooper, PhD, research faculty in Minor’s lab. “People who are surprised by rapid drug and vaccine design don’t realize that researchers today are building upon decades of previous research.”

One of virusMED’s major advantages is that it brings together the extant knowledge about viruses in one location, Minor said. Previously, that data was spread across multiple resources and often “siloed” so that it was not easily accessible. With virusMED, researchers can browse the information by virus or by their hotspot of interest.

The free and accessible database can be found HERE.

“One of the goals of my lab is to make tools that other scientists can use. We look at the forest and find ways to help others focus on the trees,” Minor said. “Resource generation is not glamorous, but the ultimate goal of science is to make life better. One of the anonymous peer-reviewers of the paper claimed they instantly became an enthusiastic user of the system. We expect virusMED to really make a difference.”

Findings Published

The researchers have published their findings in the scientific IUCr Journal. The work will be featured on the journal’s cover. The research team consisted of HuiHui Zhang, Pei Chen, Haojie Ma, Magdalena Woinska, Dejian Liu, Cooper, Guo Peng, Yousong Peng, Lei Deng, Minor and Zheng. .

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Image of Telescope via Gabrielle Archulleta for Use by 360 Magazine

New Report Underlines Importance of Science and Tech Funding

Investments in science and technology research are vital to the United States’ economic growth and global leadership, according to a new report from Rice University’s Baker Institute for Public Policy.

The Biden administration has made science and technology (S&T) a centerpiece of its early policy agenda with ambitious targets for federal investments in research and development (R&D). There are also growing concerns in Congress about the United States’ global leadership in S&T-focused industries, especially in relation to China.

“As the high technology sector (e.g., advanced computing and communications, social media platforms and other web-based services) becomes an increasingly large part of the overall U.S. economy, federal funding for early stage R&D, which has been at the root of much of the technological progress of this past century, is more important than ever,” wrote the Baker Institute’s Kenneth Evans, a scholar in science and technology policy, and Kirstin Matthews, a fellow in science and technology policy.

While President Biden’s first budget proposal aims to authorize historic increases to federal R&D agencies, the authors argue that significant challenges remain to ensure long-term, international competitiveness across scientific disciplines and advanced technologies.

According to their report, shifting priorities between administrations, changes to the ideology of Congress and broader economic conditions in the U.S. at large have resulted in inconsistent funding for R&D. 

“Traditionally, federal funding for R&D receives bipartisan support in Congress, particularly for health and defense-related research activities,” the authors wrote. “However, since the mid-1990s, government spending on basic research has declined or stagnated as a share of the U.S. GDP, in part due to the intrinsic uncertainties about the ultimate impacts of basic research.”

Science and technology R&D is essential to creating new knowledge and tools, the authors argue, because it ensures the development of new products and technologies that can drive domestic and global economies. Economists estimate innovations stemming from S&T accounted for more than 60% of economic growth over the last century. 

Yet scientists have placed relatively little value on evaluating and communicating the broader societal impacts of basic research to the public and especially to policymakers, the authors argue. The authors encourage researchers, especially academic scientists driven to action by anti-science rhetoric during the Trump administration, to continue to engage in public outreach during the Biden presidency. 

“Universities should encourage and incentivize avenues for public engagement through increased support of existing programs or funding new activities for interested faculty, postdocs, graduate students and research staff,” they wrote. 

“Building public support for R&D, strengthening trust in scientific institutions and expertise, and increasing scientists’ participation in decision-making related to S&T issues are critical to ensuring that scientific discoveries and innovation benefit the broader public and that increased investment in R&D serves the public interest,” they continued.

The report was a collaboration with two Rice undergraduate students and research interns in the science and technology policy program—Gabriella Hazan and Spoorthi Kamepalli.

Health via 360 Magazine for use by 360 Magazine

Rice Team Creates New Treatment for Diabetes

Rice University bioengineers are using 3D printing and smart biomaterials to create an insulin-producing implant for Type 1 diabetics.

 

The three-year project is a partnership between the laboratories of Omid Veiseh and Jordan Miller that’s supported by a grant from JDRF, the leading global funder of diabetes research. Veiseh and Miller will use insulin-producing beta cells made from human stem cells to create an implant that senses and regulates blood glucose levels by responding with the correct amount of insulin at a given time.

Veiseh, an assistant professor of bioengineering, has spent more than a decade developing biomaterials that protect implanted cell therapies from the immune system. Miller, an associate professor of bioengineering, has spent more than 15 years researching techniques to 3D print tissues with vasculature, or networks of blood vessels.

“If we really want to recapitulate what the pancreas normally does, we need vasculature,” Veiseh said. “And that’s the purpose of this grant with JDRF. The pancreas naturally has all these blood vessels, and cells are organized in particular ways in the pancreas. Jordan and I want to print in the same orientation that exists in nature.”

Type 1 diabetes is an autoimmune disease that causes the pancreas to stop producing insulin, the hormone that controls blood-sugar levels. About 1.6 million Americans live with Type 1 diabetes, and more than 100 cases are diagnosed each day. Type 1 diabetes can be managed with insulin injections. But balancing insulin intake with eating, exercise and other activities is difficult. Studies estimate that fewer than one-third of Type 1 diabetics in the U.S. consistently achieve target blood glucose levels.

Veiseh and Miller’s goal is to show their implants can properly regulate blood glucose levels of diabetic mice for at least six months. To do that, they’ll need to give their engineered beta cells the ability to respond to rapid changes in blood sugar levels.

“We must get implanted cells in close proximity to the bloodstream so beta cells can sense and respond quickly to changes in blood glucose,” Miller said. “We’re using a combination of pre-vascularization through advanced 3D bioprinting and host-mediated vascular remodeling to give each implant several shots at host integration.” 

The insulin-producing cells will be protected with a hydrogel formulation developed by Veiseh, who is also a Cancer Prevention and Research Institute of Texas Scholar. The hydrogel material, which has proven effective for encapsulating cell treatments in bead-sized spheres, has pores small enough to keep the cells inside from being attacked by the immune system but large enough to allow passage of nutrients and life-giving insulin.

“Blood vessels can go inside of them,” Veiseh said of the hydrogel compartments. “At the same time, we have our coating, our small molecules that prevent the body from rejecting the gel. So it should harmonize really well with the body.”

If the implant is too slow to respond to high or low blood sugar levels, the delay can produce a roller coaster-like effect, where insulin levels repeatedly rise and fall to dangerous levels.

“Addressing that delay is a huge problem in this field,” Veiseh said. “When you give the mouse, and ultimately a human, a glucose challenge that mimics eating a meal, how long does it take that information to reach our cells, and how quickly does the insulin come out?”

By incorporating blood vessels in their implant, he and Miller hope to allow their beta-cell tissues to behave in a way that more closely mimics the natural behavior of the pancreas.

Breaking News illustration via Nicole Salazar for use by 360 Magazine

Life on Jupiter

By: Skyler Johnson

A scientific study originally aimed at testing the capability of life on Venus has now shown that there is a chance for life not on our sister planet, but on the gaseous giant, Jupiter. 

The study aimed to figure out whether Venus could maintain life based on water activity, which is measured on a 0 to 1 scale, with 1 being pure water and 0 being the complete absence of it. The minimum viable water activity for life on Earth was determined to be 0.585, with Venus being 0.007, but Jupiter just reaching the threshold at 0.585. 

Jupiter is also the perfect temperature to maintain life, being -40 degrees F, which is just survivable. Life can only survive at that temperature and above. 

While these statistics may be exciting, you’re not exactly going to be seeing E.T. coming from Jupiter. After all, it’s a gaseous planet. Life, if any at all, would be existing within Jupiter’s clouds, and would only be made up of a single cell. The planet has a lot of Ultraviolet Radiation and very little nutrients, so sustaining life may not even be possible. Nevertheless, life is possible for the gaseous giant.

The scientific possibilities of this finding, while it may seem relatively minor given we don’t actually know if there’s life outside of planet Earth, it does offer some interesting possibilities. After all, we have no idea what these creatures may look like and what biological adaptations they may have in order to adapt to living in the dangerous conditions Jupiter provides. What we could end up finding might lead us to find ways to adapt as a species. 

Interestingly, if Jupiter ends up being inhabitable, there’s also a chance that one of Jupiter’s moons, Europa, houses life beneath it’s under-ice ocean, which would be similar to Earth’s Deep Ocean hydrothermal vents, which are basically a volcano erupting underwater and spouting out life-providing sediments. While we have no idea what’s under Europa’s surface there have been some calls for a probe so we may soon get some answers. 

Nevertheless, only time will tell what may be found on other planets. But with more information like with the study released today, who knows what the future may bring.

 

Image of Telescope via Gabrielle Archulleta for Use by 360 Magazine

Purdue Innovation Could Make Recycling More Profitable

By: Steve Martin

Hasler Ventures LLC plans to scale up to commercial levels a Purdue University patented technology that may accelerate the volume of waste plastic recycling.

The innovation is called Low-Pressure Hydrothermal Processing. It promises an economically and environmentally safe way to transform polyolefin plastic, the most common form of plastic, into gasoline, diesel fuel and other high-value items. Developed by Linda Wang, the Maxine Spencer Nichols Professor in the Davidson School of Chemical Engineering, the research was published in a 2021 issue of the peer-reviewed journal Fuel.

The United Nations estimates that more than 8 million tons of plastics flow into the oceans each year. Of all the plastics produced over the past 65 years (8.3 billion tons), about 12% have been incinerated and only 9% have been recycled. The remaining 79% have gone into landfills or the oceans. The World Economic Forum predicts that by 2050, the oceans will hold more plastic waste than fish if the waste continues to be dumped into bodies of water.

 “The key to solving this problem is to make it economically more attractive to collect and process the plastic waste stream into higher-value products at a significantly lower conversion cost,” said Dan Hasler, CEO of Hasler Ventures. “Current methods including incineration, pyrolysis and mechanical recycling have all proven to be ineffective or too costly, both financially and environmentally. They have not been able to draw the required private investment at a scale sufficient to divert the vast majority of the global 350 million tons of plastic waste produced annually from the landfill. We believe we can demonstrate first at pilot scale that hydrothermal processing is a less-expensive approach to produce fuels from plastic than from crude oil, making it a profitable venture to collect and process plastic, keeping it out of landfills and oceans.”

Purdue has put significant effort in this area for many years, said Mung Chiang, Purdue’s executive vice president for strategic initiatives and the John A. Edwardson Dean of the College of Engineering. “Solving this plastic waste problem will greatly benefit the environment and future generations,” Chiang said.

The recently invented conversion process incorporates hydrothermal liquefaction and efficient separation. Once the plastic is converted into oil or naphtha, it can be used as a feedstock for other chemicals or further separated into monomers, specialty solvents, or other products. The clean fuels derived from the polyolefin waste generated each year can satisfy 4% of the annual demand for gasoline or diesel fuels. Some results of Wang’s study were published in ACS Sustainable Chemistry and Engineering in 2019 and Fuel in 2020 and 2021. A video about the process is available online.

Hasler Ventures is collaborating with American Resources Corp. (NASDAQ:AREC) to use its Indiana-based chromatography pilot plant, currently in development, to demonstrate the technology.

Mark Jensen, president of American Resources Corp., said, “Once proven, the commercialized Purdue innovation could change perceptions about recycling plastics. We’re excited to support this environmentally critical project.”

Dolphin via Mina Tocalini for use by 360 Magazine

Venture Capital Funds Investing in Climate Change Innovation

Saving the planet from Climate Change devastation is one of the most important things we can do to date,  yet has often seen pushback from major investors who’ve focused their investments on safer industries like coal and oil. Luckily, there’s a growing trend of investment companies created for the purpose of saving the planet, promoting the idea that clean energy can benefit investors as well as our future, according to a new Venture Capital (VC) trend.

2021 has already seen multiple climate-focused fund launches. London-based One Planet Capital launched a fund for green tech, fintech, and sustainability-based B2C businesses, while actor Robert Downey Jr (Ironman, The Avengers) has founded FootPrint Coalition Ventures to invest in high-growth, sustainability-focused companies. European-based fund 2150 also launched this year, investing €200m ($240m) into start-ups developing sustainable technologies to lower carbon emissions in Europe’s cities. 

 The financial world used to think environmental issues couldn’t generate viable rewards, but another climate-focused fund, Congruent Ventures, believes a tipping point has been passed.

Congruent raises investment specifically for Climate Change solution start-ups and, with $300 million under management after closing its second fund at $175 million, managing partner and co-founder Abe Yokell said:

“If you brought up the word ‘cleantech’ to any institutional investor allocating to venture ten years ago, they would do their best to avoid the meeting, but now, there’s a fundamental belief that there will be significant financial returns investing broadly in climate tech over time.” 

Congruent’s portfolio includes electric vehicle charging provider Amply, which raised $13.2m last year from investors including Soros Fund Management and Siemens. Digitally controllable electrical panel company Span raised $20m in January through Congruent, with investors including Munich Re Ventures’ HSB Fund and Amazon’s Alexa Fund.

Congruent itself is well-founded, with investors including UC Investments, the Microsoft Climate Innovation Fund, Three Cairns Group, Jeremy and Hannelore Grantham Environmental Trust, and Surdna Foundation, among other institutions, foundations, and family offices.

Regulation A+ crowdfunding companies are also seeing investment, such as Digital Twins market leader Cityzenith, who recently launched their international ‘Clean Cities, Clean Future’ campaign as part of the Race to Zero movement.

Cities worldwide generate 70% of the world’s carbon emissions, but Cityzenith’s AI Digital Twin platform technology can help property asset management groups, city planners, and developers reduce emissions and move to carbon neutrality in the next ten years.

Cityzenith CEO Michael Jansen said at the launch of the ‘Clean Cities – Clean Future’ initiative: “We have to help the most polluted urban centers become carbon neutral, and we plan to do this by donating the company’s Digital Twin platform SmartWorldOS™ to key cities, one at a time, after every $1m we raise. We’re able to do this because of the recent surge of investment we’ve had as part of our $15m raise.”

Cityzenith is already benefiting from the funding shift, attracting $2.5m in investment since late 2020 through Regulation A+ crowdfunding and a surge in shares from $0.575 to $1.50 in just five months. The US company has raised $10m to date.

With a growing trend in climate change investment funds, hopefully we’ll be able to start decreasing carbon emissions and work towards saving the planet.

Chrons via Rice University News for use by 360 Magazine

New Bacteria to Help Detect Inflammatory Bowel Diseases

In an important step toward the clinical application of synthetic biology, Rice University researchers have engineered a bacterium with the necessary capabilities for diagnosing inflammatory bowel diseases.

The engineered strain of the gut bacteria E. coli senses pH and glows when it encounters acidosis, an acidic condition that often occurs during flare ups of inflammatory bowel diseases like colitis, ileitis and Crohn’s disease.

Researchers at the University of Colorado (CU) School of Medicine used the Rice-created organism in a mouse model of Crohn’s disease to show acidosis activates a signature set of genes. The corresponding genetic signature in humans has previously been observed during active inflammation in Crohn’s disease patients. The results are available online in the Proceedings of the National Academy of Sciences.

Study co-author Jeffrey Tabor, an associate professor of bioengineering in Rice’s Brown School of Engineering, whose lab engineered the pH-sensing bacterium, said it could be reprogrammed to make colors that show up in the toilet instead of the fluorescent tags used in the CU School of Medicine experiments.

“We think it could be added to food and programmed to turn toilet water blue to warn patients when a flare up is just beginning,” said Tabor.

Bacteria have evolved countless specific and sensitive genetic circuits to sense their surroundings. Tabor and colleagues developed a biohacking toolkit that allows them to mix and match the inputs and outputs of these bacterial sensors. The pH-sensing circuit was discovered by Rice Ph.D. student Kathryn Brink in a 2019 demonstration of the plug-and-play toolkit.

PNAS study co-authors Sean Colgan, the director of the CU School of Medicine’s Mucosal Inflammation Program, and Ian Cartwright, a postdoctoral fellow in Colgan’s lab, read about the pH sensor and contacted Tabor to see if it could be adapted for use in a mouse model of Crohn’s disease.

“It turns out that measuring pH within the intestine through noninvasive ways is quite difficult,” said Colgan, the Levine-Kern Professor of Medicine and Immunology in the CU School of Medicine.

So Brink spent a few weeks splicing the necessary sensor circuits into an organism and sent it to Colgan’s lab.  

“Normally, the pH in your intestines is around seven, which is neutral, but you get a lot of inflammation in Crohn’s disease, and pH goes to something like three, which is very acidic,” Tabor said.

Colgan and colleagues have studied the genes that are turned on and off under such conditions and “needed a tool to measure pH in the intestine to show that the things they were observing in in vitro experiments were also really happening in a live animal,” Tabor said.

“Colonizing this bacterial strain was the perfect biological tool to monitor acidosis during active inflammation,” Colgan said. “Correlating intestinal gene expression with the bacterial pH sensing bacteria proved to be a useful and valuable set of biomarkers for active inflammation in the intestine.” 

Tabor said he believes the pH-sensing bacterium could potentially be advanced for human clinical trials in several years. 

Tabor’s work was supported by the Welch Foundation and the National Science Foundation.

Gym Illustration by Rita Azar for 360 Magazine

UVA on Battling Diseases by Exercise

A top exercise researcher and colleagues at the University of Virginia School of Medicine have launched an ambitious effort to understand the whole-body benefits of exercise so that doctors can use that information to prevent and treat disease.

Zhen Yan, PhD, and his collaborators aim to identify the sources, functions and targets of the molecules that provide exercise’s well-documented health benefits. By understanding this, doctors will better understand how exercise helps fend off disease, and they may be able to design drugs to mimic those benefits for people who cannot exercise, such as those with limited mobility. The cutting-edge research could open new doors both for preventing and treating many common illnesses, the researchers hope.

“No one would dispute that physical activity or regular exercise is the best measures for health promotion and disease prevention,” said Yan, director of the Center for Skeletal Muscle Research at UVA’s Robert M. Berne Cardiovascular Research Center. “In fact, the health benefits of exercise are way beyond our imagination. The underlying reasons for the superb health benefits of exercise are being uncovered by many talented and passionate scientists around the world.”

Understanding How Exercise Improves Health

The UVA researchers have recently joined a national consortium seeking to create a “molecular map” of exercise benefits. Known as the Molecular Transducers of Physical Activity Consortium, or MoTrPAC, the group includes researchers at top institutions across the country, including Harvard, Duke, Stanford and Mayo Clinic.

The consortium came about after the National Institutes of Health invited Yan and a dozen other prominent scientists to a roundtable discussion in 2010 about the future of exercise research and the obstacles that stood in its way. The NIH then set aside almost $170 million for MoTrPAC’s research – believed to be the agency’s largest-ever investment into the mechanisms of how physical activity improves health and prevents disease.

“The program’s goal,” Yan explained, “is to study the molecular changes that occur during and after exercise and ultimately to advance the understanding of how physical activity improves and preserves health.”

The consortium is looking at exercise benefits in both humans and animal models. Initial animal research was conducted at Harvard, the University of Iowa and the University of Florida. In the latest round, UVA is joined by the University of Missouri, the University of Kansas Medical Center and the University of California, Los Angeles.

The vast amount of information collected as part of the project so far has poised the UVA team to make “unprecedented” advances, Yan reports. He and his multi-disciplinary team will employ advanced computer algorithms to sift through the heaps of data to identify specific molecules to study. They will then conduct state-of-the-art research in lab mice using gene editing, combined with a wide range of functional assessment, including muscle, cardiac, metabolic and cognitive/mental functions. This will let them determine the effects the molecules have and lay a foundation for doctors to harness the molecules to benefit human health in the future.

Yan’s team will work closely with colleagues at Stanford, who will conduct advanced “multiomics” analyses, meaning they will bring together data on genes, cellular proteins and much more to obtain a more holistic understanding of exercise’s benefits to the body.

UVA’s research team includes Yan, of the Robert M. Berne Cardiovascular Research Center and the Departments of Medicine, Pharmacology and Molecular Physiology and Biological Physics; Wenhao Xu, PhD, of the Department of Microbiology, Immunology and Cancer Biology; Chongzhi Zang, PhD, of UVA’s Center for Public Health Genomics, the Department of Public Health Sciences and the Department of Biochemistry and Molecular Genetics; Matthew Wolf, MD, PhD, of the Department of Medicine’s Division of Cardiovascular Medicine and the Robert M. Berne Cardiovascular Research Center; Thurl Harris, PhD, of the Department of Pharmacology; and Alban Gaultier, PhD, and John Lukens, PhD, both part of UVA’s Department of Neuroscience and the Center for Brain Immunology and Glia (BIG).

“It is well known that exercise is one of the best treatments for mood disorders,” Gaultier said. “We are excited to test the group discoveries using animal models of anxiety and depression.”

“This is an exciting opportunity for team science,” Zang said. “I am happy to work with colleagues at UVA and across the country and use data-science approaches to unravel the complex molecular effects of exercise.”

UVA’s effort has received almost a half-million dollars in backing from the NIH’s fund for MoTrPAC’s research.

“Our research team encompasses exceptional talents. The collective wisdom and expertise of the team at UVA and MoTrPAC will allow us to reach a level that we would not be able to reach by an individual,” Yan said. “It is an unprecedented opportunity in our lifetime to tackle this incredibly important question to mankind.”

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

MORE: Exercise may help prevent deadly COVID-19 complication.

Mina Tocalini, 360 Magazine, COVID-19

New Possible Key for Targeting Viruses

“Position 4” didn’t seem important until researchers took a long look at a particular peptide. That part of the peptide drawn from a SARS-CoV virus turned out to have an unexpected but significant influence on how it stably binds with a receptor central to the immune system’s ability to attack diseased cells. 

In a study published by the Proceedings of the National Academy of Sciences, researchers at Rice University’s Brown School of Engineering and the University of Texas MD Anderson Cancer Center revealed models at an atomic resolution that detail not only the binding but also, for the first time, the unbinding mechanisms that underlie a key component of the immune system. 

They say a better understanding of the entire mechanism could lead to advancements in immunotherapy that boost the body’s ability to fight disease. 

Rice computer scientist Lydia Kavraki, alumnus Jayvee Abella and postdoctoral researcher Dinler Antunes, led the study.

“Finding good targets to trigger a protective immune response is very challenging, especially in cancer research,” Antunes said. “The fact that this particular peptide was predicted not to bind to HLAs (human leukocyte antigens) by sequence-based methods highlights a blind spot in our current prediction capacity.”

“By incorporating structural analysis, we can detect the contribution of these secondary interactions to peptide binding and stability, hopefully enabling us to find better targets for antiviral vaccine development and T-cell-based cancer immunotherapy,” he said.

The researchers used their simulations to illuminate details of how the intracellular SARS peptide, QFKDNVILL, binds to an MHC receptor protein known as HLA-A24:02, primarily at dominant anchors on both ends of the peptide (at positions 2 and 9) and presents them for inspection to the immune system’s T cells. 

Stable binding of a peptide and MHC is a prerequisite to the activation of T cells, which look for peptides not normally found in healthy cells. If the peptide and protein don’t bind, the T cell is not prompted to attack. 

“That much was known from previous studies of the bound and unbound states of many such complexes,” Kavraki said. “What they didn’t capture was the intermediate states and the transitions that lead from one state to another, especially the unbinding.

“I think this is the only analysis that shows the unbinding of peptides from the MHC with atomic resolution,” Kavraki said. “Other peptides have similar characteristics and we think they would have similar behaviors.”

All of these interactions were revealed in great detail through Markov state models that analyze how systems change over time. In this case, the models revealed the importance of secondary sites that support the peptide’s primary anchors. That’s where position 4 stood out.

“There are the main, canonical anchors that people know, but there are these secondary interactions that contribute to the binding and the stability,” Antunes said. “These are harder to capture, but in this study, it seems that position 4 plays a very important role. When you mutate it, it affects the behavior of the peptide as it unbinds from the molecule.”

The researchers modeled mutations of the MHC to see how they would influence binding and found they supported the importance of position 4 to the stability of the complex.

“Our computational approach was able to make predictions on the effect of mutations that are then experimentally verified,” said co-author Cecilia Clementi, a former Rice professor who recently became Einstein Professor of Physics at the Free University of Berlin. 

The researchers developed a two-stage process to simplify the computational complexity of atom-scale analysis of large molecules. The first stage used a technique called umbrella sampling to accelerate the initial exploration of the molecules. The second, exploratory stage used adaptive sampling, in which simulations are driven to accelerate the construction of the Markov model.  

“The challenge is that these MHCs are pretty large systems for computational chemists to simulate,” said Abella, whose research on the topic formed much of his doctoral thesis. “We had to make some approximations and leverage advances in these classes of methods to move forward.”

“We’re not the first one to study unbinding, but what characterizes our work over others is that we keep full atomic resolution in our simulations,” he said. “Other works use a technique known as a Markov chain Monte Carlo, whereas we use molecular dynamics, which lets us incorporate time into our computation to capture the kinetics.”

Their methods can be applied to other peptide-MHC complexes with existing 3D models. “This was, in some sense, a feasibility study to show we can use molecular dynamics and build a Markov state model of a system this size,” Abella said. 

The researchers also noted the study’s relevance to the current fight against COVID-19, as the SARS peptide they viewed, QFKDNVILL, is highly similar to the NFKDQVILL peptide in SARS-CoV-2, with the same binding pockets in positions 2, 4 and 9.

“These results suggest that both peptides can bind to HLA-A*2402 and provide targets for anti-viral T-cell responses, which are of great interest in light of the current pandemic,” said co-author Gregory Lizée, a professor in the Department of Melanoma Medical Oncology at MD Anderson. “But these results also shed light on many other potential immune targets, including those of other viruses and even human cancers.”

Kavraki noted that experimental work by long-term collaborator Lizée and Kyle Jackson, a graduate research assistant at Lizée’s lab who produced the mutant proteins, were critical to validate their simulations. Kavraki’s own lab won a National Science Foundation (NSF) Rapid Response Research grant to help identify fragments of SARS-CoV-2 viral proteins as possible targets for vaccine development. 

Kavraki is the Noah Harding Professor of Computer Science and a professor of bioengineering, mechanical engineering and electrical and computer engineering. 

The Cancer Prevention and Research Institute of Texas, the Gulf Coast Consortia, the NSF, the Einstein Foundation Berlin and the Welch Foundation supported the research.