Category Archives: Cell Biology

Cell Biology

How long can COVID-19 live on surfaces? – The Hub at Johns Hopkins

BySamuel Volkin

According to a recent study published in the New England Journal of Medicine, SARS-CoV-2, the virus that causes COVID-19, can live in the air and on surfaces between several hours and several days. The study found that the virus is viable for up to 72 hours on plastics, 48 hours on stainless steel, 24 hours on cardboard, and 4 hours on copper. It is also detectable in the air for three hours.

Carolyn Machamer, a professor of cell biology whose lab at the Johns Hopkins School of Medicine has studied the basic biology of coronaviruses for years, joined Johns Hopkins MPH/MBA candidate Samuel Volkin for a brief discussion of these findings and what they mean for efforts to protect against spread of the virus. The conversation has been edited for length and clarity.

Machamer: What's getting a lot of press and is presented out of context is that the virus can last on plastic for 72 hourswhich sounds really scary. But what's more important is the amount of the virus that remains. It's less than 0.1% of the starting virus material. Infection is theoretically possible but unlikely at the levels remaining after a few days. People need to know this.

What you need to know

Resources and updates for the Johns Hopkins community, including travel guidance, information on university operations, and tips for preventing the spread of illness

While the New England Journal of Medicine study found that the COVID virus can be detected in the air for 3 hours, in nature, respiratory droplets sink to the ground faster than the aerosols produced in this study. The experimental aerosols used in labs are smaller than what comes out of a cough or sneeze, so they remain in the air at face-level longer than heavier particles would in nature.

You are more likely to catch the infection through the air if you are next to someone infected than off of a surface. Cleaning surfaces with disinfectant or soap is very effective because once the oily surface coat of the virus is disabled, there is no way the virus can infect a host cell. However, there cannot be an overabundance of caution. Nothing like this has ever happened before.

The CDC guidelines on how to protect yourself include:

Coverage of how the COVID-19 pandemic is affecting operations at JHU and how Hopkins experts and scientists are responding to the outbreak

There is no evidence one way or the other. The virus's viability in exposure to heat or cold has not been studied. But it does bear pointing out that the New England Journal of Medicine study was performed at about room temperature, 21-23 degrees Celsius.

SARS-CoV-2 behaves like a typical respiratory coronavirus in the basic mechanisms of infection and replication. But several mutations allow it to bind tighter to its host receptor and increase its transmissibility, which is thought to make it more infectious.

The New England Journal of Medicine study suggests that the stability of SARS-CoV-2 is very similar to that of SARS-CoV1, the virus that caused the 2002-2003 SARS global outbreak. But, researchers believe people can carry high viral loads of the SARS-CoV-2 in the upper respiratory tract without recognizing any symptoms, allowing them to shed and transmit the virus while asymptomatic.

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How long can COVID-19 live on surfaces? - The Hub at Johns Hopkins

Cell Biology

Study reveals major changes that occur in mammalian skin cells during wound healing – The Medical News

Reviewed by Emily Henderson, B.Sc.Mar 19 2020

A team of University of California, Irvine researchers have published the first comprehensive overview of the major changes that occur in mammalian skin cells as they prepare to heal wounds. Results from the study provide a blueprint for future investigation into pathological conditions associated with poor wound healing, such as in diabetic patients.

This study is the first comprehensive dissection of the major changes in cellular heterogeneity from a normal state to wound healing in skin."

Xing Dai, PhD, professor of biological chemistry and dermatology in the UCI School of Medicine, and senior author

This work also showcases the collaborative efforts between biologists, mathematician and physicists at UCI, with support from the National Institute of Arthritis & Musculoskeletal & Skin Diseases-funded UCI Skin Biology Resource-based Center and the NSF-Simons Center for Multiscale Cell Fate Research.

The study, titled, "Defining epidermal basal cell states during skin homeostasis and wound healing using single-cell transcriptomics," was published this week in Cell Reports.

"Our research uncovered at least four distinct transcriptional states in the epidermal basal layer as part of a 'hierarchical-lineage' model of the epidermal homeostasis, or stable state of the skin, clarifying a long-term debate in the skin stem cell field," said Dai.

Using single-cell RNA sequencing coupled with RNAScope and fluorescence lifetime imaging, the team identified three non-proliferative and one proliferative basal cell state in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization, which is the process by which the skin and mucous membranes replace superficial epithelial cells damaged or lost in a wound.

Epithelial tissue maintenance is driven by resident stem cells, the proliferation and differentiation dynamics of which need to be tailored to the tissue's homeostatic and regenerative needs. However, our understanding of tissue-specific cellular dynamics in vivo at single-cell and tissue scales is often very limited.

"Our study lays a foundation for future investigation into the adult epidermis, specifically how the skin is maintained and how it can robustly regenerate itself upon injury," said Dai.

Source:

Journal reference:

Haensel, D., et al. (2020) Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics. Cell Reports. doi.org/10.1016/j.celrep.2020.02.091.

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Study reveals major changes that occur in mammalian skin cells during wound healing - The Medical News

Cell Biology

Organ-Chips provide human-relevant insights into diseases and toxicity mechanisms – The Medical News

Organs-on-Chips technology has entered the mainstream and has reached 150 installations for use by researchers across many industries, including 10 of the top 25 biopharmaceutical companies, as well as leading international academic research centers and U.S. government laboratories, including the U.S. FDA through a collaborative agreement and the U.S. Army.

Organ-Chips that are currently available for use in the lab-ready platform developed by Emulate, Inc., include the Liver-Chip, Kidney-Chip, and new Intestine-Chip, launched commercially earlier this year. Ongoing R&D is supporting the development of additional Organ-Chips, such as the Brain-Chip, and new applications in key areas of biology and diseases, including applications in neurodegenerative disease, gastrointestinal diseases, and infectious diseases, such as COVID-19.

Combining biology and microengineering, Organ-Chips contain tiny hollow channels lined with tens of thousands of living human cells and tissues and can be used to predict human response. For early adopters conducting R&D related to drug discovery and development, the Organ-Chip platform provides human-relevant insights and answers to the complex questions required for disease modeling, target validation, and safety assessment in drug development.

Researchers can culture the chips--including the Liver-Chip, Kidney-Chip, and Intestine-Chip--using Emulate's portfolio of protocols, enabling research to understand how the human body responds to disease, medicines, chemicals, and foods. The lab-ready platform - including the Zo Culture Module, Organ-Chips, and application tools - recreates key factors of the body's dynamic cellular microenvironment, including tissue-to-tissue interfaces, fluid flow, and mechanical forces.

The lab-ready platform enables researchers with no prior experience with Organs-on-Chips to conduct studies, using the platform's supporting protocols and software to collect, analyze, and share data. This platform integrates into the workflows of researchers developing new drugs and products, providing human-relevant mechanistic data on toxicity and diseases that researchers can use to assess safety risks and make informed, efficient decisions throughout the drug discovery and development process.

We are excited to see researchers in industry, government, and academia use our Organs-on-Chips platform for a range of applications, including human-relevant disease modeling and studies to gain insights related to new drug modalities and disease mechanisms that are not feasible with conventional animal models or cell cultures. Organs-on-Chips technology provides a window into the inner workings of human biology and disease, and by putting the technology in the hands of researchers, we are changing the way medications and products are evaluated to help improve human health and bring new cures to patients."

Geraldine A. Hamilton, President and Chief Scientific Officer of Emulate, Inc

Emulate's platform is comprised of the following key components:

Emulate's lab-ready platform has its origins in a $37 million grant from the Defense Advanced Research Projects Agency (DARPA) in 2012 to the Wyss Institute for Biologically Inspired Engineering at Harvard University to create Organs-on-Chips to study complex human physiology outside the body. This foundational research enabled the development of chips with a level of human-relevant biological complexity not feasible with conventional cell-based systems, as well as instrumentation designed to enable any researcher to use the technology in their laboratories. Based on the success of this early research, Harvard established a worldwide license agreement to form the start-up company, Emulate, and the company became operational in January 2015. The Emulate team accelerated development of Organs-on-Chips technology to create the platform that is now commercially available, working with an extensive community of collaborators across industry, academia, and government agencies.

In addition to applications in drug discovery and development, Emulate's platform can be used in other industries, including cosmetics, food, chemical-based consumer products, and personalized health, to enable new understanding of human response to products.

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Organ-Chips provide human-relevant insights into diseases and toxicity mechanisms - The Medical News

Cell Biology

Understanding the Brain in High-Definition: Rapid, Automatic Identification of Individual, Live Brain Cells – SciTechDaily

Nerve cells are shaped like young plants: big round seeds (cell bodies) surrounded by a nest of frizzy roots in one direction (dendrites) and a single long stem stretching out in the other direction (axon). This image shows variations in the location of some neuron cell bodies between different animals as ellipses. Each neuron is randomly colored. Neurons are arranged top-to-bottom and left-to-right in the graph as they are located nose-to-tail (anterior-posterior) and back-to-belly (dorsal-ventral) in a worm. Credit: Toyoshima et al., 2020, DOI: 10.1186/s12915-020-0745-2, CC BY-ND 4.0

Researchers working towards understanding the brain in high-definition, single-cell level of detail have designed a new computer program to identify each nerve cell in fluorescent microscope images of living worms. Previous attempts to automate the identification of individual nerve cells have been thwarted by the fact that the same cell can be in vastly different locations in different worms.

The worms areC. elegans, tiny roundworms common in soil and research labs around the world. Each of the 959 cells in the animals transparent, 1 millimeter-long bodies has been identified, named and mapped, including their 302 nerve cells.

Scientists completed the first map of theC. elegansnervous system in 1986 and have been improving it ever since. More recent projects include OpenWorm, an ongoing global effort to design a cell-by-cell and behaviorally accurate virtualC. elegans a research-worthy version of a Tamagotchi pet.

The central DNA-containing cell bodies of C. elegans neurons are shown with the three fluorescent colors used in the genetically modified strain of C. elegans developed by the research team. Note how neighboring cells are different colors. Successfully annotated neurons are labeled with letters and cells whose identity could not be annotated are labeled with numbers. Not all 302 C. elegans neurons are present in this image. Credit: Toyoshima et al., 2020, DOI: 10.1186/s12915-020-0745-2, CC BY-ND 4.0

Despite their value, generalized brain atlases, so-called connectome maps, are still no help for identifying neurons in individual, live, wriggling worms.

Imagine if you knew the names of all the cities on a map, but the cities moved each time you looked. That is what its like, trying to compare current brain atlases to living organisms, said Professor Yuichi Iino from the University of Tokyo, co-last author of the recent research paper published in BMC Biology.

Iinos research group wants to identify and map each nerve cell in livingC. elegansso that they can chart the pathways of electrical impulses that make behaviors, learning and memory possible.

C. elegans brain neurons are not trapped in a skull, but just form a loosely packed group of 150 neurons in the head region of the animal.

The neurons are tiny, and in the head ofC. elegans they are surrounding this large bulb thats part of the digestive system, so they get pushed and pulled around a lot as the animal moves or eats, explained Iino.

Researchers began by finding unique combinations of genes that, when artificially attached to fluorescent protein tags, would cause 35 different small groups of neurons to glow under a microscope.

These new genetically modified strains ofC. elegansmade all of the researchers subsequent image studies and computer programming work possible.

Researchers identified individual neurons in 311 worms in total, about 10 worms for each of the 35 neuron groups, and measured the distances and relative positions between pairs of neurons in the microscopy images.

Although neurons were known to shift within each worm, no one expected the neurons to have different home base locations in different individuals. The positions of the central cell body of some neurons can vary by more than 0.02 millimeter between different animals, a significant distance for an animal only 1-millimeter long.

IndividualC. elegansare thought to be uniform because they all have almost the same cell lineages and a stereotyped neural circuit. It was really surprising, though, how large the positional differences are between individual animals, said Assistant Professor Yu Toyoshima, a co-first author of the recent research paper and member of the Iino lab.

The research team then used their new position variation data and theC. elegansconnectome brain atlas to develop a computer program to automatically identify neurons. The program uses a mathematical algorithm to analyze a microscopy image of theC. elegansbrain and assign the statistically most likely identity to each neuron based on that neurons position in relation to other neurons.

The algorithm is only 60 percent accurate, which is too low for fully automatic cell identification, but it speeds up our work enough to make other projects possible to understand neural networks based on whole-brain imaging data, said Toyoshima.

Part of what made this project possible inC. elegansis that every neuron was already known and named. Using a similar technique in other animals would require fine-tuned genetic manipulation to cause groups of neurons to glow under a microscope and knowing how many neurons need to be identified.

The human brain has billions of neurons, so understanding our own brains at the single-cell level would be extremely difficult.C. eleganshave small brains, but they can still learn and change behaviors, so they could allow us to understand how networks of neurons create behavior, said Iino.

Reference: Neuron ID dataset facilitates neuronal annotation for whole-brain activity imaging ofC. elegans by Yu Toyoshima, Stephen Wu, Manami Kanamori, Hirofumi Sato, Moon Sun Jang, Suzu Oe, Yuko Murakami, Takayuki Teramoto, Chanhyun Park, Yuishi Iwasaki, Takeshi Ishihara, Ryo Yoshida and Yuichi Iino, 19 March 2020, BMC Biology.DOI: 10.1186/s12915-020-0745-2

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Understanding the Brain in High-Definition: Rapid, Automatic Identification of Individual, Live Brain Cells - SciTechDaily

Cell Biology

Smoking or Vaping May Increase the Risk of a Severe Coronavirus Infection – Scientific American

Smoking or vaping could make you more vulnerable to a severe infection with the novel coronavirus, some experts say.

Although there have not been many studies investigating this link specifically, a wealth of evidence suggests that smoking suppresses immune function in the lungs and triggers inflammation. There have been far fewer investigations of vaping, but preliminary research suggests it may do similar damage. And both long-term smokers and e-cigarette users are at a heightened risk of developing chronic lung conditions, which have been associated with more severe cases of COVID-19, as the disease caused by the new virus is called. Scientists say it therefore seems reasonable to assume that smokingand possibly vapingcould increase the risk of developing a serious infection from the coronavirus.

All these things make me believe that we are going to have more severe casesespecially [in] people who are [long-term] smokers or vapers, says Melodi Pirzada, chief of pediatric pulmonology at NYU Winthrop Hospital on Long Island.* She has not treated COVID-19 patients herself, but it is definitely common sense to think that once you have a history of smoking or vaping, the whole airways, the defense mechanism of your lungseverything changes, she says.

Very little research has looked directly at whether smoking or vaping increases a persons risk of severe COVID-19. A preprint study in China found that men were slightly more likely than women to be hospitalized for coronavirus infections, and scientists say this observation could be related to the fact that in the country, vastly more men than women smoke. (The paper, which has not been peer-reviewed, has been withdrawn because it was based on early data. It will be replaced with a more up-to-date version soon, the authors write.) Another study, which has been published online in the Chinese Medical Journal, involved 78 patients with COVID-19 and found that those with a history of smoking had a 14 percent higher risk of developing pneumonia.

There is substantial scientific literature showing that smoking inflames the lungs and suppresses immune function. For regular smoking, we know it inhibits the ciliary clearance of the airways, Pirzada says. We have these little [hairlike] structures known as cilia, and they are responsible for taking the toxins and the mucus out of our airways and clearing the lungs when we cough. We know that that is affected when you smoke and when you vape.

During a respiratory infection in the lungs, there tends to be an influx of white blood cells called neutrophilsthe first responders that start killing the pathogenfollowed by an influx of lymphocyteswhich are responsible for clearing the infection. Theres a very coordinated series of events that take place when you do become infected with a virus, says Ray Pickles, an associate professor of microbiology and immunology at the University of North Carolina at Chapel Hill. These are probably the events that take place in the vast majority of us as individuals, whether were infected by influenza or whether were infected by SARS-CoV-2, as the new coronavirus is known. I think once you start perturbing this sequence of events in any which way or direction, thats when things can go awry.

Smoking is a known risk factor for influenza, says Robert Tarran, a professor of cell biology and physiology at Chapel Hill. People who smoke are immunosuppressed to some degree, Tarran says. They make more mucus. It doesnt clear the lungs as well. There are pro-inflammatory changes; immune cells are changed as well. And all that leads up to, basically, theyre more likely to get viruses and have a worse outcome.

Vapers risk of viral infections has not been studied much, although there are some epidemiological studies suggesting they are more likely to get respiratory infections, Tarran says. And animal studies provide some clues. Mice that were exposed to e-cigarette aerosol and then inoculated with Streptococcus pneumoniaebacteria or influenza A were less likely to survive. And vaping may interfere with neutrophil function, some studies suggest. Scientists at Chapel Hill have shown that e-cigarette use suppresses the activity of immune- and inflammatory-response genes in nasal cellsmore so even than smoking. And a preprint study found that the gene that encodes the receptor ACE2, which the novel coronavirus uses to infect cells, is more active in smokers than nonsmokers.

Of course, none of these studies directly show that smoking or vaping increases the severity of COVID-19 infections; it is not clear to what extent they can be extrapolated to the current pandemic. But given that smoking and vaping do well-established harm to the immune system, it seems prudent to assume they might make coronavirus infections worse.

I think that a sensible thing to do for people is to stop smoking and stop vapingand avoid secondhand exposure, says Stanton Glantz, director of the Center for Tobacco Control Research and Education at the University of California, San Francisco. We dont have every little detail on this nailed down, he says. But based on what we know, generally, about smoking and e-cigarettesand in particular about smoking and COVID-19 from people who are already sick, from one study in Chinait stands to reason that you would lower your risk if you stopped doing these things. After all, Glantz adds, whats the downside?

*Editors Note (3/17/20): Thissentencewaseditedafter posting toupdateMelodi Pirzadas title.

Read more about the coronavirus outbreakhere.

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Smoking or Vaping May Increase the Risk of a Severe Coronavirus Infection - Scientific American

Cell Biology

University restricts research in effort to prevent COVID-19 spread – The Brown Daily Herald

While people turn to scientists for the latest updates on COVID-19, laboratories across campus will more or less go dark after 5 pm today. The constant hum of machines mixing samples will grow quiet as equipment is shut off, new experiments are canceled and entry is limited to essential personnel only.

The decision to ramp down research efforts was released March 15th in a message from Provost Richard Locke P 18 and Vice President for Research Jill Pipher that was posted on Browns COVID-19 website.

The ramping down of research laboratories is in support of social distancing to smooth the curve of expected COVID-19 cases and the potential to overwhelm our local healthcare system which has limited resources, Director of Browns Environmental Health and Safety Stephen Morin wrote in an email to The Herald.

As the University increased efforts across the board to stop the spread of COVID-19, by Sunday, it became pretty clear that we would be going into a completely different mode and everything would be conducted remotely, said Mark Johnson, Royce family associate professor of teaching excellence, associate professor of biology and director for the molecular biology, cell biology and biochemistry graduate program.

My sense is that everybody really wants to cooperate. Everyone appreciates the leadership of the Provost on this and is doing their best to comply, Johnson said.

Laboratories and research in general are a vital function of Brown University and it takes a campus community to support their operations, Morin wrote. He added that many groups ranging from faculty to student researchers, as well as facilities management, environmental health and safety staff and administrative personnel, are crucial for the everyday work of laboratories on campus.

It could be a risk to all these groups to allow them to continue under normal operations, Morin wrote.

Only those who need to enter for critical work will have access to laboratory buildings, Morin wrote. Examples of critical work include equipment maintenance such as preservation (or) maintenance of cell lines, changing out gas tanks or cryogens, filters and water checks.

Animals that are currently maintained as research subjects will also receive continued veterinary care, Morin wrote.

Labs working with bacteria and other cells are able to preserve the organisms grown for their experiments through cryogenic storage the process of freezing cells in liquid nitrogen. But for labs reliant on more complex living organisms, the solution is not so simple.

Among the University faculty winding down their research this week is Assistant Professor of Molecular Microbiology and Immunology Shipra Vaishnava, who uses mice at the Universitys Biomedical Center to investigate how diet and bacteria in the gut impact immunity against infections and diseases. The mice are kept in a gnotobiotic mouse facility in a germ-free environment. These now paused long-term studies require mice to be bred for months, prompting researchers to reduce their mouse populations and cryo-preserve the sperm of their mouse lines for propagation whenever research can resume. Weve lost a lot of time that weve already invested in these experiments, so anywhere between three to six months, she said.

Many labs typically have teams of researchers conducting experiments from early morning until late evening, including many weekends. This level of activity has already dropped significantly due to COVID-19 concerns. Aside from the scurry of mice, the only other source of movement in the Vaishnava Lab will now be from the two essential personnel at a time looking after the labs animals for only two to three hours each week.

Critical work that is permitted to continue also includes work whose interruption would result in irretrievable or unrecoverable loss of data or samples, or loss of time for an ongoing experiment that could not be recovered within a reasonable period, Vice President for Research Jill Pipher wrote in a statement to The Herald.

Pipher added that Brown is carefully reviewing, on a case-by-case basis, every request to continue critical work.

In early March, Johnsons lab began a new study on the relationship between temperature and plant production. Following the new restrictions,the laboratory-based components of the project will be put on hold. But he is grateful that the lab collected a data set a couple weeks ago that they can now analyze remotely.

In a way projects dont really have beginnings and ends. There are always new things that you want to try in the lab, Johnson said. Now that labs are being closed, its hard to sort of wrap your head around the idea that you cant do that.

The closure of the labs is also impacting research trainees, including undergraduate, graduate and postdoctoral students, who cannot continue their work away from the lab bench. Undergraduate students were asked to leave campus by Tuesday evening, The Herald previously reported.

Vaishnava had undergraduate students doing for-credit research in her lab. For the rest of the semester, she said they will have to instead concentrate on readings, discussions and designing future experiments. Graduate students timelines to collect data and finish their research papers may now have to shift, and postdoctoral students can no longer attend the workshops and conferences that were important parts of their education, Vaishnava said.

The interruption of experiments delays publication of their own findings which factors into researchers career promotions. But Vaishnava hopes since this is such a worldwide, global phenomenon, there would be a mindfulness about it.

Samuel Rasche GS, a second-year masters student in the Laboratory for Cognitive and Perceptual Learning and a visiting research fellow from the University of Amsterdam, has also had to pause his work because of necessary restrictions on human subjects research. His research depends on people who attend numerous sessions involving a series of complex tasks that they could not perform remotely on their own.

Similar to Vaishnavas lab, researchers working in the same lab as Rasche are practicing social distancing by not permitting more than one person to be in a room at the same time, Rasche said.

For now, Rasche plans to stay in Providence. The University of Amsterdam has not yet requested that he return home, but a lot of other students and supervisors I know that are from abroad went back (home), so that kind of pressures me too to go back, he said.

I just try to stay positive and productive, Rasche said. Its a sad situation because I also met a lot of people here and literally everybody left. Its a big change.

Sarah Berman 20.5 said that the decision for research to shut down made the transition of leaving campus easier. Honestly, if the lab had stayed open, I would have stayed. If labs are able to reopen for student research during the semester, Im absolutely coming back, she said. She is able to do some remote work at home on the project that will become her thesis in the fall.

Researchers have also lost time needed to train students. We have lost this overlap period of a couple of months that is critical for passing down skills and materials and samples from graduating researchers to those still in the lab who would be taking over the projects, Vaishnava said.

With the global, national and state-wide situation surrounding COVID-19 rapidly changing, the current protocols are also subject to change. The University will continue to monitor and re-evaluate the situation, issuing updates and guidance for researchers as often as necessary, Pipher wrote.

While the context of COVID-19 is unprecedented, EH and S has previously worked to safely close laboratories in the event that a professor left the University or in the case of renovation. This week they developed a set of guidelines for researchers to follow to assist researchers in thinking about the steps to be taken to safely close the space temporarily.

COVID-19 is a serious public health issue, and we all have to do our part. As scientists, we should understand this more than anyone else why these steps are needed, Vaishnava said. Its hard, but I think its something we need to do.

The health and safety of the research community is our top priority, Pipher wrote.

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University restricts research in effort to prevent COVID-19 spread - The Brown Daily Herald

Cell Biology

Blocking sugar structures on viruses and tumor cells – Biophotonics.World

Prof. Skerra's current research findings are paving the way for the development of new types of binding proteins for biological sugar structures, which play a significant role in cancer as well as infectious diseases. - What you can see here: A model sugar ligand (yellow) binds to the boric acid group (green) in the pocket of a binding protein (pink).

Image source: TUM-Chair of Biological Chemistry

The laboratory directed by Arne Skerra, Professor of Biological Chemistry, has its focus on designing artificial binding proteins for therapeutic applications. The laboratory's current research findings are paving the way for the development of new types of binding proteins for biological sugar structures, which play a significant role in cancer as well as infectious diseases.

Recognizing biological sugar structures

"The recognition of specific sugar molecules, or so-called carbohydrates, is of vital importance in many biological processes," Prof. Skerra explains. Most cells carry a marker consisting of sugar chains which are attached to the outside of the cell membrane or to the membrane proteins, thus enabling the body to identify where these cells belong or whether certain cells are alien. Pathogens also have sugar structures of their own, or they can bind to these.

Proteins, which perform a wide range of functions within cells, generally have only low affinity to sugars. Thus, their molecular recognition poses a challenge. The reason: water molecules look similar to the sugar molecules, meaning that they are basically hidden in the aqueous environment of the cells. Prof. Skerra's research group therefore set out to design an artificial binding protein with a peculiar chemical composition which makes it easier to bind to biological sugar structures.

A boric acid group implemented into a protein as amino acid

Amino acids are the building blocks of proteins. As a rule, nature only uses 20 amino acids in all living organisms. "Using the possibilities opened up by synthetic biology, we have employed an additional artificial amino acid," reports researcher Carina A. Sommer.

"We have succeeded in incorporating a boric acid group, which exerts intrinsic affinity to sugar molecules, into the amino acid chain of a protein. In doing this, we have created an entirely new class of binding protein for sugar molecules," Sommer explains. This artificial sugar-binding function is superior to natural binding proteins (so-called lectins) both in strength and with regard to possible sugar specificities.

"The sugar-binding activity of boric acid and its derivatives has been known for nearly a century," says Prof. Skerra. "The chemical element boron is common on earth and has low toxicity, but so far has largely remained unexplored by organisms."

"By using X-ray crystallography, we have succeeded in unraveling the crystal structure of a model complex of this artificial protein, which allowed us to validate our biomolecular concept," explains scientist Dr. Andreas Eichinger.

The next step: towards medical application

Following approximately five years of fundamental scientific research, the findings from Prof. Skerra's laboratory can now be applied to practical medical needs. Prof. Skerra points out: "Our results should not only be used to support the future development of new carbohydrate ligands in biological chemistry, but should also pave the way for creating high-affinity agents for controlling or blocking medically-relevant sugar structures on cell surfaces."

Such a "blocking agent" could be used for conditions in which strong cell growth is evident or when pathogens are attaching themselves to cells, for example in oncology and virology. If we are successful in blocking the sugar-binding function and in slowing down the progress of a disease, this would give the patient's immune system sufficient time to mobilize the body's natural defense.

Source: Technical University of Munich

Related journal article:http://dx.doi.org/10.1002/cbic.201900405

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Blocking sugar structures on viruses and tumor cells - Biophotonics.World

Cell Biology

Singapore researchers find common therapeutic vulnerability for a deadly blood cancer – The Medical News

Reviewed by Emily Henderson, B.Sc.Mar 18 2020

CML is a blood cancer that can be controlled by continuously taking an expensive type of medicine called a tyrosine kinase inhibitor (TKI). In almost all patients, stopping TKI treatment results in recurrence of CML. While most CML patients respond well to life-long TKI usage, about 10 per cent of patients become resistant to TKIs, and progress to late-stage or blast crisis (BC) CML. Patients with BC almost always die from their disease. While many genetic mutations are known to be associated with BC progression, the mechanisms by which they and other factors cause BC remain largely unknown. This knowledge gap prevents clinicians from identifying which CML patients are at risk of BC progression, and treating BC when it occurs.

To fill these critical gaps, we employed the latest molecular approaches to establish that the so-called 'polycomb repressive complex', or PRC, alters the regulation of a set of genes which drive BC progression. We found that the consequences of altered PRC activity were common to the majority of BC cases, regardless of the different leukemia-causing mutations we also found in them."

Dr. Tun Kiat Ko, Research Fellow at Duke-NUS' Cancer and Stem Cell Biology (CSCB) program

Using this increased understanding, the team devised novel drug combinations, which reverse the downstream effects of the PRC in BC. At the same time, they also developed methods to identify CML patients who were at increased risk of developing TKI-resistance and progressing to BC.

"Our discovery is like finding the 'one ring that rules them all'. Since there are many cancer-causing genetic mutations that occur when chronic phase CML transforms to blast crisis, it has been very challenging to determine which ones are critical to BC, and therefore important to target. By discovering this 'one ring' and how to 'destroy' it with a novel drug combination, we open the door to treating this deadly cancer with the same combination of drugs regardless of the myriad mutations that exist in any particular patient. In addition, our study demonstrates the ability of scientists and clinicians to make exciting discoveries that can be translated to the improved health of patients all over the world, as well as Singaporeans," said Associate Professor Ong Sin Tiong from the Duke-NUS CSCB programme and corresponding author of this study.

"The multi-omics approach was critical to the success of the study. Each layer of information provided us corroborative evidence and insight into the dysfunction of the polycomb repressive complex leading to the progression to blast crisis stage of CML," asserted Asif Javed, co-corresponding author of the study.

"This study is another example of how interdisciplinary research leads to new insight," says Axel Hillmer, Group Leader at the GIS who led the genomics part of the project.

Patrick Tan, Executive Director of GIS, adds, "Due to technology advancements over the last years, it is now possible to apply more complex genomic analyses to translate such findings into routine diagnostics."

"As a hematologist treating patients with advanced blast crisis CML, it is disheartening when we run out of treatment options for them. And that is why we are very encouraged by the study findings and certainly hopeful that our patients may one day benefit from the efforts of our collaboration," Associate Professor Charles Chuah, Senior Consultant, Department of Haematology, SGH.

The team is currently working on approaches to identify CML patients who are at risk of BC transformation, and also to determine why the key PRC-related events occur in the first place.

Source:

Journal reference:

Ko, T.K., et al. (2020) An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia. Blood. doi.org/10.1182/blood.2020004834.

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Singapore researchers find common therapeutic vulnerability for a deadly blood cancer - The Medical News

Cell Biology

Hebrew University to Collaborate with Cytovia Therapeutics – GlobeNewswire

NEW YORK and JERUSALEM, March 18, 2020 (GLOBE NEWSWIRE) -- Yissum, the technology transfer company of The Hebrew University of Jerusalem and Cytovia Therapeutics, Inc, a biopharmaceutical company engaged in the development of immunotherapies targeting Natural Killer (NK) cells, announced today a strategic collaboration in the development of precision medicines for both blood cancers and solid tumors. Under the collaboration, Cytovia will sponsor a research program for the development of multi-specific antibodies targeting both NK cells and the tumor antigen. The research will be led by Prof. Ofer Mandelboim from the Lautenberg Center for Immunology and Cancer Research at the Faculty of Medicine, Hebrew University.

Most current cancer immunotherapies target T-Cells, an extremely effective but sometimes toxic solution to the patient. Prof. Ofer Mandelboims research focuses on natural killer (NK) cells, an important part of the bodys immuno-surveillance system, with an ability to recognize and kill cancerous cells and viruses. Unlike T-cells, NK treatments offer the potential for an effective yet safer treatment option. Through his research, Prof. Mandelboims team has recently demonstrated that the NK activating receptor, NKp46, influences the FN1 expression by tumors, ultimately affecting its metastatic ability (Glasner et al. Immunity 2018).

Dr. Daniel Teper, Chairman and CEO of Cytovia said, We are delighted to collaborate with Professor Mandelboim, one of the foremost experts on natural killer (NK) cells, a first line of defense against cancer and viral infections. The NKp46 antibodies developed at the Hebrew University will be incorporated in our NK engager platform supporting the development of multiple novel therapeutic candidates for both hematological and solid tumors. This partnership positions Cytovia as an innovation leader in the rapidly growing field of NK engagers. We believe the potential for effective treatment is great.

Prof. Mandelboim commented: NKp46 is a major engager of NK cells including infiltrating cells in solid tumors. Pre-clinical studies have demonstrated that these multifunctional engagers have the potential for better tumor control without hurting the healthy cells. For patients and doctors alike, this precision medicine could become the optimal way to treat cancer.

About CYTOVIACytovia is dedicated to the development of transformational cancer immunotherapies, addressing several of the most challenging unmet medical needs including the prevention of cancer relapse and metastasis. Cytovia focuses on Natural Killer (NK) cell biology and applies precision medicine tools to develop the right therapy for the right patient at the right stage of the disease. Cytovia has secured access to multiple advanced technologies, including allogeneic cell therapy, multispecific antibodies, and cytokines. Cytovia establishes development partnerships to accelerate time-to-market and commercialization alliances in order to optimize rapid adoption of its novel immunotherapies. Learn more at http://www.cytoviatx.com

About Yissum Yissum is the technology transfer company of The Hebrew University of Jerusalem. Founded in 1964, it serves as a bridge between cutting-edge academic research and a global community of entrepreneurs, investors, and industry. Yissums mission is to benefit society by converting extraordinary innovations and transformational technologies into commercial solutions that address our most urgent global challenges. Yissum has registered over 10,750+ patents globally; licensed over 1050+ technologies and has spun out more than 170 companies. Yissums business partners span the globe and include companies such as Boston Scientific, Google, ICL, Intel, Johnson & Johnson, Merck, Microsoft, Novartis and many more. For further information please visit http://www.yissum.co.il

Media Contact: Estee Yaari, Media Relations, Yissum, Email: estee@yissum.co.il, Phone: +972 50 2007072

Contact information: CYTOVIA Therapeutics: Anna Baran-Djokovic VP, Corporate Affairs anna@cytoviatx.com Phone: +44 (0)7521083006 http://www.cytoviatx.com

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Hebrew University to Collaborate with Cytovia Therapeutics - GlobeNewswire

Cell Biology

Blocking Sugar Structures on Viruses and Cancer Cells – Technology Networks

During a viral infection, viruses enter the body and multiply in its cells. Viruses often specifically attach themselves to the sugar structures of the host cells, or present characteristic sugar structures on their surface themselves. Researchers at the Technical University of Munich (TUM) have developed a new type of protein reagent for identifying biological sugar structures, which may block the spread of an illness in the body if used for blocking the sugar structures of a cell or a pathogen.

The laboratory directed by Arne Skerra, Professor of Biological Chemistry, has its focus on designing artificial binding proteins for therapeutic applications. The laboratorys current research findings are paving the way for the development of new types of binding proteins for biological sugar structures, which play a significant role in cancer as well as infectious diseases.Recognizing biological sugar structuresThe recognition of specific sugar molecules, or so-called carbohydrates, is of vital importance in many biological processes, Prof. Skerra explains. Most cells carry a marker consisting of sugar chains which are attached to the outside of the cell membrane or to the membrane proteins, thus enabling the body to identify where these cells belong or whether certain cells are alien. Pathogens also have sugar structures of their own, or they can bind to these.

Proteins, which perform a wide range of functions within cells, generally have only low affinity to sugars. Thus, their molecular recognition poses a challenge. The reason: water molecules look similar to the sugar molecules, meaning that they are basically hidden in the aqueous environment of the cells. Prof. Skerras research group therefore set out to design an artificial binding protein with a peculiar chemical composition which makes it easier to bind to biological sugar structures.A boric acid group implemented into a protein as amino acidAmino acids are the building blocks of proteins. As a rule, nature only uses 20 amino acids in all living organisms. Using the possibilities opened up by synthetic biology, we have employed an additional artificial amino acid, reports researcher Carina A. Sommer.

We have succeeded in incorporating a boric acid group, which exerts intrinsic affinity to sugar molecules, into the amino acid chain of a protein. In doing this, we have created an entirely new class of binding protein for sugar molecules, Sommer explains. This artificial sugar-binding function is superior to natural binding proteins (so-called lectins) both in strength and with regard to possible sugar specificities.

The sugar-binding activity of boric acid and its derivatives has been known for nearly a century, says Prof. Skerra. The chemical element boron is common on earth and has low toxicity, but so far has largely remained unexplored by organisms.

By using X-ray crystallography, we have succeeded in unraveling the crystal structure of a model complex of this artificial protein, which allowed us to validate our biomolecular concept, explains scientist Dr. Andreas Eichinger.The next step: towards medical applicationFollowing approximately five years of fundamental scientific research, the findings from Prof. Skerras laboratory can now be applied to practical medical needs. Prof. Skerra points out: Our results should not only be used to support the future development of new carbohydrate ligands in biological chemistry, but should also pave the way for creating high-affinity agents for controlling or blocking medically-relevant sugar structures on cell surfaces.

Such a blocking agent could be used for conditions in which strong cell growth is evident or when pathogens are attaching themselves to cells, for example in oncology and virology. If we are successful in blocking the sugar-binding function and in slowing down the progress of a disease, this would give the patients immune system sufficient time to mobilize the body's natural defense.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Blocking Sugar Structures on Viruses and Cancer Cells - Technology Networks