Category Archives: Cell Biology

Cell Biology

Princeton Researchers Catalog the Gut Microbiomes Impact on Medications – SciTechDaily

Study investigates potential for the intestinal microbial community to alter drug safety and efficacy.

Researchers at Princeton University have developed a systematic approach for evaluating how the microbial community in our intestines can chemically transform, or metabolize, oral medications in ways that impact their safety and efficacy.

The new methodology provides a more complete picture of how gut bacteria metabolize drugs, and could aid the development of medications that are more effective, have fewer side effects, and are personalized to an individuals microbiome.

The study was published today (June 10, 2020) in the journal Cell.

Researchers at Princeton created a system for evaluating how the bodys gut bacteria alter the safety and efficacy of everyday drugs. The system can be used in pharmaceutical research to improve drug discovery and development. Credit: Janie Kim. Published in Cell

Previous studies have examined how single species of gut bacteria can metabolize oral medications. The new framework enables evaluation of a persons entire intestinal microbial community at once.

Basically, we do not run and hide from the complexity of the microbiome, but instead, we embrace it, said Mohamed S. Donia, assistant professor of molecular biology. This approach allows us to gain a holistic and more realistic view of the microbiomes contribution to drug metabolism.

The team used the approach to evaluate the gut microbiomes effect on hundreds of common medications already on the market. The intestines are the primary region where pills and liquid medications are absorbed into the body.

The researchers identified 57 cases in which gut bacteria can alter existing oral medications. Eighty percent of those had not been previously reported, emphasizing the potential of the method for revealing unknown drug-microbiome interactions.

These alterations range from converting the medicine into an inactive state which can reduce its efficacy to converting the drug into a form that is toxic, potentially causing side effects.

The framework could aid drug discovery by identifying potential drug-microbiome interactions early in development, informing formulation changes. The approach can also help during clinical trials to better analyze the toxicity and efficacy of drugs being tested.

The intestines are home to hundreds of species of bacteria. The makeup of these communities what kinds of bacteria and how many of each species can vary considerably from person to person.

This inter-person variability underscores why studying a single bacterial species makes it impossible to compare the microbiomes metabolism of drugs between individuals, Donia said. We need to study the entire intestinal microbial community.

The researchers found that some peoples microbiomes had little effect on a given drug, while other microbiomes had a significant effect, demonstrating how important the community of bacteria rather than just single species is on drug metabolism.

Everyones microbiome is unique, and we were able to see this in our study, said Bahar Javdan, an M.D.-Ph.D. student in molecular biology and a co-first author on the study. We observed three main categories drugs that were consistently metabolized by all the microbiomes in our study, drugs that were metabolized by some and not by others, and drugs that were not subject to any microbiome-derived metabolism.

The methodological approach could be valuable for personalizing treatment to the microbiome of each patient. For example, the framework could help predict how a certain drug will behave, and suggest changes to the therapeutic strategy if undesired effects are predicted.

This is a case where medicine and ecology collide, said Jaime Lopez, a graduate student in the Lewis-Sigler Institute for Integrative Genomics and a co-first author on the study, who contributed the computational and quantitative analysis of the data. The bacteria in these microbial communities help each other survive, and they influence each others enzymatic profiles. This is something you would never capture if you didnt study it in a community.

The framework involves four steps for systematically evaluating the intestinal microbiomes effect on drugs.

First, the researchers collected 21 fecal samples collected from anonymous donors and cataloged the bacterial species living in each individual. They found that the donors each had a unique microbial community living in their guts, and that the majority of these personalized communities can be grown in a lab culturing system that they developed.

Next, they tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported, as well as ones that have been reported in humans and associated with side effects but their origins were unknown. They found cases where all the donor microbiomes performed the same reactions on the drug, and others where only a subset did.

Then they examined the mechanisms by which some of the modified drugs are altered by the cultured microbiomes. To understand exactly how the transformations occurred, they traced the source of the chemical transformations to particular bacterial species and to particular genes within those bacteria. They also showed that the microbiome-derived metabolism reactions that are discovered in this manner can be recapitulated in a mouse model, the first step in adapting the approach for human drug development.

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Reference: Personalized mapping of drug metabolism by the human gut microbiome by Bahar Javdan, Jaime G. Lopez, Pranatchareeya Chankhamjon, Ying-Chiang J.Lee, Raphaella Hull, Qihao Wu, Xiaojuan Wang, Seema Chatterjee and Mohamed S. Donia, 10 June 10, 2020, Cell.DOI: 10.1016/j.cell.2020.05.001

Additional contributors to the study were postdoctoral research associates Pranatchareeya Chankhamjon, Qihao Wu and Xiaojuan Wang; graduate student in molecular biology Ying-Chiang J. Lee, graduate student at Cambridge University Raphaella Hull; and Seema Chatterjee, research lab manager.

Funding for this study was provided by the Princeton Department of Molecular Biology, the National Institutes of Health, the New Jersey Commission on Cancer and the National Science Foundation.

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Princeton Researchers Catalog the Gut Microbiomes Impact on Medications - SciTechDaily

Cell Biology

Coming of age in 2020 the summer without exams or school proms – Metro Newspaper UK

Isabelle Catherine Winder, lecturer in zoology; Gwyndaf Roberts, lecturer in cell biology; Vivien Shaw, lecturer in anatomy all of Bangor University

THE transition from childhood to adulthood is marked by humans in a wide variety of ways across the world. Many of these coming of age celebrations are held at puberty. For instance, the filing of front teeth in Bali is said to ease the sad ripu or six evils of lust, greed, wrath, pride, jealousy and intoxication. In contrast, the Jewish bar mitzvah marks the point at which children are deemed to be responsible for their own actions.

Demonstrations of physical prowess are often tied to male ceremonies. The start of periods may play the same role for girls, with rituals such as the Apache sunrise ceremony marking the passage into womanhood.

Despite the differences in the style of all these events, they often have three elements in common: they are public, and involve special clothes and particular foods. This places these rituals squarely into the cultural realm, which may explain the wide variation. Culture is especially variable, as it is passed on socially and often serves to mark inclusion into a particular group.

Some of our close relatives also have culture. Chimpanzee groups, for instance, have specific grooming postures, make different signals to one another, and use tools in specific ways. Yet they do not have clear rites of passage. These seem to be a particularly human phenomenon. They serve to strengthen bonds between society members, and create cohesion in the broader social group.

In the multicultural society of England and Wales, one significant rite of passage familiar to almost all of us is the nationwide ritual of the summer exam. For year 11 and year 13 pupils in particular, the completion of GCSEs and A-levels marks a point of shared experience, effort and decision making.

For many years now, this momentous achievement has been widely celebrated with a school prom. This American import frequently demands the formation of the prom committee, and an almost military level of planning. The venue, theme, entertainment and decoration are all organised and debated to the finest detail.

There is also often significant financial and emotional investment ahead of an event at which social competition is intense, and full of almost ritualistic preparation (hair, make-up, maybe a spray tan).

For the class of 2020, these important landmarks of exams and proms have been lost to coronavirus. Instead, results will be estimated, and social gathering will be extremely limited.

Young people also face unprecedented uncertainty about what happens next. Should they stick to their original plans, or put them on hold?

Whatever they decide, it is important to remember that one of the main functions of these kinds of rituals is to welcome the child into the adult world. They allow them for the first time to engage not just with their peers, but also with adults as equals.

So while it might seem depressing that exams and proms have been cancelled this year, recognising these celebrations as specifically cultural and symbolic can help. By encouraging young people to think about how they might like to mark their graduation, we can make a good start.

If they cant do it by moving to a new city to start university, is there some other way to mark it? One suggestion could be a significant personal challenge such as a long hike or cycle ride. In the absence of a prom, is there a different kind of celebration perhaps a Zoom party that could be held and shared through social media?

Different friendship groups have their own ways of interacting, and may thrive on creating something innovative and new for themselves. Parents can help by recognising the significance of this life stage.

In a sense, the class of 2020 have a unique opportunity to take a truly independent approach to marking this transition, and deciding on its level of importance. Everything is open for discussion and there is much less pressure to do things as they have always been done.

The situation allows them to reinvent coming of age in a way that is personally meaningful. Young people can take control over their own transition and decide how, in the post-coronavirus years, they take their lives forward.

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Coming of age in 2020 the summer without exams or school proms - Metro Newspaper UK

Cell Biology

Magenta Therapeutics to Participate in Upcoming Healthcare Investor Conferences – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that the company will participate in a fireside chat and hold investor meetings at the 41st annual Goldman Sachs Healthcare Conference on June 11th, 2020. The Company will also hold investor meetings and participate in a panel discussion on novel approaches for gene therapy on Monday, June 15th at the Raymond James Human Health Innovation Conference.

A live webcast of the fireside chat at the Goldman Sachs conference can be accessed on the Magenta Therapeutics website at https://investor.magentatx.com/events-and-presentations. The webcast replay will be available for 90 days following the event.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics to Participate in Upcoming Healthcare Investor Conferences - Business Wire

Cell Biology

Cells inside Cells: The Bacteria That Live in Cancer Cells – India Education Diary

New Delhi: Cancer cells are comfy havens for bacteria. That conclusion arises from a rigorous study of over 1,000 tumor samples of different human cancers. The study, headed by researchers at the Weizmann Institute of Science, found bacteria living inside the cells of all the cancer types from brain to bone to breast cancer and even identified unique populations of bacteria residing in each type of cancer. The research suggests that understanding the relationship between a cancer cell and its mini-microbiome may help predict the potential effectiveness of certain treatments or may point, in the future, to ways of manipulating those bacteria to enhance the actions of anticancer treatments. The findings of this study were published in Science.

Dr. RavidStraussman of the Institutes Molecular Cell Biology Department had, several years ago, discovered bacteria lurking within human pancreatic tumor cells; these bacteria were shown to protect cancer cells from chemotherapy drugs by digesting and inactivating these drugs. When other studies also found bacteria in tumor cells, Straussman and his team wondered whether such hosting might be the rule, rather than the exception. To find out, Drs. Deborah Nejman and Ilana Livyatan in Straussmans group and Dr. GaroldFuks of the Physics of Complex Systems Department worked together with a team of oncologists and researchers around the world. The work was also led by Dr. Noam Shental of the Mathematics and Computer Science Department of the Open University of Israel.

Ultimately, the team would produce a detailed study describing, in high resolution, the bacteria living in these cancers brain, bone, breast, lung, ovary, pancreas, colorectal and melanoma. They discovered that every single cancer type, from brain to bone, harbored bacteria and that different cancer types harbor different bacteria species. It was the breast cancers, however, that had the largest number and diversity of bacteria. The team demonstrated that many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors, and that some bacteria were preferentially found in the tumor tissue rather than in the normal tissue surrounding it.

To arrive at these results, the team had to overcome several challenges. For one, the mass of bacteria in a tumor sample is relatively small, and the researchers had to find ways to focus on these tiny cells-within-cells. They also had to eliminate any possible outside contamination. To this end they used hundreds of negative controls and created a series of computational filters to remove the traces of any bacteria that could have come from outside the tumor samples.

The team was able to grow bacteria directly from human breast tumors, and their results proved that the bacteria found in these tumors are alive. Electron microscopy visualization of these bacteria demonstrated that they prefer to nestle up in a specific location inside the cancer cells close to the cell nucleus.

The team also reported that bacteria can be found not only in cancer cells, but also in immune cells that reside inside tumors. Some of these bacteria could be enhancing the anticancer immune response, while others could be suppressing it a finding that may be especially relevant to understanding the effectiveness of certain immunotherapies, says Straussman. Indeed, when the team compared the bacteria from groups of melanoma samples, they found that different bacteria were enriched in those melanoma tumors that responded to immunotherapy as compared to those that had a poor response.

Straussman thinks that the study can also begin to explain why some bacteria like cancer cells and why each cancer has its own typical microbiome: The differences apparently come down to the choice of amenities offered in each kind of tumor-cell environment. That is, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. For example, when the team compared the bacteria found in lung tumors from smokers with those from patients who had never smoked, they found variances. These differences stood out more clearly when the researchers compared the genes of these two groups of bacteria: Those from the smokers lung cancer cells had many more genes for metabolizing nicotine, toluene, phenol and other chemicals that are found in cigarette smoke.

In addition to showing that some of the most common cancers shelter unique populations of bacteria within their cells, the researchers believe that the methods they have developed to identify signature microbiomes with each cancer type can now be used to answer some crucial questions about the roles these bacteria play: Are the bacteria freeloaders on the cancer cells surplus metabolites, or do they provide a service to the cell? At what stage do they take up residence? How do they promote or hinder the cancers growth? What are the effects that they have on response to a wide variety of anticancer treatments?

Tumors are complex ecosystems that are known to contain, in addition to cancer cells, immune cells, stromal cells, blood vessels, nerves, and many more components, all part of what we refer to as the tumor microenvironment. Our studies, as well as studies by other labs, clearly demonstrate that bacteria are also an integral part of the tumor microenvironment. We hope that by finding out how exactly they fit into the general tumor ecology, we can figure out novel ways of treating cancer, Straussman says.

Dr. RavidStraussmans research is supported by the Roel C. Buck Career Development Chair; the Moross Integrated Cancer Center; the Maurice and Vivienne Wohl Biology Endowment; the Fabricant-Morse Families Research Fund for Humanity; the Chantal Dadesky-Scheinberg Research Fund; the Rising Tide Foundation; and the European Research Council.

The Weizmann Institute of Science in Rehovot, Israel, is one of the worlds top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

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Cells inside Cells: The Bacteria That Live in Cancer Cells - India Education Diary

Cell Biology

Forma Therapeutics Announces Phase I Clinical Data for Investigational Agent FT-4202 in Sickle Cell Disease to be Presented at the Virtual Edition of…

Poster presentation to highlight the tolerability, pharmacokinetics and pharmacodynamics of FT-4202 in Phase I clinical trials of single and multiple ascending dose cohorts of healthy subjects, Phase I clinical trials of single dose of SCD patients

WATERTOWN, Mass.--(BUSINESS WIRE)-- FORMA Therapeutics, Inc.. (Forma), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced that the company will present Phase 1 results from a study of FT-4202, Formas lead investigational agent currently in clinical development as a potentially disease-modifying treatment for sickle cell disease (SCD), at the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress taking place June 11-21, 2020.

The abstract, listed below, is currently available on the EHA website.

Poster Presentation Title: Phase 1 Single (SAD) and Multiple Ascending Dose (MAD) Study of the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of FT-4202, a PKR Activator, in Healthy and Sickle Cell Disease Subjects Abstract Number: EP1531Date and Time: Available on EHAs website beginning June 12, 2020, at 8:30 a.m. Central European Summer Time (CEST)Session Topic: Sickle Cell DiseasePresenter: Jeremie H. Estepp, M.D., St. Jude Childrens Research Hospital

The abstract and poster presentation will be available on Formas website upon presentation at the meeting. In addition, the e-Poster will be made available on the on-demand Virtual Congress platform as of Friday, June 12, at 8:30 CEST and will be accessible until October 15, 2020.

About FT-4202

FT-4202 is a novel, oral, once-daily pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD). Early studies and trials have shown that FT-4202 works upstream by employing a multimodal approach and activating the red blood cells (RBC) natural PKR activity to decrease 2,3-DPG levels, which we believe leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. FT-4202 has also shown downstream activity by increasing ATP levels, the fuel that provides energy to cells, which we believe may improve RBC health and survival. Together, these effects have the potential to increase hemoglobin levels and decrease painful vaso-occlusive crises. In preclinical safety studies, FT-4202 did not inhibit aromatase activity, important biological processes responsible for sexual development.

About Forma Therapeutics

Forma Therapeutics is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to transform the lives of patients with rare hematologic diseases and cancers. Our R&D engine combines deep biology insight, chemistry expertise and clinical development capabilities to create drug candidates with differentiated mechanisms of action focused on indications with high unmet need. Our work has generated a broad proprietary portfolio of programs with the potential to provide profound patient benefit. For more information, please visit http://www.FormaTherapeutics.com or follow us on Twitter @FORMAInc and LinkedIn.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200609005144/en/

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Forma Therapeutics Announces Phase I Clinical Data for Investigational Agent FT-4202 in Sickle Cell Disease to be Presented at the Virtual Edition of...

Cell Biology

Covid-19: What’s the most infectious place in school? – TES News

After the screaming headlines and point-scoring in the political battle over the full reopening of schools, theres a quiet, serious new reality for teachers and teaching assistants: spending every day in a workplace where they may be worried or scared about the risks of infection.

Plenty of teachers will be turning over questions throughout the day: is that trip beyond your bubble to the loo a bit dicey? Could the novel coronavirus be lurking in a pupils well-thumbed Dickens novel?

Read more

The science of school closures:An overview for schools

Should teachers wear face masks?A professor of public health gives her view

Coronavirus:Can childrensocially distance?

One of the big unknowns about the coronavirus, where research is yet to reach a consensus, is whether children have a significant role in transmission or a minimal one. But scientists do agree on other aspects of how the virus is transmitted, shedding light on which areas of a school might present the highest risks and on how schools might mitigate those risks.

When we speak, cough, sneeze and breath, we produce droplets that are of respirable/inhalable size, small droplets known as aerosol, and also much larger dropletsthat are even larger than the diameter of a human hair, explains Jonathan Reid, professor of physical chemistry at the University of Bristol and an expert on aerosols.

The larger droplets fall quickly to the ground in a few seconds and could contaminate surfaces, offering an indirect, but important way viruses are transmitted, he adds.

Then theres the risk of being directly exposed to larger droplets when someone sneezes or coughs if they are standing nearby, hence physical distancing guidance.

But theres also a question over whether infection can take place via those small aerosol particles, which can remain suspended in the air for many minutes or even hours. Given the difficulties in persuading primary school children, in particular, to distance from each other or from staff perhaps more like impossibilities the question could be a pressing one for schools.

One study, led by researchers from the US National Institute of Allergy and Infectious Diseases and published in a brief summary in the New England Journal of Medicine, says its results suggest that novel coronavirus transmission via aerosol and surfaces is plausible. Researchersfound that the virus can remain viable and infectious in aerosols for hours and on surfaces up to days.

However, that research took place in lab rather than real-life conditions; plenty of scientists think that the evidence on aerosol transmission is inconclusive at present. Reid is attempting to offer more definitive answers in a study.

Which areas of a school does Reid think might present the highest risk of infection? I would say anywhere that is unventilated or poorly ventilated, has a high throughput of people or where there can be contaminated surfaces or poor hygiene so, for example, toilets, he replies.

Lawrence Young, a virologist and a professor of molecular oncology at the University of Warwick, agrees: Any indoor environment where there is poor ventilation is a risk for transmission. This would be exacerbated by having many individuals walking through an area like a corridor or communal area. Social distancing in these areas is essential.

Peter Collignon, an infectious diseases physician and microbiologist at Canberra Hospital and a professor at the Australian National University, says that in a school the key means of potential virus transmission are teachers and parents, making staffrooms and indoor meetings with parents the riskiest areas.

He suggests limiting staffroom numbers to allow for social distancing and trying to be outdoors more than indoors in general.

Many schools are utilising outdoor spaces whenever they can. But rainy spells and winter will bring the need to manage increased use of corridors and communal areas.

When it comes to viruses survival on surfaces, one authority is Bill Keevil, professor of environmental healthcare at the University of Southampton. His research has found that the coronavirus that causes the common cold, which he describes as structurally almost identical to the new virus, survived at least five days on stainless steel, glass, plastics, ceramics.

Similarly, the New England Journal of Medicine study found the novel coronavirus was detected on plastic after 72 hours but could not be found on cardboard after 24 hours.

So perhaps plastic desktops should be a focus for cleaning, with book covers less of a concern for long-lasting infection risk.

Should school staff be worried if they touch a door handle and forget to wash their hands afterwards?

I would be, because Im a microbiologist, Professor Keevil replies, none too reassuringly. Humans, were very tactile. We continually touch our faces, eyes, nose and mouth anything from 15 to 30 times an hour.

The highest-risk surfaces would be the obvious touch ones, he adds: door handles and push plates, stair rails and toilet areas, particularly for younger children.

However, other researchers point to reasons not to cower in fear before every surface.

Dont panic, says Collignon of the risks of touching a door handle. Being close to someone inside with a cough for over 15 minutes is very much higher risk. But use hand sanitisers before touching your face or eating.

In response to the 72-hour figure for the virus survival on plastic found by the New England Journal of Medicine study, Johns Hopkins University professor of cell biology Carolyn Machamer has noted that just 0.1 per cent of the virus material remains after that time, making infection unlikely.

She has told the Johns Hopkins website that people 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.

And perhaps there is another solution for schools on surfaces. Keevil has been studying the antimicrobial effects of copper for 20 years, with his research on other coronaviruses finding that they were inactivated in minutes when they came into contact with such surfaces.

If you enjoy the idea of the coronavirus taking a beating, then savour Keevils description of how macho-sounding copper ions can punch holes in the cell membrane of a bacterium or virus, allowing the ions to flood into the cell, inhibit the respiration of bacteria then destroy DNA and RNA in both bacteria and viruses, which means there is no chance of mutation and resistance.

He highlights a Greek study that found reduced rates of respiratory infections in schools where copper alloys were used to cover or replace surfaces such as stair rails.

Surfaces can be coated in copper, Keevil says, so rather than have to completely rekit schools in solid copper alloysas an interim, you can go in and cover them.

Aside from such potential innovations, the best options for schools at present seem to lie in ventilation, physical distancing (or attempts at it)and, of course, routine and frequent cleaning.

But theres plenty above for school staff to consider while weighing up a trip to the socially distanced staffroom. Just make sure you dont touch your face while youre thinking about it.

John Morgan is a freelance journalist

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Covid-19: What's the most infectious place in school? - TES News

Cell Biology

IIT-M researchers show role of microRNA in growth and spread of tongue cancer cells – The Hindu

Researchers at the Indian Institute of Technology Madras have identified a specific microRNA (miRNAs) called miR-155 that is over-expressed in tongue cancer. The research team has shown that knocking out miR-155 causes death of cancer cells, arrests the cell cycle and regresses tumour size in animal models and reduces cell viability and colony formation in bench top assays.

The finding could help develop molecular strategies to manipulate miR-155 expression to develop therapeutics for tongue cancer.

The miRNAs affect cancer growth through inhibiting or enhancing the functions of certain proteins.

The research team of Devarajan Karunagaran, head of the Biotechnology department and his research scholar Shabir Zargar, collaborated with researchers from the Adyar Cancer Institute and the Sree Balaji Dental College and Hospital in the city and the Indian Institute of Science, Bengaluru.

Their research paper was published in the journal Molecular and Cellular Biology.

Mr. Karunagaran said: MicroRNAs (miRNAs) are short noncoding RNAs containing 2024 nucleotides that participate in virtually all biological pathways in animals. They have been found to play important roles in many cancers, in carcinogenesis (start of cancer), malignant transformation and metastasis the development of secondary cancer. The miRNAs associated with cancer are called Oncomirs.

Many of the Oncomirs affect cancer by suppressing the performance of tumour-suppressing agents. Some of them can prevent the growth and spread of cancer cells and yet others prevent tumour growth itself, he said.

miRNA manipulation is being combined with conventional cancer treatment methods such as chemotherapy, radiotherapy and immunotherapy.

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IIT-M researchers show role of microRNA in growth and spread of tongue cancer cells - The Hindu

Cell Biology

Preventing pancreatic cancer metastasis by keeping cells sheltered in place – Newswise

Newswise Scientists atSanford Burnham Prebys Medical Discovery Institutehave shown that pancreatic cancer metastasiswhen tumor cells gain the deadly ability to migrate to new parts of the bodycan be suppressed by inhibiting a protein called Slug that regulates cell movement. The study, published in theJournal of Experimental Medicine, also revealed two druggable targets that interact with Slug and hold promise as treatments that may stop the spread of pancreatic cancer.

Pancreatic cancer cells are notorious for their ability to escape from a tumor. Even when pancreatic cancer is caught early, tumor cells are already found circulating throughout the body, saysCosimo Commisso, Ph.D., an associate professor in Sanford BurnhamPrebysNCI-designated Cancer Centerand senior study author. Our study suggests that we may be able to create treatments that stop pancreatic cancer cells from untethering in the first place, which could reduce metastasis and help more people survive this deadly cancer.

Stopping the migration of hungry cancer cells

Pancreatic cancer cells, like all cancer cells, grow rapidly and quickly deplete the nutrients in their surrounding environment. To meet their energy needs, tumor cells boost metabolic pathways that normal cells dont use.Commissois working to understand how pancreatic cancer cells respond to nutrient deprivationfocusing on themost commonly depletednutrient, glutaminewith the goal of finding treatments that stop the growth of cancer cells without harming healthy cells.

In the study, the scientists used a mouse model of pancreatic cancer to show that, in response to glutamine deficiency, a protein called Slug drives metastasis by activating the epithelial-mesenchymal transition, or EMTthe process cells use to free themselves from tightly packed tissue. Inhibiting Slug reduced the cancers ability to spreaddemonstrated by a reduction in the number and size of secondary lung tumors. The scientists also established that patient samples with higher levels of Slug were linked to a poor prognosisfurther indicating that blocking the protein may be beneficial.

The field of pancreatic cancer research is still working to understand the role of EMT in metastasis. Our study shows that glutamine deficiency indeed activates EMT, through Slug, to allow pancreatic cancer cells to escape and look for nutrient-rich grounds, says Maria VictoriaRecouvreux, Ph.D., a staff scientist in theCommissolab at Sanford BurnhamPrebysand the first author of the study. In addition to revealing new therapeutic avenues that may halt pancreatic cancer metastasis, these findings might also apply to other tumors that rapidly consume glutamine, including lung and colon cancers.

Because Slug is considered undruggable due to inherent biological properties, the scientists continued to search for proteins that interact with Slug and could be targeted with a drug. Their research identified two promising targets: ERK and eIF2 alpha. ERK inhibitors are currently under evaluation in clinical trials for pancreatic and other cancers; and an eIF2 alpha inhibitor has completed animal testing.

New hope for a deadly cancer

Once pancreatic cancer metastasizes, the number of people who are alive five years later drops from 37% to only 3%. Of the57,000 Americansexpected to be diagnosed with pancreatic cancer in 2020, about10% are diagnosed at an early stageand may benefit from a drug that prevents metastasis. For unknown reasons, pancreatic cancer is on the rise and predicted to become the second-leading cause of cancer-related deaths in the U.S.

Now that the researchers have established the important role of Slug in driving metastatic pancreatic cancer, they plan to expand their research to determine Slugs role in pancreatic cancer overall, including impact on disease aggressiveness and survival.

To make progress in the fight against pancreatic cancer, it is critical that we have a strong scientific understanding of what is driving the tumors growth and metastasis, says LynnMatrisian, Ph.D., chief science officer at thePancreatic Cancer Action Network(PanCAN), who wasnt involved in the study. Todays findings reveal new insights into how pancreatic cancer metastasizes, providing both hope and important new directions for research that might be able to help more people survive the worlds toughest cancer.

The studys DOI is 10.1084/jem.20200388.

Research reported in this press release was supported by the National Institutes of Health (NIH) (R01CA207189 and P30CA030199).

Additional study authors include Matthew Moldenhauer, Koen M.O.Galenkamp, Michael Jung, Brian James,YijuanZhang and AnindyaBagchiof Sanford BurnhamPrebys; and Andrew Lowy of UC San Diego.

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About Sanford BurnhamPrebysMedical Research Institute

Sanford BurnhamPrebysis a preeminent, independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 40 years, our research has produced breakthroughs in cancer, neuroscience, immunology and childrens diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities. For more information, visit us atSBPdiscovery.orgor on Facebook atfacebook.com/SBPdiscoveryand on Twitter@SBPdiscovery.

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Cell Biology

Add ear gene therapy company Akouos to the ever-growing list of IPOs amid Covid-19 – Endpoints News

For investors looking to cash in on a burgeoning ear therapy space, the latest biotech angling for a public debut could be music to their ears.

Fresh off a $105 million raise in March, ear gene therapy company Akouos is looking for another $100 million for a chance to dance on the Nasdaq well before its lead product enters the clinic.

Hearing aids and cochlear implants do address ear damage caused by genetics, noise, aging, or drugs, but nothing quite cures or indeed targets the biological underpinnings of hearing loss this is the gap Akouos and a handful of others in the space want to bridge.

I think some of the early efforts in the hearing space have been drawn to the largest affected populations where there happens to be less clarity on the underlying biology mechanism, chief Manny Simons said in a previous interview with Endpoints News. So were focusing our attention on forms of hearing loss that we feel are well-understood, well-characterized, where we can potentially address the underlying cause.

The companys lead experimental therapy AK-OTOF is engineered to treat hearing loss due to mutations in the gene that encodes otoferlin, a protein that enables the sensory cells to activate auditory neurons that carry electronically encoded acoustic information to the brain, which allows us to hear.Akouos plans to submit an application to take the drug into human studies next year, and generate early-stage data in 2022.

Simons, who founded the company in 2016, initially flirted with the idea of becoming a musician, growing up playing the piano and the trumpet. He met his wife at a glee club at Harvard. For his bachelors degree, he had the opportunity to essentially create his own course of study: to understand how the brain processes music, on the basis of imaging studies. That path led to the ear to decipher how sound is encoded into a neural impulse that can extend deep into the brain.

After getting his first taste of entrepreneurship in the prolific lab of drug delivery researcher Bob Langer, he got his biopharma training wheels off with stints at Third Rock backed-Warp Drive Bio and Voyager Therapeutics (neither of which were ear focused). But when he learned that AAV vectors with potential applications for the ear were being developed in a laboratory at Massachusetts Eye and Ear, Simons seized the opportunity to get a hearing-focused gene therapy company off the ground.

After securing a sweet $7.5 million in seed funding in 2018, Akouos scored $50 million in a Series A round in 2018, led by 5AM and New Enterprise Associates.

Akouos, akin to some others in the gene and cell therapy space, is investing heavily in manufacturing infrastructure having taken note that the complex manufacturing process for these kinds of therapies has become something of an Achilles heel in the field when it comes to adoption if the production apparatus is not up to scratch. For instance, the uptake of CAR-T therapies Novartis Kymriah and Gileads Yescarta underwhelmed initial expectations, despite their abundant promise. The uptake of Kymriah was plagued by manufacturing problems, and despite Novartis attempt to expand its capacity, sales have disappointed commercially, giving Yescarta an edge in the market.

Akouos is building its own infrastructure to manufacture vectors for its slate of experimental therapies, which also include genetic medicines for the most common forms of hearing loss, such as age-related and noise-induced hearing loss. The company is also planning on building a plant to process gene therapy batches to support activities through Phase I/II clinical trials for product candidates beyond AK-OTOF partner Lonza will help manufacture AK-OTOF while it is shepherded through clinical development.

The company plans to list on the Nasdaq under the symbol AKUS amid a broader rush of biopharma companies that are making their way to the public markets despite the disruption of Covid-19. Indeed, investor appetites have appeared seemingly insatiable given the raft of splashy IPOs in recent weeks, including a $424 million debut for a J&J-partnered Chinese biotech Legend Biotech, marking one of the largest public raises in biotech history.

Meanwhile, there are a host of rivals in the broader ear-focused space. Also in Boston, Akouos home, is Decibel Therapeutics, working on regeneration by targeting tiny hairs that grow in the inner ear to address congenital hearing loss or age-related balance disorders. Frequency Therapeutics has a mid-stage hair cell regeneration program using progenitor cells.

Across the Atlantic, UK-based Rinri Therapeutics is working on treating hearing loss by transplanting otic neural progenitor cells into the inner ear. Amsterdam-based Audion Therapeutics has a compound in-licensed from Eli Lilly, which is designed toturn on a chemical switch to produce new sensory hair cells from other cells in the inner ear to improve hearing.

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Add ear gene therapy company Akouos to the ever-growing list of IPOs amid Covid-19 - Endpoints News

Cell Biology

Ability to ‘Create’ Astrocytes Supports Their Damaging Role in MS… – Multiple Sclerosis News Today

An inflammatory environment can turn astrocytes, key supportive cells for neurons, into their killers, fostering the progression of neurodegenerative diseases like multiple sclerosis (MS), a new study shows.

This work, led by researchers at the New York Stem Cell Foundation(NYSCF), created for a first time astrocytes derived from human induced pluripotent stem cells (hIPSCs). The group then placed these cells in an inflammatory environment, and observed what happened.

Now that we can create this critical brain cell type from any individuals stem cells and capture its errant behaviors, we can better understand its role in diseases like multiple sclerosis, Parkinsons, and Alzheimers, Susan L. Solomon, the CEO of theNYSCF, said in a press release.

This will shed new light on the devastating process of neurodegeneration, pointing us towards effective treatments for this growing group of patients, Solomon added.

The study CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes was published in the journal Neuron.

Astrocytes compose more than half of the cells of the central nervous system (brain and spinal cord), and work as support cells. They help to maintain brain homeostasis (stable equilibrium), provide neurons with metabolic support, enhance the connectivity of neural circuits, and control the brains blood flow.

Yet, these cells are also thought to be key players in the onset and progression of neurodegenerative diseases such as MS.

Knowledge on astrocyte biology has mostly come from animal models, namely rodents, since scientists struggle to obtain astrocytes from people.

NYSCF researchers developed a method to generate functional astrocytes that are derived from human IPSCs. (IPSCs themselves arederived from either skin or blood cells that have been reprogrammed back into a stem cell-like state, which allows for the development of an unlimited source of almost any type of human cell.)

They based their work on a previous protocol, which they developed to produce oligodendrocytes one type of cell capable of producing myelin, the protective layer covering nerve fibers and whose loss triggers MS.

Here, the researchers generated a mix of astrocytes and neurons.

They then conducted a screen to identify a surface protein that could be used to specifically purify astrocytes.

The marker CD49f was found to distinguish astrocytes from neuronal progenitors and neurons. At the genetic level, cells isolated using this marker showed activity of genes characteristic of both mature and immature astrocytes. However, when researchers looked at individual cells, they saw that CD49f was more enriched in mature astrocytes.

The hIPSCs-derived astrocytes expressing CD49f helped in neuronal growth, neural communication, provided metabolism support including glutamate uptake, and secreted molecules (called cytokines) in response to inflammation triggers.

We were excited to see that our stem-cell-derived astrocytes isolated with CD49f behaved the way typical astrocytes do: they take up glutamate, respond to inflammation, engage in phagocytosis which is like cell eating and encourage mature firing patterns and connections in neurons, said Valentina Fossati, PhD,the studys lead author.

CD49f expression was found to be specific for astrocytes in samples from both healthy and diseased human brains.

We looked at human brain tissue samples from both a healthy donor and a patient with Alzheimers disease and found that these astrocytes also expressed CD49f suggesting that this protein is a reliable indicator of astrocyte identity in both health and disease, Fossati added.

Researchers next focused on addressing the question of how astrocytes misbehave in disease.

They stimulated hIPSCs-derived cells with interleukin (IL)-1b and TNF-a, two molecules known to trigger the transition of astrocytes into a neurotoxic state (called A1 reactive astrocytes) in animal models. Cells reacted by secreting pro-inflammatory cytokines, including IL-6, IL-1 alpha, and ICAM-1.

Theseastrocytes lost their capacity to uptake (absorb) glutamate, a metabolite that is toxic to neurons. They also changed their morphology, becoming constricted instead of spreading out with long arms.

To assess whether reactive A1 astrocytes would damage neurons, the team grew neurons with stimulated and unstimulated astrocytes, or treated neurons with molecules produced by astrocytes.

Astrocytes in a reactive state were seen to decrease the electric activity of neurons and to increase their apoptosis a programmed process of cell death thats a form of suicide.

These findingsdemonstrate the specific neurotoxicity of A1 hiPSC-derivedastrocytes, the researchers wrote.

They also confirmprevious work in mice, where researchers observed that inflammation turns astrocytes neurotoxic. This work was led by Shane Liddelow, PhD, an assistant professor at the NYU Grossman School of Medicine and an author of the current study.

We observed in mice that astrocytes in inflammatory environments take on a reactive state, actually attacking neurons rather than supporting them, Liddelow said.

The latest work, the researchers concluded, showed that CD49f is a reactivity-independent,astrocyte-specific cell surface antigen that is present at allstages of astrocyte development in hiPSC-derived cultures.

Astrocytes isolated with this marker recapitulatein vitrocriticalphysiological functions, they continued, and following inflammatory stimulationbecome reactive, dysfunctional, and toxic, triggering neuronaldeath all of which opens a window for the study of their role in neurodegenerative disorders.

What we saw in the dish confirmed what Dr. Liddelow saw in mice: the neurons began to die, Fossati said. Observing this rogue astrocyte phenomenon in a human model of disease suggests that it could be happening in actual patients.

She and the others now look forward to using our new system to further explore the intricacies of astrocyte function in Alzheimers, multiple sclerosis, Parkinsons, and other diseases, in the hope it will point us toward new treatment opportunities that might slowor prevent neurodegeneration.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

Read more from the original source:
Ability to 'Create' Astrocytes Supports Their Damaging Role in MS... - Multiple Sclerosis News Today