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New grasp of key COVID-19 protein may lead to a live-attenuated vaccine effective against more variants for longer
LAWRENCE — Research from the University of Kansas just published in Proceedings of the National Academy of Sciences could hasten development of a new class of vaccines aimed at SARS-CoV-2, the virus that causes COVID-19. Anthony Fehr, associate professor of molecular biosciences, led research into a protein dubbed “Mac1,” which has intrigued molecular bioscientists as an antiviral target because it’s known to help confer virulence, or the power to cause disease.
School of Engineering establishes virtual institute to combat cyber threats
LAWRENCE — A new virtual institute established at the University of Kansas School of Engineering will train the next generation of military and civilian leaders to better combat the growing threat of cyberattacks and protect the electromagnetic spectrum (EMS). The complexity and diversity of modern communication systems — such as 5G and 6G networks — as well as artificial intelligence and electronic warfare systems present daunting challenges in protecting networks from cyberattacks, said Fengjun Li, KU professor of electrical engineering & computer science.
Authors try to simplify difficult aspect of Russian language
LAWRENCE — Together with two native Russians, Stephen Dickey, professor from the Department of Slavic, German & Eurasian Studies, has written a new book that explores and allows mid- to advanced-level Russian language learners to practice verbal aspect, which has no equivalent in English. “It’s a book about a very stubborn part of Russian grammar,” Dickey said. The book is part of KU’s Libraries’ free, online Open Textbooks initiative, and the authors have been promoting its availability at a series of national and international teachers’ conferences.
Full stories below.
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Contact: Brendan M. Lynch, 785-864-8855, [email protected]
New grasp of key COVID-19 protein may lead to a live-attenuated vaccine effective against more variants for longer
LAWRENCE — Research from the University of Kansas just published in Proceedings of the National Academy of Sciences could hasten development of a new class of vaccines aimed at SARS-CoV-2, the virus that causes COVID-19.
Anthony Fehr, associate professor of molecular biosciences, led research into a protein dubbed “Mac1,” which has intrigued molecular bioscientists as an antiviral target because it’s known to help confer virulence, or the power to cause disease. Results have spurred several groups, including the Fehr lab, to begin developing novel inhibitors of Mac1.
“We’ve built up a body of literature showing this gene is critical for the virus to cause disease,” Fehr said. “To better understand this protein, we use what’s called reverse genetics, where we can delete or mutate this gene so it no longer functions in the context of the actual virus. While we’ve done this in a lot of different coronaviruses, we hadn’t actually explored this in SARS-CoV-2 until just recently. This paper really describes our efforts to get rid of this protein Mac1 in SARS-CoV-2 and really see what’s happening.”
Studying how SARS-CoV-2 behaved in mouse models, Fehr’s collaborator at Oklahoma State, Rudra Channappanavar and his group, found that without Mac1, the virus barely had an impact on the health of mice.
“If you look at the mouse data, we find that every mouse survived and showed no real signs of disease when they were infected with the virus without this gene, whereas when we give mice the normal virus — we would call it the ‘wild-type’ virus — every mouse dies,” Fehr said. “So, there’s a huge discrepancy in the ability of those viruses to cause disease. These results further demonstrate that Mac1 is a strong target for the development of novel antiviral therapies.”
What’s more, Fehr and his co-authors found the virus, without the Mac1 protein, induced a robust initial immune response in mice, the kind of biological response researchers look for in a vaccine target.
“That first response you have to a virus, called an innate immune response, is dramatically increased in this infection,” said the KU researcher. “When we infect the mice, this further improves the adaptive immune response, which is that T- and B-cell response we get that produces antibodies and antiviral T-cells later on — that can really protect us from future disease.”
Fehr and Channappanavar have already shown that prior infection with the attenuated virus can be protective for mice from a future infection.
“Right now, we’re really looking at further developing this virus into a live attenuated vaccine for SARS-CoV-2, and we’re working on different strategies with minor modifications to this virus to make it even better,” he said. “We think this is a great start to developing a vaccine that we think would have longer lasting immunity.”
Fehr said such a vaccine could be administered intranasally, targeting the lung, giving it advantages over today’s recommended vaccine regimen based on mRNA technology.
“One of the major problems with the current vaccines is that we give them in your arm — when you give a vaccine in your arm or your muscle, you don’t really get great immune responses in your lungs,” he said. “We think that live-attenuated vaccines given intranasally can improve that response.”
Additionally, live-attenuated COVID-19 vaccines could last longer than current vaccines requiring boosters.
“I don’t want to dis mRNA vaccines — they’re great,” Fehr said. “But they’re not particularly long-lasting. We’re finding their immunity wanes over the course of time. Live-attenuated viruses have been around for decades, and many of them are very effective and last very long. We can get a lot of live-attenuated vaccines as children, and we never have to take them again because they last our lifetime.”
According to Fehr, a live-attenuated vaccine would target parts of the virus more likely to remain the same from variant to variant.”
“All the current vaccines out there are really focused on a small portion of that spike glycoprotein that’s on the outside surface of the virus,” Fehr said. “There are a lot of parts of that that don’t change, and they’re sensitive to the current vaccines. But if there are changes in the spike protein, will those vaccines keep working? Mostly, they do. But some of them do lose efficacy.”
Fehr said a whole-virus vaccine, like the one his lab is investigating, could target regions of the genome that don’t change from variant to variant.
“It could reduce what I call ‘variant chasing’ that we have with a lot of our different vaccines now,” he said. “Hopefully this approach targeting the Mac1 could be beneficial in preventing disease from future variants.”
Fehr’s KU collaborators were lead author Yousef M. Alhammad, a former postdoctoral researcher, along with postdoctoral researcher Srivatsan Parthasarathy, doctoral students Joseph O’Connor, Catherine Kerr and Jessica Pfannenstiel; and Robert Unckless, associate professor of molecular biosciences, Edward & Thelma Wohlgemuth Faculty Scholar and director of the KU Center for Genomics. They were joined by co-authors Roshan Ghimire, Debarati Chanda, Caden Miller, Sunil More and Rudragouda Channappanavar from Oklahoma State University and Sonia Zuniga and Luis Enjuanes of the National Centre for Biotechnology, Campus Universidad Autónoma de Madrid in Spain.
“I’m really proud of this group. We all came together, worked really hard and produced some really great science,” Fehr said.
The work was funded at in part by grants from the NIH and with significant support from the Chemical Biology and Infectious Disease COBRE at KU, led by Scott Hefty, professor and chair of molecular biosciences at KU, and startup funds from KU and Oklahoma State University.
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Contact: Cody Howard, 785-864-2936, [email protected]
School of Engineering establishes virtual institute to combat cyber threats
LAWRENCE — A new virtual institute established at the University of Kansas School of Engineering will train the next generation of military and civilian leaders to better combat the growing threat of cyberattacks and protect the electromagnetic spectrum (EMS).
KU received a two-year, $1.5 million grant from the Department of Defense to establish the program, known as the Virtual Institutes for Cyber and Electromagnetic Spectrum Research and Employ, or VICEROY, Virtual Institute. The grant is overseen by the Griffiss Institute, which is a nonprofit talent and technology accelerator for the Department of Defense and an international network of academic, government and industry partners.
Fengjun Li, KU professor of electrical engineering & computer science and lead researcher for the VICEROY Virtual Institute, said the complexity and diversity of modern communication systems — such as 5G and 6G networks — as well as artificial intelligence and electronic warfare systems present daunting challenges in protecting networks from cyberattacks.
“We must manage and allocate scarce spectrum resources, detect and counter sophisticated signal jamming and interference, and maintain reliable and secure communication in contested environments,” Li said. “Successfully tackling these challenges requires education, training, research and teamwork across many disciplines.”
KU will partner with researchers at Ohio State University and Purdue University Northwest to develop new cybersecurity courses and curriculum to support more than 30 students each year across three universities.
The VICEROY Virtual Institute will officially launch in fall 2023. It will offer an augmented curriculum that enhances existing education in cyber and EMS operations through hands-on training, research-oriented experiential learning and several scholarships. The VI will provide four augmentation programs, including:
1. Cybersecurity theories and practices
2. Cyber and EMS operations
3. Data science in cyber and EMS applications
4. Strategic foreign language proficiency in Chinese
5. In addition, it will offer two special education and training programs for developing cyber talent and qualified cyber instructors in the form of summer camps, workshops and seminars.
“Equipping the future generation of military and civilian leaders with essential skills in cyber and EMS security through experiential learning is becoming more crucial in our interconnected society,” Li said. “Developing a pipeline of future cyber leaders is critical to these efforts and a key goal of this program.”
The KU School of Engineering has a long history as a national leader in cybersecurity and electromagnetic spectrum research. The federally funded Institute for Information Sciences (I2S) has researchers developing technology in the areas of cybersecurity, computing, communications, bioinformatics, signal processing and sensors. I2S is also home to cybersecurity research at KU and is continuously supported by the university.
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Contact: Rick Hellman, 785-864-8852, [email protected]
Authors try to simplify difficult aspect of Russian language
LAWRENCE – Stephen Dickey has specialized in the thorny problem of aspect – which has challenged linguists and learners of Russian around the globe — when it comes to the proper usage of verbs in the Russian language.
“I have researched this category as a linguist for a few decades, but I’ve never written any instructional material for it until now,” said Dickey, professor in the University of Kansas Department of Slavic, German and Eurasian Studies.
Together with two native Russians – KU doctoral student Kamila Saifeeva and KU doctoral graduate Anna Karpusheva, Dickey has written a new book titled “Russian Aspect in Conversation.” Published earlier this year, it is part of KU’s Libraries’ free, online Open Textbooks initiative, and the authors have been promoting its availability at a series of national and international teachers’ conferences.
It’s not a course textbook, Dickey said, but rather a complementary work that explores and allows mid- to advanced-level Russian language learners to practice verbal aspect.
“It’s a book about a very stubborn part of Russian grammar,” Dickey said.
That’s because, Dickey said, there is no equivalent in English.
“The category that we’re talking about is more or less on a par with English ‘was reading’ versus ‘read,’ ” Dickey said. “So you’ve got one verb form that refers to a completed action, and then you’ve got another verb form that refers to an action that’s ongoing. And any time a Russian uses a verb, they have to make this choice. So we rarely say ‘be reading’ as a command to somebody. We will say ‘read this’ and ‘read that.’ But Russians will say the equivalent of ‘be reading’ all the time.”
These Russian verbal categories are known as “perfective” verbs for actions that are or have been completed, and “imperfective” verbs for actions that are or might be ongoing.
“The mind-bending part of this is that it is more about reference,” Dickey said. “The difference between these two forms in Russian is kind of like the meaning of saying ‘the book’ versus ‘a book’ or ‘books.’ It’s about specific things versus nonspecific things.
“And if you think that this doesn’t make any sense, you’re in good company, because we just don’t think about verbal actions as being specific versus nonspecific. They take that kind of referential opposition and they lay it onto the verbs. And then you have the ‘read’ form, which is specific, versus ‘is reading’ or ‘be reading,’ or what have you, which is the nonspecific one. And it is extraordinarily difficult for people to get.
“There are people who do speak Russian for decades and don’t perfect it, and that is really the impetus for this book.”
It’s a crucial thing for approaching fluency, Dickey said.
He and his colleagues created a book with some brief introductory material and a series of more than two dozen practice modules to help students get it.
“You read a series of dialogues, and then you answer multiple-choice questions about them … that are designed to get you thinking about what is the relationship between the speaker and the hearer in the dialogue, and what the speaker wants to accomplish,” Dickey said.
Choosing the correct answer gets the student a confirmation with a gold star appearing on the screen/page. If they choose the wrong answer, the text lets them know that, too, and they can try again to get it right. Each module concludes with some explanatory material, summing up the section.
Dickey said while working with a teacher’s guidance would obviously be helpful, the book is designed to be able to be used independently by students. Moreover, he said, students can dip in and out of the book, taking on one bite at a time.
“That’s the challenge,” he said. “To take to take what is ultimately a very difficult category and break it down so students can acquire it and use it.”
Dickey said that since the book was published earlier this year, he and his co-authors have been promoting its availability at a series of national and international teachers’ conferences.
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