Biochemistry

U of T’s Medicine by Design invests $1 million to advance new ideas in regenerative medicine – News@UofT

Patients with cystic fibrosis experience recurrent lung infections that eventually destroy their airways, shortening their average life expectancy to 50 years in Canada. Current drug treatments, which target a malfunctioning pathway in cells that causes the infections, are costly and have varying effectiveness.

Now, with funding from Medicine by Design, a researcher at the Hospital for Sick Children (SickKids) is combining stem cells, gene editing and computational modelling to try to hijack an alternative cell pathway in the hopes of restoring lung function in these patients.

If successful, our study will be the first to provide proof-of-concept that this alternative approach to treating cystic fibrosis is effective, saysAmy Wong, a scientist working in developmental and stem cell biology at SickKids who is also an assistant professor in the department of laboratory medicine and pathobiology in the University of Torontos Temerty Faculty of Medicine.

Wongs project is one of seven across U of T and its affiliated hospitals that have been awarded 2020New Ideas AwardsandSeed Fundawards from Medicine by Design. Through a $1 million investment, Medicine by Design is supporting research aimed at advancing new concepts expected to be important to regenerative medicine in the coming years. The funded projects will have potential impacts in diseases and conditions such as vision loss, amyotrophic lateral sclerosis (ALS), intestinal disease in premature babies and more.

Supporting novel strategies and approaches is crucial to moving regenerative medicine into the future, saysMichael Sefton, executive director of Medicine by Designand a University Professor at U of Ts Institute of Biomedical Engineeringand thedepartment of chemical engineering & applied chemistry in the Faculty of Applied Science & Engineering.

Our 2020 New Ideas project portfolio integrates mathematical modelling, physics and computational biology with stem cell biology and biomedical engineering, and strengthens engagement with clinicians who are key to translating our research into patient impact. We are particularly delighted this year to support so many outstanding early-career researchers, who will ensure Toronto remains a global leader in regenerative medicine for years to come.

Wong is one of three investigators to receive a 2020 New Ideas Award, which is valued at $100,000 per year for up to two years. Four additional projects were selected for Seed Fund Awards of $100,000 each for one year to further develop their potential.

Medicine by Design selected the funded projects from among 36 short-listed proposals, which were evaluated and ranked through an external peer review process. Applications were submitted by clinicians and researchers at U of T and its affiliated hospitals from a wide range of disciplines including biochemistry, biomedical engineering, developmental and stem cell biology, immunology, neuroscience and surgery.

Medicine by Design builds on decades of made-in-Canada excellence in regenerative medicine dating back to the discovery of stem cells in the early 1960s by Toronto researchers James Till and Ernest McCulloch. Regenerative medicine uses stem cells to replace diseased tissues and organs, creating therapies in which cells are the biological product. It can also mean triggering stem cells that are already present in the human body to repair damaged tissues or to modulate immune responses. Increasingly, regenerative medicine researchers are using a stem cell lens to identify critical interactions or defects that prepare the ground for disease, paving the way for new approaches to preventing disease before it starts. Medicine by Design is made possible thanks in part to a $114-million grant from theCanada First Research Excellence Fund.

Current cystic fibrosis drug treatments target a genetic mutation that causes epithelial cells, which line the airway and act as a barrier against viruses, to function improperly. The mutation affects the function of an important ion channel in cells, called CFTR, which helps to maintain the right balance of fluid in the airways. Poor function causes mucosal obstructions in the airways and prevents clearance of foreign pathogens, which leads to chronic infections and ultimately destroys airway tissue.

In her project, Wong will explore an alternative ion channel in the epithelial cells to determine if it can be hijacked and used to compensate for the lack of function caused by the mutant CFTR. The research will be conducted using a combination of stem cell-derived lung models, gene editing and computational modelling.

Wongs project builds on decades of cystic fibrosis research at SickKids, where the cystic fibrosis gene was first identified 30 years ago.

To date, more than 2,000 mutations in the cystic fibrosis gene have been identified, says Wong. SickKids scientists and U of T researchers have become the epicentre of incredible cystic fibrosis research to understand how this disease works at the genetic and molecular level.

Wong says that, while the idea of targeting an alternative pathway is not necessarily ground-breaking on its own, its the array of tools now available that makes the idea a potential game changer.

We have access to an incredible resource of primary cells and stem cells from more than 100 individuals with cystic fibrosis harbouring various mutations. Wong says.Our lab has developed human lung models from stem cells that can be used to model lung disease such as cystic fibrosis. And with new advanced tools in single-cell genomics and gene-editing, coupled with key collaborations for computational modelling, we are poised to find new therapeutic targets for cystic fibrosis.

Leo Chou, an assistant professor at the Institute of Biomedical Engineering, andHyun Kate Lee, an assistant professor in the department of biochemistry in the Temerty Faculty of Medicineboth Medicine by Design New Investigators are also leading 2020 New Ideas projects.

Chou, along with co-investigatorsJulie Lefebvre, a scientist at SickKids and U of T assistant professor of molecular genetics, andValerie Wallace, a senior scientist at the Krembil Research Institute, University Health Network and a U of T professor of laboratory medicine and pathobiology and ophthalmology, will focus on cell transplantation in the retina, a process that has demonstrated encouraging pre-clinical results such as partial vision restoration in several animal disease models.

Recent research had demonstrated that this restoration is a result of the transfer of proteins complex molecules required for the structure, function and regulation of the bodys tissues between host tissue and donor cells. But the scope of that transfer process is not well understood. Chous project will develop an imaging approach to detect the transfer of mRNA molecules between host and donor cells. The outcomes from this project will inform the future design of cell transplantation therapies and lead to novel methods to deliver therapeutics. This project could improve therapies for retinal diseases and visual impairments, and inform strategies for other degenerative disorders.

Lee and co-investigatorPenney Gilbert,an associate professor at the Institute of Biomedical Engineering, will look at a common but not well-understood structure called the neuromuscular junction (NMJ), which mediates communication between neurons and muscles throughout the body. Defects in NMJ integrity and function underlie fatal diseases such as ALS. NMJ diseases, which affect more than 500,000 people globally, lack effective treatments. This project will use stem cells derived from reprogrammed skin cells of healthy people to develop NMJs in culture. Through high-resolution imaging, the healthy human NMJs will be studied both on their own and along with NMJs built from ALS patient cells. Through this work, the research team aims to identify genes to target to improve the health of NMJs, which could eventually help prevent or delay NMJ degeneration and even promote regeneration.

Michael Garton, an assistant professor at the Institute of Biomedical Engineering, has received a Seed Fund award to tackle the challenge of translating the genetic tools of synthetic biology an area of research that aims to create or redesign biological components using engineering methods into effective medical therapies against a number of diseases.

But they are difficult to translate into human therapies, Garton says, because the bodys T-cells immune cells that detect and destroy cells containing foreign material will identify these tools as foreign and destroy them.

Instead of switching off the T-cells, Gartons goal is to use computational modelling and high-throughput screening to selectively turn off the bodys foreign antigen display system so the immune system will still respond to foreign invaders when necessary, but allow cells containing synthetic tools to survive. If successful, this approach could enable a new generation of synthetic biology-enhanced cell therapies for a range of diseases.

Medicine by Design funding will help to facilitate the integration of synthetic biology and regenerative medicine and aid the development of cell-based therapies that perform better than nature, says Garton.

Other Seed Fund projects will encompass research in repairing the heart after paediatric cardiac surgery, treating an intestinal emergency in premature babies and creating a database for cell lineage paths.

John Parkinson, a senior scientist at SickKids and a U of T professor of biochemistry and molecular genetics, along with co-investigatorsJason Maynes, Wasser Chair in Anesthesia and Pain Medicine at SickKids and a U of Tassociate professor of anesthesiology and biochemistry, andWilliam Navarre, an associate professor in the department of molecular genetics, will investigate manipulating the microbiome, or community of microorganisms in the gut, to improve cardiac repair in post-operative treatment of a congenital heart disorder. Through a process that will identify prebiotics in breast milk that help enhance the production of molecules that research has shown can aid cardiac repair, the team will organize both observational (how disease alters the microbiome) and interventional (how the microbiome alters the disease) multi-site trials, which will provide the opportunity to immediately translate findings into changes in patient care regimens and improve outcomes.

CliniciansAgostino Pierro, a surgeon at the Division of General and Thoracic Surgery at SickKids and a U of T professor of surgery and physiology, and Philip Sherman, a senior scientist and gastroenterologist at the Division of Gastroenterology, Hepatology and Nutrition at SickKids and U of T professor of dentistry, pediatrics and laboratory medicine and pathobiology, have proposed a novel way of enhancing gut repair for a common intestinal emergency in premature babies, called necrotizing enterocolitis (NEC). A leading cause of death for these infants, NEC causes complications such as blindness, intellectual disability, repeat hospitalizations and gut damage even in those that survive. This project will look at whether intestinal organoids organ-like structures grown in the laboratory from stem cells that mimic some of the functions of native intestines can potentially stimulate repair of the gut and recovery from NEC. The project will define how to best transplant organoids, identify how the organoids protect the intestine from injury and assess if organoid transplantation is a valid new treatment for NEC.

Lincoln Stein, who is head of adaptive oncology at the Ontario Institute for Cancer Research and a professor in the department of molecular genetics at U of T, has received seed funding to build a database called Cytomics Reactome, which will be freely available to Canadian and international researchers. The database will build on recent technologies that open the door to the possibility of deciphering cell lineage paths the series of steps that lead a young, undifferentiated cell into a specialized one at single-cell resolution. To accelerate the path from basic research to clinical application, the database will systematically organize pre-existing knowledge of cell lineage paths into a comprehensive, interactive and easily accessible map that can serve as a framework for interpretation and integration of the latest experimental findings.

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U of T's Medicine by Design invests $1 million to advance new ideas in regenerative medicine - News@UofT

Biochemistry

Faculty and Staff Receive Nearly $9 Million in Grants, Contracts in Q1 – CSUF News

Cal State Fullerton faculty and staff received close to $9 million in funding during the first quarter of the university's 2020-21 fiscal year. Supported projects ranged from developing a robotic aid system for blinded veterans and documenting the experiences of underrepresented women in California agriculture, to funding CSUF's GEAR UP and Upward Bound programs.

Dawn Macy, director of the Center for Internships and Community Engagement: $1,780,840 in total funding

Joshua Bilbrew,director of CSUFs GEAR UP program: $1,116,440 from the U.S. Department of Education in support of Gaining Early Awareness and Readiness for Undergraduate Programs (GEAR UP).

Diana Vasquez, director of CSUF Upward Bound: $728,821 in total from the U.S. Department of Education

David Chenot, professor of social work: $658,279 continuing award from the Health Resources and Service Administration for the Health Careers Opportunity Program.Related: Program Helps Students See the Opportunities inAllied Health Care

Sadeeka Al-Majid, professor of nursing: $650,000 in first-year funding for a $3.25 million grant from the Health Resources and Services Administration for the project "Scholarships for Disadvantaged Students/Enriching Nursing Representation to Impact Community Health."Related: $3.25 Million Grant to Increase Pipeline of Nurses in Underserved Communities

Alyssa Hernandez, director of Educational Talent Search: continuation awards totaling $605,788 from the U.S. Department of Education

Brady Heiner, associate professor of philosophy: $540,218 in total. He received $50,000 from the North Orange County Public Safety Task Force for the "Project Rebound House Initiative, CSUF Year 4" project, and $490,218 from the State of California

Related: Boundless Opportunity: Project Rebound Opens Doors for the Formerly Incarcerated

Stephanie Vaughn, professor of nursing emeritus: $494,061 continuing grant from the Health Resources and Services Administration for the project titled "EMBRACE: Enrichment Markers of Better Relationship, Academics and Cultural Enhancement."Related: EMBRACE Promotes Cultural Sensitivity, Workforce Diversity in Nursing

Nicholas Brubaker, assistant professor of mathematics, and Wylie Ahmed, assistant professor of physics: $364,582 from the National Science Foundation for the project titled "RUI: Active Noise in the Dynamics of Self-Propelled Particles Stochastic Modeling and Experiments."

Gina Passante, associate professor of physics: $347,901 from the National Science Foundation for the project titled "Collaborative Research: Connecting Spins-First Quantum Mechanics Instruction to Quantum Information Science."

Kelvin Billingsley, associate professor of chemistry and biochemistry: $319,500 in continuing funding from the National Institutes of Health for the project titled "Hyperpolarized 13C Probes for Imaging Warburg Metabolism in Cancer."

Joshua Smith, professor of physics: $254,559 in total from the National Science Foundation

Kiran George, professor of computer engineering: $199,211 from the U.S. Department of Veterans Affairs for "Design and Development of a Teach-by-Showing Paradigm-Based Robotic Aid System for Blinded Veterans."

Sara Johnson, professor of anthropology: $150,000 from the U.S. Department of Agriculture for the "U-ACRE Project: Broadening Opportunities for High Impact Service-Learning Experiences in Agroecological Research" project.Related: Lessons From the Lowly Sweet Potato: U-ACRE Researchers Unearth Knowledge and Cultivate Sustainability

Adam Roberts, assistant professor of psychology: $110,985 from the National Institute of Health for the "Mapping Neural Connectivity in Zebrafish Larvae Using a Photoconvertible Protein" project.

Yinfei Kong, associate professor of information systems and decision sciences: $98,632 continuing award as part of a four-year National Institutes of Health grant for the project "Gender Disparities in Access and Engagement In Medication-Assisted Treatment for Opioid Use Disorder" in collaboration with the University of Chicago.Related: Titan Data Scientist to Study Gender Differences inOpioid Treatment

Geoffrey Lovelace, associate professor of physics: $84,668 continuing award from the National Science Foundation for the CAREER project titled "Computational Gravitational-Wave Science and Education."

Zair Ibragimov, professor of mathematics: two awards from University Enterprises, Inc., totaling $82,500 for "CSU-LSAMP 2018-2023." The Louis Stokes Alliance for Minority Participation is a program to increase disadvantaged students' preparedness, persistence and retention in STEM programs.

Adriana Badillo, program director of the Center for Educational Partnerships: $76,621 continuation award from the City of Anaheim for the College Internship Program.

Jocelyn Read, assistant professor of physics: $67,213 from the National Science Foundation for "RUI: Dense Matter and Gravitational Waves: The Coalescence of Neutron Star Binaries."

Michael Boytim, assistant director of the nurse anesthesia program: $44,630 from the Health Resources and Services Administration for the Nurse Anesthetist Traineeships project.Related: Titans Test Use of Anesthesia Machinesas Ventilators for COVID-19 Patients

Danielle Zacherl, professor of biological sciences: $33,304 from Orange County Coastkeepers for the project titled "Newport Bay Living Shorelines Project."

Marcelo Tolmasky, professor of biological science: $24,659 from the San Diego State University Research Foundation for the San Diego-MHRT project.

Natalie Fousekis, professor of history: $24,580 from the U.S. Department of Interior, National Park Service for "Documenting the Experiences of Mexican, Filipina and Chicana Women in California Agriculture."

Jessica Jaynes, assistant professor of mathematics and Valerie Poynor, assistant professor of mathematics: $19,812 from Los Angeles City College for the "STEM Pathways Program Summer Research 2020" project.

Robert Lockie, associate professor of kinesiology: $19,071 from the National Strength and Conditioning Association Foundation for the project titled "The Effects of Structured Strength and Conditioning Programs on Motor Skills, Movement Competency and Physical Fitness of High School Athletes."

Jennifer Burnaford, professor of biological science: $16,238 continuing award from UC Santa Cruz for "Assessment of Rocky Intertidal habitats for the California Marine Protected Area Monitoring Program."

Michael Groves, assistant professor of chemistry and biochemistry: $16,005 in first-year funding of a three-year award from the American Chemical Society for the project titled "Calculating Reaction Barriers for Benzene Hydroxylation to Phenol Using Graphene Based Catalysts."

Dorothy Woolum, professor emeritus of physics: $10,000 from the California Institute of Technology for the project titled "Genesis Samples."

Do Kyeong Lee, assistant professor of kinesiology: $8,820 continuation award from New York University for the "Play and Learning Across a Year" project.

Bo Y. Park, assistant professor of public health: $8,000 from the University of Southern California for "Planning and Engaging in Advance Care for Health (PEACH)."

Contact: Karen Lindell, klindell@fullerton.edu

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Faculty and Staff Receive Nearly $9 Million in Grants, Contracts in Q1 - CSUF News

Biochemistry

UCI researcher receives NIH Transformative Research Award – UCI News

Irvine, Calif., Oct. 6, 2020 University of California, Irvine biomedical engineer Chang Liu is the recipient of one of nine Directors Transformative Research Awards this year from the National Institutes of Health under its High-Risk, High-Reward Research Program, the agency announced today.

Lius five-year, $8.4 million grant will support a project to develop a system for making antibody generation a routine and widely accessible process.

It is hard to overstate the importance of monoclonal antibodies in the life sciences, said Liu, UCI associate professor of biomedical engineering who also holds appointments in the Department of Chemistry and Department of Molecular Biology & Biochemistry. Antibodies are critical tools in biomedical research and diagnostics, and they are a growing class of therapeutics to combat cancer and pathogens up to and including the virus responsible for COVID-19.

Liu said current methods for making custom antibodies are slow, costly, inaccessible to most researchers and often unsuccessful. His NIH proposal centers on simplifying the process through continuous and rapid evolution of high-quality antibodies requiring only the simple culturing of yeast cells.

He said his autonomously evolving yeast-displayed antibodies technology could have a transformative impact across the biomedicine field by turning monoclonal antibody generation into a rapid, scalable and accessible process where any lab with standard molecular biology capabilities can generate custom antibodies on demand.

We believe this can be achieved by combining our new technology for continuous protein evolution, a yeast antigen-presenting cell that we will engineer, and cutting-edge generative machine learning algorithms for antibody library design, he said.

Liu said that in addition to the continuous directed-evolution techniques that he has invented in his UCI laboratory, the project will rely on antibody design and artificial intelligence expertise provided by his collaborators and co-PIs of the project, Andrew Kruse and Debora Marks at Harvard Medical School.

The project could potentially result in an explosion of crowdsourced antibody sequence data that will train our machine-learning algorithms to design better antibody libraries for our autonomous evolution system, starting a virtuous cycle, he said.

In addition to contributing to cancer and anti-viral therapies, Liu said he and his fellow researchers will attempt to generate nanobodies against biogenic receptors that respond to acetylcholine, adrenaline, dopamine and other neurotransmitters. The goal of this work will be to develop a better understanding of psychopharmaceuticals in neurobiology and addiction.

In the past, the Transformative Research Award has allowed some of the most ambitious and impactful ideas in biomedicine to blossom, and several previous winners are scientific heroes of mine, said Liu. We have big shoes to fill, but we are up to the challenge.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs. Its located in one of the worlds safest and most economically vibrant communities and is Orange Countys second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.

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UCI researcher receives NIH Transformative Research Award - UCI News

Biochemistry

Growth of Electrolyte and Biochemistry Analyzers in Global IndustryOverview, Size and Share 2020-2025 – PRnews Leader

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Growth of Electrolyte and Biochemistry Analyzers in Global IndustryOverview, Size and Share 2020-2025 - PRnews Leader

Embryology

Alumni Spotlight- Procopio brothers and the biology of college life – Knight Crier

Submitted Photo

Kyle and Dylan Propcopio, Class of 2020 NPHS grads

The electric buzz backstage before a performance is a feeling known very well to both Dylan and Kyle Procopio.

The dynamic duo reminisce on their time at North Penn with smiles. While at the high school, they were assistants to the Stage Manager in all NPHS theatre productions, cabinet participants in Thespian Troupe, and members of SGS (Stimulation Gaming Society) and National Honors Society. Additionally, they were tremendously involved in Boyscout Troop 51.

Currently studying at Millersville University, the Procopios are both majoring in biology. Kyle, with a concentration in molecular genetics, and Dylan with a double major in secondary education.

Did you have a favorite class you attended while at NP?

Kyle- Definitely Genetics and Embryology with Mr. Christopher! Both Dylan and I enjoyed the curriculum and his teaching style.

Do you plan on being involved in theatre in some aspect during college?

Dylan- Yes! I had a wonderful experience during my involvement with NPHS theatre. I plan on participating in stage crew here at Millersville in any capacity. But, everything is on hold until the pandemic settles down.

What was the transition like from NPHS to Millersville?

Kyle- I was a little nervous about going to Millersville since the coronavirus is still happening. But even with some serious precautions, the transition was pretty smooth. We both found a strong group of friends. And even though the school is a little bigger, it definitely feels like home.

What inspired you to go into biology education?

Dylan- I always loved biology! During boy scouts, I was in charge of instructing some of the newer guys in our troop. I taught them certain nature skills and survival tactics, and I really found it rewarding.

What words of wisdom would you like to give current students at North Penn?

Kyle- Make the most of your time at North Penn! Of course, remember time management is important, but dont forget to make time with friends and activities youre interested in. Those are the memories that will last you a lifetime.

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Alumni Spotlight- Procopio brothers and the biology of college life - Knight Crier

Immunology

What we know about COVID-19 and immunity – PolitiFact

Since his return from Walter Reed National Military Medical Center, President Donald Trump has repeated that he may now be "immune" to the coronavirus. In a video released shortly after he arrived back at the White House, he said, "Now Im better, and maybe Im immune, I dont know."

In a 55-minute interview on Fox Business, he made several claims about his health and COVID-19 immunity, saying, "When you catch it you get better, and then youre immune," and jokingly referred to himself as a "perfect physical specimen."

But medical experts say there are still a lot of unknowns about COVID-19 immunity.

Do all recovered COVID-19 patients become immune, regardless of the severity? For how long? Will the virus behave like the flu, requiring a vaccine each year? How do we achieve herd immunity?

We spoke with immunology and infectious disease experts about what they have learned and still dont know about COVID-19 and immunity.

Heres what we found out.

How does COVID-19 immunity work?

A person achieves immunity to a disease when the bodys immune system has fought off the virus once and is now strengthened to resist further attack. The immune system has a kind of memory for previous pathogens, allowing the body to have a quicker, stronger response the next time it encounters a past invader.

This can happen naturally or via vaccine.

Medical experts say its hard to know for certain the strength and length of immunity for recovering COVID-19 patients, because its a new virus and not enough studies have been done. However, there are indicators that suggest there is some natural protection against the disease post-recovery.

The biggest clue is that recovered patients rarely get reinfected with COVID-19, experts said, especially when considering the huge number of people who have been infected with the virus around the world.

"The very high-level picture is pretty stable," said Dr. Sarah Fortune, chair of the Immunology and Infectious Diseases department at Harvard T.H. Chan School of Public Health.

"Both the clinical data and the animal studies suggest that there is meaningful protection against disease," Fortune said. "Its not as if youre seeing rampant recurrent infections with recurrent severe symptoms. Its not as if there are no cases, but by and large you're seeing substantial protection against disease."

Experts also said previous studies that looked at common cold coronaviruses showed that people develop immunity for extended periods of time (at least a year), though it varied slightly from case to case.

There may be some differences in the level of immunity for those who had a serious infection, versus those who only experienced mild symptoms, researchers say. Generally, patients who dealt with a severe infection are likely going to have a higher antibody count.

"But that doesnt mean that your mild infection isn't providing you enough immunity to protect you against the disease," Fortune said. "Even if its lower, it appears to be completely proficient in protecting you against the disease. And, in most of the people who are infected, they develop a mild case and we arent seeing many reinfections."

How long does immunity to COVID-19 last?

Theres no standard time frame for immunity after someone recovers from COVID-19. Different public health groups have different estimates, with the most conservative being about four months

Researchers say its likely that people are immune for longer, but note that with a rapidly spreading disease that has no cure, people should keep their guard up rather than return to life as normal and put themselves and others at risk.

One common misconception immunologists raised is the public perception of immunity in general, with many people thinking youre either immune or youre not. Thats not how it works.

"Protection is not like a light switch, its like a dimmer switch," Fortune said. "You will be more protected in the beginning, and over time that protection might wane, but its not going to just go away.

For example, as a persons immunity wanes, they may eventually get infected from the virus again, but not actually get sick. Or even further out, they may get infected and then have mild symptoms but nothing severe.

The takeaway: The loss of immunity is gradual, not drastic.

Will we have to get multiple vaccines for COVID-19, like the flu?

The flu is a respiratory virus like the coronavirus, but its also quite different. The flu rapidly shifts and mutates, making it more resistant to long-term immunity. Thats why there is a new vaccine each year.

If the virus that causes COVID-19 continues to behave like other coronaviruses, people will likely have more stable immunity from a limited vaccination schedule.

"There's no evidence, so far, that people will need to be vaccinated each year because of the virus mutating," said Dr. Stanley Perlman, a professor of microbiology and immunology at the University of Iowa. "That may be because of their immunity waning, but not because the virus is changing."

Fortune agreed. "Theres no evidence that Sars-Cov-2 (the virus that causes COVID-19) is going to, or has undergone, a really dramatic re-shuffling that makes it escape either a natural immunity or even a vaccine-induced immunity," she said. "That's not to say that its not possible there wont be a new one in the future, but just that the virus doesn't share the same characteristics of the seasonal, whole-scale remaking of itself that the flu does."

Does a positive antibody test mean a person is immune?

Positive test results dont guarantee immunity. The presence of antibodies only means that the person has been exposed to the virus in the past.

How sensitive, or how "good," the antibody test is, and the amount of antibodies a person has, weighs heavily on whether or not they would be considered immune from the virus.

The same thing is true with a PCR diagnostic COVID-19 test.

"Some people have very positive PCR tests and thats more of a worry than someone with fluctuating PCR tests negative one day, positive the next because they have less of a viral load," Perlman said. "Its the same thing with antibodies. You can test positive for antibodies but have so little that it doesnt really protect you, or you can have a high number of antibodies, which means youre better protected. The amount matters."

What about herd immunity?

Herd immunity is the idea that when enough people in a population are immune, either by having the infection or receiving a vaccine, the virus will have trouble spreading. Thats because an infected person is less likely to encounter a non-immune person to pass it on to, making them a dead-end in the chain of transmission.

When that happens enough times on a large scale, it drives its rate down and eventually gets the disease under control, but it doesnt necessarily eradicate it.

RELATED: Corralling the facts on herd immunity

The U.S. is still considered far from adequate COVID-19 herd immunity, and experts say there would have to be many more cases and deaths before we get there if a vaccine doesnt arrive first. Fewer than 1 in 10 Americans show signs of past infection as of late July, according to a Sept. 25 study published in The Lancet journal.

So, experts agree that the ideal way to achieve herd immunity is with a vaccine. While some immunity within a population is better than none, with a virus that spreads through the air, the higher the number of people who are immune, the better.

Different numbers have been tossed around by scientists on just how much of the population needs to be immune in order for herd immunity to work well. The mathematical model for Sars-Cov-2 which is derived based on the virus transmission characteristics and on how the population behaves puts it around 60-70 people out of every 100.

For the most highly contagious diseases, like measles, scientists say about 94% of the population needs to be immunized to achieve that level of protection.

"That doesn't mean that it goes away when we reach herd immunity, it just means that you're not propagating the epidemic," Fortune said. "People should have that in mind with herd immunity, and with the future, it's not like one day, we achieved herd immunity and its gone."

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What we know about COVID-19 and immunity - PolitiFact

Immunology

Nature Publishes New Research from Vir Biotechnology Demonstrating the Capacity of Enhanced Monoclonal Antibodies to Induce Protective Adaptive…

SAN FRANCISCO, Oct. 09, 2020 (GLOBE NEWSWIRE) -- Vir Biotechnology Inc. (Nasdaq: VIR) today announced the publication of preclinical research in an influenza animal model highlighting a new mechanism for enhancing the efficacy of monoclonal antibodies to treat viral infection and induce a protective response. Data demonstrate that selective engagement of an activating Fc receptor on dendritic cells by antiviral monoclonal antibodies induced protective CD8+ T cell adaptive responses. The paper, entitled Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection, was published in the October 8, 2020 online edition of Nature.

In the past several years, we've gained a better understanding of how integral Fc mediated effector functions of monoclonal antibodies are for their therapeutic efficacy in pre-clinical models of neoplastic, infectious and inflammatory diseases, said Jeffrey V. Ravetch, M.D., Ph.D., study senior author and Theresa and Eugene M. Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University. These approaches have been successfully applied to anti-tumor therapeutics and have resulted in improved clinical outcomes in a variety of oncologic diseases. Our present studies have uncovered a significant new mechanism by which antibodies, through their Fc region, can not only engage innate immune responses but activate adaptive T cell responses, thereby stimulating protective anti-viral immunity in these models.

The research published in Nature focuses on the role of the Fc domain of monoclonal antibodies, regions with the capacity to bind to other immune cells through a family of receptors (the Fc receptors). By engineering antibodies with modified Fc domains to enhance binding to specific Fc receptors on innate immune cells, investigators observed an enhanced protective immune response. Certain modifications (GAALIE variants) were associated with activation of dendritic cells, as well as antiviral effector T-cells, indicating induction of the adaptive arm of the immune system, which is responsible for long-term immunity. Based on this research, monoclonal antibodies programmed with improved effector function represent a potential new approach in the design of therapeutic antibodies for both the prevention and treatment of infectious diseases.

By observing and learning from our bodys powerful natural defenses, we have discovered how to maximize the capacity of antibodies through the amplification of key characteristics that may enable more effective treatments for viral diseases, said Herbert Skip Virgin, M.D., Ph.D., study co-author and executive vice president, research, and chief scientific officer of Vir. These data may have significant implications across a wide range of infectious diseases, and we look forward to exploring the vaccinal potential of the GAALIE-engineered antibodies we are advancing through clinical development VIR-3434 for chronic hepatitis B and VIR-7832 for SARS-CoV-2.

The preclinical study was conducted by Dr. Ravetch and Stylianos Bournazos, Ph.D., of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University, in collaboration with Dr. Virgin and Davide Corti, Ph.D., senior vice president of antibody research at Virs subsidiary Humabs BioMed SA.

This type of exceptional collaborative partnership between cutting-edge science and clinical application has the potential to significantly improve our ability to address infectious diseases, stated Dr. Virgin.

Vir is currently evaluating several monoclonal antibodies that have been Fc engineered to include the XX2 vaccinal mutation (or GAALIE variant) for which Vir has licensed exclusive rights for all infectious diseases.

About VIR-3434VIR-3434 is a subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. VIR-3434 has been engineered to have an extended half-life as well as to potentially function as a T cell vaccine against HBV in infected patients.

About VIR-7832VIR-7832 is a monoclonal antibody that has shown the ability to neutralize SARS-CoV-2 live virus in vitro. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (also known as SARS), indicating that the epitope is highly conserved, which may make it more difficult for escape mutants to develop. VIR-7832 has been engineered with the potential to enhance lung bioavailability, have an extended half-life, and function as a therapeutic and/or prophylactic T cell vaccine. VIR-7832 is being developed by Vir and its partner GlaxoSmithKline plc(LSE/NYSE: GSK) as part of their broader collaboration to research and develop solutions for coronaviruses, including SARS-CoV-2.

About Vir BiotechnologyVir Biotechnology is a clinical-stage immunology company focused on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. Vir has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Its current development pipeline consists of product candidates targeting hepatitis B virus, influenza A, SARS-CoV-2, human immunodeficiency virus and tuberculosis. For more information, please visitwww.vir.bio.

Vir Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as potential, may, will, could, expect, plan, anticipate, believe, estimate, goal, intend, candidate, continuing, developing and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Virs expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the ability of enhanced Fc mediated effector functions in enhancing the efficacy of monoclonal antibodies to treat viral infections and inducing a protective response in animal models, using an oncological therapeutic approach and enhanced effector function in the treatment of infectious diseases, the vaccinal potential of specifically engineered antibodies in the treatment of chronic hepatitis B and SARS-CoV-2, and statements around the companys plans to explore the vaccinal potential of engineered antibodies as it advances through clinical development of VIR-3434 for the treatment of chronic hepatitis B and VIR-7832 for SARS-CoV-2. Many factors may cause differences between current expectations and actual results including unexpected safety or efficacy data observed during preclinical or clinical studies, challenges in treating chronic hepatitis B and neutralizing SARS-CoV-2, difficulty in collaborating with other companies or government agencies, and challenges in accessing manufacturing capacity. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Virs filings with theU.S. Securities and Exchange Commission, including the section titled Risk Factors contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

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Nature Publishes New Research from Vir Biotechnology Demonstrating the Capacity of Enhanced Monoclonal Antibodies to Induce Protective Adaptive...

Immunology

An Autoimmune-Like Antibody Response Has Been Linked With Severe COVID-19 – ScienceAlert

In the earliest days of the pandemic, many immunologists, including me, assumed that patients who produced high quantities of antibodies early in infection would be free from disease. We were wrong.

Several months into studying COVID-19, like other scientists, I've come to realize the picture is far more complicated. A recent research study published by my colleagues and me adds more evidence to the idea that in some patients, preventing dysregulated immune system responses may be as important as treating the virus itself.

I am an immunologist at Emory University working under the direction of Dr. Ignacio Sanz, Emory's chief of rheumatology. Immune dysregulation is our specialty.

A harrowing turn in the COVID-19 pandemic occurred with the realization that the immune system's power in fighting infection was sometimes pyrrhic.

In patients with severe COVID-19 infections, evidence emerged that the inflammatory process used to fight the SARS-CoV-2 virus were, in addition to fighting the virus, potentially responsible for harming the patient.

Clinical studies described so-called cytokine storms in which the immune system produced an overwhelming quantity of inflammatory molecules, antibodies triggering dangerous blood clots and inflammation of multiple organ systems, including blood vessels, in COVID-recovered children. All these were warning signs that in some patients, immune responses to the SARS-CoV-2 virus, which causes COVID-19, may have tipped from healing to destructive.

Quick thinking and courageous decisions made by physicians on the front lines led to the use of steroids, medicines that dampen the immune response, early on in the course of infection of hospitalized patients. This approach has saved lives.

But it's not yet clear what parts of the immune system physicians are dampening that is having the effect. Understanding the nature of immune dysregulation in COVID-19 could help identify patients in whom these treatments are most effective. It may even justify more targeted and powerful approaches for modulating the immune system currently reserved for autoimmune diseases.

Antibodies are powerful weapons. Produced by white blood cells called B cells, they latch onto infectious agents like viruses and bacteria and prevent them from infecting your healthy cells. These antibody-virus aggregates unleash powerful inflammatory reactions and serve as homing beacons that allow the rest of your immune system to target the pathogens efficiently. In some circumstances, they can even kill.

Antibodies are so powerful that cases of mistaken identity when a B cell produces antibodies that attack a person's own cells can lead to widespread organ damage and establish a perpetual cycle of immune self-targeting. We refer to this state of self-destruction as an autoimmune disease.

To avoid autoimmune disaster, and to ensure effective response against the invading pathogen, B cells undergo a training process. Those that respond to the virus refine their antibodies and mature, ensuring potent antibodies capable of disabling the invader. B cells that target your own tissue are destroyed.

But that maturation process takes time. Two weeks of B cell "training" during a severe infection can mean the difference between life and death. Faster antibody responses are needed.

To bridge that gap, the immune system has an alternative form of B cell activation called extrafollicular activation that generates fast-acting antibodies that seem to bypass many of the known safety checks that accompany a more precise response.

Extrafollicular responses develop quickly, are short-lived by design and die back when the more targeted responses emerge onto the scene.

Except when they don't.

Between 2015 and 2018, our lab found that these extrafollicular immune system responses were a common characteristic of people who suffered from autoimmune diseases, such as lupus.

Patients suffering from this disease show chronically active extrafollicular responses that led to high levels of self-targeted antibodies and destruction of organs such as the lungs, heart and kidneys.

The presence of specific kinds of B cells generated by extrafollicular responses in the blood can be an important indicator of disease severity in lupus, and now also COVID-19.

In a recently published paper, my colleagues and I have identified extrafollicular B cell signatures in cases of severe COVID-19 similar to those we saw in active lupus. We showed that early on in the response to infection, patients with severe disease undergo a rapid activation of this fast-track pathway for antibody production.

These patients produce high levels of viral-specific antibodies, some which are capable of neutralizing the virus. However, in addition to those protective antibodies, some that we saw look suspiciously like the ones found in autoimmune disorders such lupus.

In the end, patients with these autoimmune-like B cell responses fare poorly, with high incidences of systemic organ failure and death.

Let me be clear here: COVID-19 is not an autoimmune disorder. The autoimmune-like inflammatory responses my team discovered could simply reflect a "normal" response to a viral infection already out of hand.

However, even if this kind of response is 'normal', it doesn't mean that it's not dangerous. These prolonged extrafollicular responses have been shown to contribute to autoimmune disease severity both through the production of self-targeted antibodies and through inflammation that can damage tissue like the lung and kidney.

This suggests that these early immune responses to a viral infection like COVID-19 are in tension with the later-targeted antibody response; in other words, the body's rapid antibody production to nab the virus runs the risk of targeting not the virus, but the patient's own organs and tissues.

Immunologists like me need to learn more. Why are only some patients turning on such strong extrafollicular B cell responses? Are the antibodies that result from this response particularly prone to attacking and destroying the host's organs? Would an ongoing autoreactive response help explain instances of "lingering" COVID-19 even after the viral infection has cleared?

Despite these uncertainties, the medical community needs to recognize that, in the appropriate patients, dampening immune responses through steroid treatment (or perhaps even more powerful autoimmune-focused therapies) is a critical weapon in combating COVID-19.

Physicians and scientists must continue to build our arsenal of therapeutics around the idea that in some cases of COVID-19, controlling your response to the virus might be as important as controlling the virus itself.

Matthew Woodruff, Instructor, Lowance Center for Human Immunology, Emory University.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Biochemistry

CCM Professor’s Research to Assist with Finding Drugs to Combat Coronavirus Providing Maps of Virus Proteins for the World’s Scientific Community -…

RANDOLPH, NJ Professor Brian Olson, of the Department of Biology and Chemistry at County College of Morris (CCM), recently had his research on coronavirus targets published in the peer-reviewed Journal of Computer-Aided Molecular Design to assist with the development of drugs to combat the virus.

Olson, the lead author on the paper, worked with Dr. Tom Kurtzman of Lehman College to put together a team of researchers this past March when he realized how extensive the COVID-19 pandemic would become. In the paper,An Online Repository of Solvation Thermodynamic and Structural Maps of SARS-CoV-2 Targets, the researchers provide maps of water moleculeson the virus proteins that also are known as solvation maps. Olson explains that knowing which water molecules need to be displaced, and which do not, provides essential information to guide the development of drugs to treat COVID-19. The first step toward determining that is mapping where the water molecules are located on the proteins.

In March, Olson, who had been tracking the coronavirus on several databases, was certain COVID-19 would turn into a pandemic.

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We were seeing clusters on multiple continents and were unable to trace the sources of infection. It was clear this was going to be an immediate and international public health issue, he says. That compelled me to do something.

Utilizing the computational tool, GIST, developed by Kurtzman, the researchers worked from their homes during the pandemic. Prior to being published in the Journal of Computer-Aided Molecular Design, the research was posted by the team on Chemrxiv so it could be accessed early while the peer-review process was taking place.

Now that solvation maps of the COVID-19 virus are available, Olson and his team plan to use that information to search for new drugs. Making the information public and free also will aid others in their search for new and effective pharmaceuticals to defeat the coronavirus. According to Altmetrics Attention Score, which measures the online attention and activity of research papers, the work conducted by the Olson team ranks in the top 25 percent. Given that ranking, based on more than 2,200 views and over 300 downloads of the paper, Olson is encouraged about the development of drugs to fight the coronavirus.

I have never seen the international scientific community come together the way it has now to find some answers, says Olson. There is international collaboration and the sharing of information that previously would not have been shared.

Olson, who teaches forensic science at CCM, joined the colleges faculty in 2018. At CCM, he and several other professors, developed the colleges first virtual reality class to teach students forensic science skills by analyzing murder scenes. Along with his work on the coronavirus, he is researching the development of pain killers to replace opiates.

Olson earned his associate degree in science from the Borough of Manhattan Community College, his bachelors in biochemistry from Hunter College, his masters in biochemistry from the City University of New York (CUNY) Graduate Center, and is working on his doctorate in biochemistry from CUNY Graduate Center.

He is a strong advocate for community colleges, and CCM in particular. Community colleges place a high value on quality teaching, he says. I am so fortunate. I have fun researching tiny molecules and on top of that I get paid to talk to students about narcotics, murders and other fascinating topics. I cant imagine having a better job.

# # #

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Biochemistry

Scientists zoom in on HIV inside a test tube, find critical steps in infection – Live Science

Scientists have finally recreated the initial steps of HIV infection in a test tube, offering an incredibly zoomed-in view of the virus in action.

The amazing images show a cone-shaped shell of geometric tiles, called the capsid, that sits at the virus's center and contains its genetic material, known as RNA. Before infiltrating a cell, the capsid is surrounded by an envelope of fatty molecules; this envelope fuses to the host cell to let the capsid inside, where it then carries the RNA to the cell's nucleus. On the way, the RNA replicates, and once inside the nucleus, it invades the host's DNA.

By granting a closer look at this replication process, the new study highlights that the capsid itself plays a critical role in infection and that specific criteria must be met for the virus to interweave its genome with the host cell's.

Knowing how to recreate the initial steps of HIV infection "means we have many more tools for dissecting the process of replication," said study author Wesley Sundquist, a distinguished professor of biochemistry at University of Utah Health. In particular, the study, published Oct. 8 in the journal Science, describes a cell-free system that can be used to study how HIV invades the host genome such a system could "revolutionize HIV experiments in many labs," Leo James, a group leader at the MRC Laboratory of Molecular Biology, who was not involved in the study, told Live Science in an email.

"To have accomplished all this is a real tour de force," James said. Beyond basic research, the system could also help explain how experimental drugs that target the capsid work to limit HIV replication, Sundquist said in a statement.

Related: 12 amazing images in medicine

Although the test tube experiments capture aspects of HIV infection in superb detail, they cannot recreate every step in the process, Sundquist noted. Infection typically starts when the outer membrane of the virus fuses with the membrane of a host cell, allowing the capsid and its innards to sneak inside. But with a cell-free system, the authors had to bypass this initial step.

They instead used a compound found in bee venom, called melittin, to "permeabilize" the viral membrane and release the capsid held within.

The HIV capsid has tiny pores in it, and normally, as a virus particle floats through a human cell's cytoplasm, it picks up the cellular building blocks of DNA, called deoxynucleotide triphosphates, that are already there, according to a 2017 report in the journal Nature. As it travels to the nucleus, the virus particle uses those building blocks to make copies of full strands of DNA, thanks to a special enzyme housed inside the capsid. This is how the virus copies its genetic material to later insert into the host genome. How the virus "knows" when to start this so-called reverse transcription is still somewhat mysterious, but studies hint that biochemical properties of the host cell act as cues for the reaction to begin.

But a test tube doesn't automatically have DNA building blocks in solution, so to jumpstart reverse transcription, the authors added them. "This method has been around for a while, but it's tricky to get the reaction to go until completion," James noted. But the study authors managed to get reverse transcription running smoothly; to do so, they learned that the capsid must stay mostly intact throughout the process.

Related: Going viral: 6 new findings about viruses

"The capsid has to be largely intact, and it has to be of the proper stability or flexibility, to support reverse transcription," meaning the capsid must be bound tightly enough to not fall apart during reverse transcription, but able to open up when the capsid enters the nucleus, in order to unleash its copied DNA, Sundquist said. Fortunately, scientists recently discovered a way to keep the capsid just stable enough.

Study author Owen Pornillos, an associate professor of molecular physiology and biological physics at the University of Virginia, and his colleagues found that a compound called IP6 binds to the capsid's tiled surface, they reported in 2018 in the journal Nature. IP6 carries a negative charge, while each tile carries a positive charge on the side that points in toward the center of the capsid; since opposites attract, when IP6 binds to the capsid, it helps pull the tiles into a tighter, more stable arrangement.

"Before the discovery of IP6, someone would remove the [viral] envelope in vitro and everything would fall apart and they could not see anything," said Joo Mamede, an assistant professor in the Department of Microbial Pathogens and Immunity at Rush University, who was not involved in the study.

IP6 is "quite abundant" in cells, so in their test tube experiments, the authors added similar concentrations of the compound as would be found in cells, Sundquist said. "That was really the trick," he added. "Until we knew it, we were working with capsids that were far too unstable."

Using computer models of molecules and an electron microscope, the authors could literally see that the 240 tiles making up the capsid held their lattice-like structure stable throughout reverse transcription. As the DNA strands grew larger, their ends sometimes poked through tiny gaps in the lattice weave, the authors noted, and sometimes singular tiles could be seen dislodging while the rest of the capsid stayed intact.

The capsid may need to stay stable to keep the RNA and transcribing enzyme close to each other, said Christopher Aiken, a professor of pathology, microbiology and immunology at Vanderbilt University, who was not involved in the study. The enzyme tends to fall off the RNA during transcription, so "by keeping the enzyme contained, it can rebind the template and continue DNA synthesis," Aiken told Live Science in an email.

With reverse transcription complete, the authors then moved on to the next step in infection: integration, where the viral DNA infiltrates the host genome. They introduced DNA strands known as plasmids into their test tubes, to serve as proxies for the DNA in a human nucleus, but integration would not begin without an additional ingredient. Only "whole cell extracts," a mix of proteins and molecules drawn from cells, would allow the viral DNA to pervade the plasmids.

In the future, the team hopes to pinpoint precisely which ingredients in the cell extracts trigger integration, Sundquist said. "It's likely to be more than one thing," he noted. One challenge is that, in test tube experiments, "it's always difficult to know if you're missing something," he said.

Related: The 12 deadliest viruses on Earth

One limitation of the study is that it can't perfectly recreate cellular conditions, James said.

"Any in vitro system, however powerful, can only be used to test the components we know about and can add into the reaction," James said. For instance, in actual cells, the capsid must travel to the cell nucleus, where the DNA is held, and then slip through portals known as the nuclear pores. There may be unknown factors that alter the capsid during this journey, Sundquist noted.

That said, the new cell-free system could help reveal the identity of those unknown factors, Mamede added. Scientists can now make observations in a cell-free environment and then check to see if the same behavior appears in actual cells, he said.

In addition, the system could be useful in drug development. "You can test [new drugs] more readily with one of these simplified systems than with a cell," Mamede told Live Science. "This way, you can see mechanistically what it's really doing to the virus."

The pharmaceutical company Gilead Sciences currently has a new drug in human trials that targets the HIV capsid specifically, according to ClinicalTrials.gov. Based on early data, the drug appears to alter the capsid at various points of infection, including during reverse transcription. Sundquist said that the cell-free study underscores that the capsid is a "critical component" of HIV infection, and that corrupting the capsid can limit the virus's ability to multiply.

Originally published on Live Science.

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Scientists zoom in on HIV inside a test tube, find critical steps in infection - Live Science