Category Archives: Cell Biology

A study published in Nature last week explains why certain kinds of cancer cells often spread to the lymph nodes before various organs within the body. Researchers from the Childrens Medical Center Research Institute at UT Southwestern (CRI) have discovered melanoma cells that pass through the lymph nodes and pick up a protective coating. This allows them to survive oxidative stress within the blood, and travel to organs further in the body, where they eventually become tumors.

"Previous research has focused on how cancer cells metastasize through the blood, but very little was known about how these cells compare to cells that metastasize through lymphatics," said Sean Morrison, Ph.D., the director of CRI and a Howard Hughes Medical Institute investigator. "Our data suggest that passing through the lymphatics can promote the survival and spread of melanoma cells by protecting the cells from the oxidative stress they normally experience during metastasis."

Using mice, the researchers looked at how melanoma cells acted when injected intravenously or into the lymphatic system. They discovered that cancer cells that were injected into the lymph nodes had a higher chance of survival, compared to those that were injected directly into the blood.

The researchers believe that this difference can be explained by the high levels of oxidative stress cancer cells go through when they move through the blood.

"After further analysis, we discovered that the oxidative stress in the blood causes the cancer cells to undergo a specific form of cell death called ferroptosis," said Jessalyn Ubellacker, Ph.D., lead author of the study and a postdoctoral researcher in the Morrison lab. "In contrast, cancer cells in lymph experience lower levels of oxidative stress and are protected from ferroptosis."

The lymphatic system is specifically designed to protect the body against foreign invaders. However, experts know little about how the activation of immune cells in the lymph nodes can occur without damaging the lymphatic system. This week, an article published in Nature Communications shed light on research conducted by experts at the Moffitt Cancer Center that may finally provide some answers.

"Acidosis is a potent inhibitor of effector T cell functions," said Robert Gillies, Ph.D., chair of the Department of Cancer Physiology at Moffitt. "Oxygen levels are reported to be low in lymph nodes and that hypoxic tissue is acidic. We wanted to determine if lymph nodes were also acidic."

The researchers believe that there is a novel acidic niche within lymph nodes that plays a critical role in regulating T cell activation. They used fluorescence and magnetic resonance imaging to discover that T cells were the source of acidity. These results ultimately pointed to localized acidosis as a key component of the adaptive immune response.

The findings by the researchers also demonstrated the potential role for the lymph node microenvironment in shaping T cell biology. T cells that are activated by antigen-presenting cells produce an acidic environment, which is balanced by the capacity to generate lactic acid.

"The low extracellular pH of lymph nodes does not impair the T cell's activation, but it does suppress the cytokine production, which is likely what protects lymph nodes from being attacked by the immune system," Gillies explained.

The physiological mechanism can be exploited by cancers, resulting in malignant tissue and tumors within the body. By manipulating acidity in combination with immunotherapies, this may be able to be managed.

Read the original here:
New Research Explains Why Cancer Cells Often Spread to the Lymph Nodes First - BioSpace

Cell Biology

New type of taste cell discovered in mice – UB News Center

August 24, 2020 medical

Researchers Kathryn Medler (left), University at Buffalo associate professor of biological sciences, and Debarghya Dutta Banik, a UB PhD graduate who is now a postdoctoral fellow at the Indiana University School of Medicine, pictured in 2019 at UB. Credit: Douglas Levere / University at Buffalo

Multitasking taste cells can sense bitter, sweet, sour and umami stimuli, challenging scientists understanding of how taste buds work

Release Date: August 20, 2020

BUFFALO, N.Y. Some taste cells are multitaskers that can detect bitter, sweet, umami and sour stimuli, a new study finds.

The research challenges conventional notions of how taste works. In the past, it was thought that taste cells were highly selective, capable of discerning only one or two types of the five basic stimuli (only sweet, for instance, or only salty and sour). Though many cells are indeed specialists, the discovery of a subset of cells that can respond to up to four different tastes suggests that taste science is more complex than previously thought.

The study was published on Aug. 13 in the journal PLOS Genetics. The research was done on mice, which have a very similar taste system to humans, says Kathryn Medler, PhD, associate professor of biological sciences in the UB College of Arts and Sciences, who led the study with first author Debarghya Dutta Banik.

This changes the way weve been thinking about how taste cells function and how taste information is collected in a taste bud and sent back to the brain, Medler says. Our data fills in a lot of holes. Other research has suggested that taste cells can be broadly responsive, but we were able to isolate individual taste cells and describe how they work. I cannot definitively state that humans have these broadly responsively taste cells, but based on the high degree of similarity between the mouse and human taste systems, I predict that these cells are very likely present in humans.

Most taste cells selectively respond to a specific stimulus type while broadly responsive cells respond to multiple taste qualities. Credit: Jhanna Flora and Kathryn Medler

It is currently believed that taste cells are very specific about what stimuli they detect. The surprising thing with this new cell population is that individual cells can detect bitter, sweet, umami as well as sour stimuli, says Dutta Banik, PhD, a postdoctoral fellow in anatomy, cell biology and physiology in the Indiana University School of Medicine. Dutta Banik did the research while pursuing his doctorate at UB. It was surprising to know that individual taste cells can respond to so many taste qualities.

What happens when these multitasking cells are silenced?

Researchers Ann-Marie Torregrossa, University at Buffalo assistant professor of psychology, and Kathryn Medler, UB associate professor of biological sciences, pictured in 2019. Credit: Douglas Levere / University at Buffalo

Taste cells are critical to survival: They help us decide whether a food is a good source of nutrients or a potential poison.

Beyond identifying the multitasking taste cells, the new study describes some of their traits. Scientists showed that the cells detect sour stimuli using one signaling pathway, and sweet, bitter and umami stimuli using a different pathway.

Experiments also showed that when broadly responsive taste cells are silenced, mice have trouble tasting sweet, bitter and umami stimuli. This was the case even when the more selective taste cells those that specialize in detecting individual stimuli remained active, says study co-author Ann-Marie Torregrossa, PhD, assistant professor of psychology in the UB College of Arts and Sciences and associate director of the Center for Ingestive Behavior Research.

We did a series of taste tests, says Torregrossa, who led the behavioral aspects of the study. When the animals were missing the function of either the broadly responsive cells or of the traditional taste cells, they responded to sweet, bitter and umami solutions as if they were water. This is very exciting because it suggests they needed both cells to taste the solution normally. When we did the same taste tests with animals that had both cells, they as you would expect licked the sweet solution avidly and avoided the bitter.

Researcher Debarghya Dutta Banik works with an imaging system. In the new study, this set-up was used to locate taste cells through fluorescent microscopy. Dutta Banik, a postdoctoral fellow at the Indiana University School of Medicine, is pictured in 2019 at the University at Buffalo, where he completed his PhD. Credit: Douglas Levere / University at Buffalo

This shows that both of these cell populations are important for sending the taste information to the brain, Dutta Banik says.

The groundbreaking findings highlight how much scientists still have to learn about taste, including how taste buds work and send information to the brain.

Compared to other sensory systems, we know surprisingly little about how taste is coded and processed, Torregrossa says. This study identifies a new population of cells that are contributing to normal taste function, which could be a large piece in the puzzle.

The study's co-authors also included Eric D. Benfey, Amy R. Nelson, Zachary C. Ahart, Barrett T. Kemp and Bailey R. Kemp in the UB Department of Biological Sciences; and Laura E. Martin, Kristen E. Kay and Gregory C. Loney in the UB Department of Psychology. The research received support from the UB North Campus Imaging Facility, which is funded by the U.S. National Science Foundation.

Media Contact Information

See the original post here:
New type of taste cell discovered in mice - UB News Center

Cell Biology

Forging molecular bonds with green light – Science Codex

August 24, 2020 medical

Queensland University of Technology (QUT) researchers have created a new molecular coupling tool employing both green light and pH triggers that has potential for use in applications such as drug delivery and 3D cell culture platforms.

Their research has been published in the journal Nature Communications.

The researchers designed photoreactive molecules that enabled them to couple together, using green light as the fuel, polymers commonly used in medical and industrial applications. They then controlled the molecules' photoreactivity by changing pH (the measure of how acid or alkaline a substance is).

It is the first time pH has been used as an on/off switch for a green light-activated, catalyst-free chemical process.

The green light used was also the longest wavelength of light (up to 500 nanometres) employed to date to control a catalyst-free photochemical bond-forming reaction.

To demonstrate the application potential of this photochemical innovation, the team produced a range of hydrogels with varying mechanical properties. Hydrogels are commonly used in contact lenses, tissue engineering scaffolds, as drug delivery carriers, and for cell biology studies.

The research was conducted by lead author and QUT PhD chemistry researcher Kubra Kalayci, Australian Research Council (ARC) DECRA Fellow Dr Hendrik Frisch, Research Fellow Dr Vinh Truong, and ARC Laureate Fellow Professor Christopher Barner-Kowollik from QUT's Soft Matter Materials Laboratory in the Science and Engineering Faculty Centre for Materials Science.

Professor Barner-Kowollik said scientists were constantly seeking to move further away from using harsh UV light to activate chemical reactions.

"Our photochemical innovation is another example of what is called red-shifting - moving through the colours of light in the spectrum, from blue to green towards red, to light that has longer wavelengths," he said.

"In the past, most of these types of photochemical reactions were triggered by harsh UV (ultra-violet) light. But that prevents applications in a biological context because UV light has so much energy it kills cells.

"Dentistry is an example of one of the areas that has shifted. Initially dentists were using UV lamps. Now anyone who has had a filling probably knows that the dentist uses a little lamp with longer wavelength blue light for curing.

"The longer the wavelength of light the better, in principle. The radiation is less harmful, so it can be used for biological applications, and it allows for deeper light penetration. For dentistry, that means better and more uniform curing.

"But it is also more difficult to do, because the longer the wavelength of light the less energy you have to drive the chemical reaction.

"Adding an additional stimulus with the green light, such as we have with varying the pH as a reversible on-off switch for the reaction, provides the opportunity for better regulation. This is especially important for drug delivery systems, where the drug needs to be released under a specific pH, as pH varies throughout the human body.

"This is also a catalyst-free reaction. It means there's no helper molecule to make it happen. That's important for biological application as well because in many cases helper molecules contain metal, and you don't want something that could leach out, or something that is found to be cytotoxic or carcinogenic."

To investigate the new green light-pH coupling tool's suitability for biomaterials engineering, Ms Kalayci said the research team created hydrogels with different properties.

"These showed that green light allowed higher penetration depths, resulting in fabrication of thicker hydrogels," she said.

Dr Truong said cells cultured inside the hydrogels "showed the process for creating the gels was non-toxic, and the cells also remained viable for several days".

The team believes the new coupling tool has a range of other potential applications.

"For example, in the context of personalised medicine," Dr Truong and Dr Frisch said. "You might want to use our reaction to attach a cancer drug to a specific part of a molecule to deliver the drug in a way that is suited to a particular patient."

Professor Barner-Kowollik said it was also another step towards achieving "molecular surgery".

"What chemists hope to do is be able to 'operate' on one part of a molecule without affecting anything else," he said.

"So, for example, if you had a protein, a large complex molecule, we'd like to be able to use light like a chemical scalpel and very delicately go in and change part of that molecule without affecting any other part. That provides many potential applications."

Applications could include, Dr Truong said, "looking at the selective crosslinking of DNA to study the underlying mechanism of a cancer, looking for avenues for targeted treatment, or creating dynamic hydrogel scaffolds to study cell interactions for tissue regeneration therapy.

"Using light, we are providing chemical tools to be able to achieve these aims."

View post:
Forging molecular bonds with green light - Science Codex

Cell Biology

Doctors found a new drug that might block coronavirus infections – BGR

August 24, 2020 medical

Scientists from all over the world have come up with all sorts of ways to fight the novel coronavirus, targeting the pathogen with various existing drugs and new compounds in an attempt to prevent it from infecting cells. Some of these drugs failed in key tests, with hydroxychloroquine being the most prominent failure so far. Others have shown some efficacy, like remdesivir, dexamethasone, and blood thinners. Several new treatments are still in testing and could yield results in the coming months. Its not just vaccines the world needs to end the pandemic, after all. Effective COVID-19 therapies that can significantly reduce complications and deaths are also needed to help those people who will continue to get infected.

Researchers are now studying vacuolin-1 and apilimod, two similar drugs that might be able to block the novel coronavirus from infecting cells.

The drugs arent brand new, Harvard Medical School explains. But theyve been repurposed for treating COVID-19.

Vacuolin-1 and apilimod were developed years ago and they target an enzyme called PIKfyve kinase. This enzyme has a role in the COVID-19 infection, which is why the drugs might work. Tomas Kirchhaused, professor of cell biology in the Blavatnik Institute at HMS and professor of pediatrics at Boston Childrens, discovered vacuolin-1 16 years ago. Apilimod was developed by LAM Therapeutics. The two drugs are similar and they can both block the Ebola virus, researchers found a few years ago. Those studies were continued once the novel coronavirus arrived, as Kirchhausen realized that the kinetics of cell entry in Ebola and COVID-19 are similar.

Published in PNAS, a study on the matter explains that PIKfyve kinase inhibitors could prevent infection from either SARS-CoV-2 or the Zaire ebolavirus.

Our findings show that targeting this kinase through a small-molecule antiviral against SARS-CoV-2 may be an effective strategy to lessen the progression or seriousness of COVID-19, study co-senior author Kirchhausen said. Within a week, we knew apilimod worked extremely well in preventing SARS-CoV-2 infection in human cells in the lab. We found that like apilimod, vacuolin-1 is a very strong inhibitor for viral infection in the lab.

Separately, a paper in Nature published a list of 12,000 clinical-stage or FDA-approved small molecules that could inhibit the replication of the novel coronavirus. Apilimod was one of the drugs included on that list.

AI Therapeutics tested apilimod in Phase 1 and 2 trials for the treatment of autoimmune conditions, but that drug failed to show any efficacy. However, the tests proved the compound did not produce significant side effects even after more than a year of high doses.

The company received FDA approval this spring to see if apilimod can reduce the severity of COVID-19, using data from Kirchhausens early study that was initially published in pre-print form in bioRxiv, as well as other drug screens. AI Therapeutics then announced the start of a randomized, double-blind, placebo-controlled study with apilimod in late July the LAM-002 study.

The drug will be tested on 140 COVID-19 patients, with the company looking to assess its safety, tolerability, and efficacy at reducing the viral load in patients.

Chris Smith started writing about gadgets as a hobby, and before he knew it he was sharing his views on tech stuff with readers around the world. Whenever he's not writing about gadgets he miserably fails to stay away from them, although he desperately tries. But that's not necessarily a bad thing.

Read the original post:
Doctors found a new drug that might block coronavirus infections - BGR

Cell Biology

Commitment to Education and Mentoring: How Memorial Sloan Kettering Continued Summer Internships During the Pandemic – On Cancer – Memorial Sloan…

August 24, 2020 medical

While numerous summerinternships in the United States and abroad were cancelled this year due to the pandemic, Memorial Sloan Kettering (MSK) has kept many internship programs running both virtually and in-person. This summer, more than 300 interns from around the world were enrolled in MSK internship programs and many more students were involved in frequent online seminars and lectures provided by MSK.

Education is one of the core pillars of MSKs mission to lead in the prevention, diagnosis, treatment, and cure of cancer and associated diseases. MSK is dedicated to training the next generation of scientists and healthcare professionals, so when it became apparent in early March that hosting summer interns in-person was going to be uniquely challenging, MSK leaders quickly shifted to modify many of our student summer programs rather than cancel them outright.

At MSK, we are acting on our deep commitment to continue educating studentsduring the pandemic, said Laura Liberman, MD, FACR, Director of the Office of Faculty Development (OFD). Now, more than ever, we see why its vital to train the next generationof scientists and healthcare professionals and to teach them how to communicate clearly and accurately about science and health.

Some programs were modified to make them available to even more students. The Human Oncology and Pathogenesis Program (HOPP) Summer Student Program, designed for high school students who are interested in pursuing careers in the biomedical sciences, shifted to a virtual seminar series open to everyone by registering here. This series, which ends August 28, includes one-hour lectures held up to three times a week from leading doctors and scientists at MSK and other institutions.

A new program was created to focus on COVID-19 specifically. The MSK CARES (Coronavirus Academic Research Experience Summer) Program engaged past interns from the Summer Clinical Oncology Research Experience (SCORE) in literature review and analysis during the pandemic. These 14 SCORE alumni volunteered to join this brand new research program where they explored many aspects of COVID-19, including fatality rates, testing, vaccine development, telehealth, disparities among patient populations, and more. Check out their final presentations here and here.

Throughout the year, MSK hosts more than 25 different student programs that give high school students, college students and recent graduates the opportunity to work alongside our world-renowned staff in a variety of different areas. Some examples of student programs include the Clinical Assistance Program (CAP) for nursing students, Summer Support Internship/Employment Program for students interested in healthcare/hospital administration, Chemical Biology Summer Program (ChBSP) for chemistry, biochemistry, and chemical biology undergraduate students, Summer Exposure Program (SEP) designed to expose underserved high school students to clinical and research opportunities in oncology, and many more programs found here. There are internship opportunities in clinical research, molecular biology, chemical biology, computational biology and medicine, nursing, information technology, healthcare administration, office management, and more.

Get to know a few of our students who joined us this summer:

Anthony Martinez Benitez is a senior at Hunter College, majoring in human biology and minoring in chemistry. When he was seven years old, he and his family moved from El Salvador to Hempstead, NY, where they still reside. He first became interested in pre-med in high school after attending a summer pipeline program at the Zucker School of Medicine at Hofstra University. However, Anthonys specific passion for research started after he participated in our Clinical Oncology Open Learning (COOL) Scholars Program. After learning about the many types of physiological and psychological effects on cancer patients through this program, he was inspired to seek out research laboratories that focus on studying the advancement of cancer. This brought Anthony to apply to the SCORE Program this summer. He has been working virtually from home, and presented his final project on the STAG2 gene, which is found to be commonly mutated in bladder cancer (and several other types of cancer). In his free time, Anthony volunteers at a local hospital. After he graduates, he hopes to join one of MSKs research labs to continue to gain research experience and someday become a physician-scientist.

Rachelle Monteau is a pre-med student at CUNY in the highly competitive Sophie Davis Biomedical Education Program, a seven-year BS/MD program that specifically recruits students from underrepresented populations into medicine. Rachelles parents are originally from Haiti, but they now live in Queens, where she has been conducting her internship virtually this summer. Inspired by her father who is a physician assistant, she hopes to bring her medical training to underrepresented communities in the United States and abroad when she graduates. Rachelle was also accepted to our SCORE Program this summer, where she worked with her mentor, Fumiko Chino, MD, on her final project focused on racial trends in liver cancer mortality.

Kathleen Navasis a senior at UC Berkeley, double majoring in data science andMCB (Molecular and Cell Biology) with a focus on immunology. Shes spent her whole life living in the Bay Area, but in late June she travelled to New York City for the first time to work inThe Quaid Morris Lab. Out of a cohort of thirteen inourComputational Biology Summer Program (CBSP), she is one of three interns working on-site. Kathleen is focusing on multiple projects, including investigating how new onset autoimmunity can inform cancer outcome predictions. While she admits that its a strange time to live in New York City (but a great time to jog across town and sightsee unusually empty locations, including Times Square!), she will be staying through the fall to continue working on her research.

Amelia Tran lives in Vietnam and has been conducting herinternship from there this summer working opposite hours on East Coast time! She is a senior at Mount Holyoke College in Massachusetts majoring in statistics. This summer, she was an intern in the Quantitative Sciences Undergraduate Research Experience (QSURE) program, where she learned about the role of statistics in biomedical settings. She is grateful that her internship was not cancelled, and found that the program was still well organized and professional, even though it was all virtual. She and her fellow QSURE interns still keep in touch over WhatsApp.

For more information about internships and student and new-grad careers at MSK, please visit: https://careers.mskcc.org/students-new-grads/.

Continue reading here:
Commitment to Education and Mentoring: How Memorial Sloan Kettering Continued Summer Internships During the Pandemic - On Cancer - Memorial Sloan...

Cell Biology

Online Peer Support: Supportiv Whitepaper Reveals Evidence-Based Solution To Mental Health Epidemic – PR Web

August 24, 2020 medical

Supportiv Peer Support Whitepaper

BERKELEY, Calif. (PRWEB) August 24, 2020

During the COVID-19 pandemic, employers and health insurers are grappling with mental well-being issues that have long affected their employees and members, but have now risen to a boiling point: loneliness, social isolation, anxiety, depression, and day-to-day stress are all peaking. To cost-effectively solve these long-standing mental health and wellness challenges, look to evidence-based, scalable, affordable solutions like peer support.

Supportiv, the peer support network, has released a whitepaper synthesizing 120 existing research studies on the unique role peer support can play in improving individual mental health and physical health outcomes. Positive clinical outcomes from the novel mental health solution are discussed in the paper, written by Dr. Rosemary Ku, a physician with dual board certifications in Internal Medicine and Preventative Medicine.

Dr. Ku completed her undergraduate education in Neuroscience and Molecular/Cell Biology at Princeton, and her MD at Columbia University. In addition, shes an expert on the intersection of public health and novel technology solutions, having earned an MBA from Columbia, and a Masters in Public Health from UC Berkeley. As she summarizes in the paper:

The healthcare system is designed to intervene when conditions become severe and is not equipped to address the challenges of daily life struggles. Peer support has been identified as an effective intervention to fill this gap, instill greater emotional well-being, and improve health outcomes for a wide range of mental and physical health issues. By increasing social connectedness and providing both emotional and tactical support for day-to-day stressors, peer support is a low-cost, effective service that can serve as a standalone offering or complementary to disease management programs.

What is not widely known are the studied outcomes of peer support vis-a-vis traditional forms of mental health care. The whitepaper cites a meta-analysis of randomized control trials (RCTs) that compared peer support to traditional care for depression, in which peer support was significantly more effective for reducing depression scores. Further, peer support was as effective as group cognitive behavioral therapy (CBT). The magnitude of improvement seen from peer support was similar to those of psychotherapy and antidepressant medications.

The whitepaper addresses accessibility advantages of online peer support networks, in a time when low-cost, accessible, flexible, and scalable care is critical to employers, health plans, individual end users, and U.S. public health system.

Online peer support has the potential to integrate with other value-adding features, unlike its in-person counterpart. For example, Supportivs 24/7 digital peer-to-peer support chat platform surfaces resources, self-help tips, referrals and recommendations, all in real-time inside. By typing a few words in response to the question: Whats your struggle? users are matched in under a minute to topic-specific peer-to-peer small group chats that are professionally moderated for safe, anonymous support. Users receive instant compassion from others who relate to their struggles, as well as practical self-help tools on topics from communication conflict, parenting challenges, or burnout to loneliness, anxiety, and depression.

When evaluating an online peer support program, be sure your selection operates on evidence-based principles, notes Dr. Ku. Some further relevant considerations include:

Online peer support can help people process, cope, or heal from emotional struggles in ways that traditional mental healthcare options simply cannot achieve. Uses come away feeling more hopeful and empowered to take action.

Supportiv has already enabled over 550,000 users to feel less lonely, anxious, stressed, misunderstood, and hopeless through its moderator-guided chats with AI-driven content and resource recommendations. The peer support network is available 24 hours a day at http://www.supportiv.com.

Share article on social media or email:

Go here to read the rest:
Online Peer Support: Supportiv Whitepaper Reveals Evidence-Based Solution To Mental Health Epidemic - PR Web

Cell Biology

Using engineered off-the-shelf therapeutic T cells to fight cancer – News-Medical.net

August 24, 2020 medical

Reviewed by Emily Henderson, B.Sc.Aug 20 2020

Personalized cancer treatments are no longer just options of the future. In the past few years, researchers have made significant progress in 'teaching' the body's immune T cells to recognize and kill specific cancer cells, and human clinical trials have shown that this approach can successfully eliminate tumors.

Cancer patients today can be a part of the following clinical scenario: a patient comes to the hospital where physicians and scientists analyze his or her tumor to identify cancer-specific markers that would serve as targets for the novel therapy. Blood is drawn from the patient and sent to Baylor College of Medicine's Center for Cell and Gene Therapy where the immune T cells are transformed into cells with a mission to identify and kill cells with the tumor-specific tags. The final cells are infused back into the patient to complete their job.

At the Center, we genetically engineer the patient's T cells to arm them with the tools they need to identify the patient's tumor-specific markers and eliminate the cancer."

Dr. Maksim Mamonkin, assistant professor of pathology & immunology and member of the Center for Cell and Gene Therapy at Baylor

Although this treatment can effectively eliminate tumors, the 'training' of the T cells is complex and expensive. "Sometimes, the trained T cells are not highly potent because the patient already received a number of treatments that weakened the immune cells we work with," Mamonkin said.

In addition, the process to manufacture the therapeutic T cells is time consuming. "Sometimes it takes weeks to get the T cells ready, and in this time the patient may take a turn for the worse," Mamonkin said.

"Now that we know that this type of cell immunotherapy has a lot of promise, the next step is to streamline it, make it more accessible and make sure that the resulting T cells have the highest potency," said Mamonkin, who also is a member of the Dan L Duncan Comprehensive Cancer Center.

Researchers are developing ready-to-use, off-the-shelf therapeutic T cells. These are genetically engineered T cells that are manufactured from normal, healthy donors. The cells are expanded and well characterized, and have shown to be effective at killing cancer cells. The cells are cryo-preserved - stored frozen in liquid nitrogen - until it's time to use them. In this scenario, a cancer patient comes to the hospital and the tumor markers are identified. Then, with the identity of the tumor-specific tags in hand, the physician goes to a room filled with large below-zero freezers searching for the one that holds little containers with healthy immune T cells that have been genetically engineered to recognize and destroy cells with the patient's cancer-specific markers. These 'off-the-shelf,' ready-made cells are thawed, prepared and infused into the patient several days later.

"This approach solves two limitations of the original approach: it avoids the time-consuming, elaborate steps of training and expanding the patient's cells and results in therapeutic T cells of higher potency," Mamonkin said. "However, the novel approach presents a new set of limitations."

One of the limitations of the off-the-shelf approach emerges when the therapeutic T cells enter the patient's body. The patient's own immune system recognizes the cells as foreign, such as it happens with organ transplants, and may reject the therapeutic cells.

"This is a major problem because rejection not only would reduce the duration of the T cells activity against the tumor, but also would preclude giving subsequent doses of cells. The immune system would reject subsequent doses of the cells right way," said first author, Feiyan Mo, graduate student in Mamonkin's lab. "To solve this problem we thought that the best defense was a good offense." The researchers gave the therapeutic T cells a tool that would enable them to fight back the attack of the patient's immune cells against them. They genetically engineered the therapeutic T cells to express a receptor called alloimmune defense receptor, or ADR. ADR recognizes a specific molecule, called 4-1BB, that is only expressed on the patient's activated T cells and natural killer (NK) cells that would attack them. 4-1BB is not expressed on resting T and NK cells that do not turn against the therapeutic T cells.

"Both experiments in the lab and animal models with blood cancers or solid tumors showed that ADR protected off-the-shelf therapeutic T cells from being rejected," Mo said. "Not only did they resist rejection, but they also expanded more and persisted longer than therapeutic T cells without ADR." The researchers are optimistic that this approach may also work in patients. They plan to conduct clinical trials on 2021.

"If successful, this approach can be extended to targeting other disease-causing T-cells, such as those rejecting transplanted organs, mediating graft-versus-host disease or perpetuating autoimmunity," said Mamonkin. "We are very excited to develop this concept for several applications beyond cancer therapy." This technology has been licensed to Fate Therapeutics, a clinical-stage biopharmaceutical company that plans on integrating ADR into their clinical products.

"The BCM Ventures team is very pleased to partner with Fate Therapeutics in a licensing relationship to support their implementation of the ADR technology developed in the Mamonkin laboratory here at BCM. This approach promises to enhance the effectiveness of off-the-shelf cell therapies, and it will now be used more extensively in the clinical setting which stands to benefit patients," said Michael Dilling, director of Baylor Licensing Group. "BCM has been an innovator in the development of cell therapies and the commercial sector increasingly looks to BCM as a source for new innovations."

Feiyan Mo, who took the lead on this work, has received an NIH NCI F99/F00 Predoctoral-to-postdoctoral Fellowship Award to help facilitate the translation of ADR to the clinic and continue postdoctoral studies in cancer biology. She is a Baylor graduate student and is co-mentored by Drs. Mamonkin, Malcolm Brenner and Helen Heslop. Are you interested in learning all the details of this work? Find them in the journal Nature Biotechnology.

Source:

Journal reference:

Mo, F., et al. (2020) Engineered off-the-shelf therapeutic T cells resist host immune rejection. Nature Biotechnology. doi.org/10.1038/s41587-020-0601-5.

See more here:
Using engineered off-the-shelf therapeutic T cells to fight cancer - News-Medical.net

Cell Biology

New tools catch and release cellular targets at the flip of a light switch – Princeton University

August 22, 2020 medical

A Princeton team has developed a class of light-switchable, highly adaptable molecular tools with new capabilities to control cellular activities. The antibody-like proteins, called OptoBinders, allow researchers to rapidly control processes inside and outside of cells by directing their localization, with potential applications including protein purification, the improved production of biofuels, and new types of targeted cancer therapies.

This time-lapse movie shows a new tool called an OptoBinder that can latch onto and release molecules in response to light. In this case, a fluorescent OptoBinder is attaching to actin, a component of cells key to their structure and shape. The OptoBinder strongly binds to actin in the dark, but releases its hold in the presence of blue light (indicated by blue box at top right).

Video courtesy of the researchers; GIF by Bumper DeJesus

In a pair of papers published Aug. 13 in Nature Communications, the researchers describe the creation of OptoBinders that can specifically latch onto a variety of proteins both inside and outside of cells. OptoBinders can bind or release their targets in response to blue light. The team reported thatone type of OptoBinderchanged its affinity for its target molecules up to 330-fold when shifted from dark to blue light conditions, whileothersshowed a five-fold difference in binding affinity all of which could be useful to researchers seeking to understand and engineer the behaviors of cells.

Crucially, OptoBinders can target proteins that are naturally present in cells, and their binding is easily reversible by changing light conditions a new capability that is not available to normal antibodies, said co-authorJos Avalos, an assistant professor ofchemical and biological engineeringand theAndlinger Center for Energy and the Environment. The ability to let go [of a target protein] is actually very valuable for many applications, said Avalos, including engineering cells metabolisms, purifying proteins or potentially making biotherapeutics.

The new technique is the latest in a collaboration between Avalos andJared Toettcher, an assistant professor ofmolecular biology. Both joined the Princeton faculty in 2015, and soon began working together on new ways to applyoptogenetics a set of techniques that introduce genes encoding light-responsive proteins to control cells behaviors.

We hope that this is going to be the beginning of the next era of optogenetics, opening the door to light-sensitive proteins that can interface with virtually any protein in biology, either inside or outside of cells, said Toettcher, the James A. Elkins, Jr. 41 Preceptor in Molecular Biology.

The research team included (from left) Jos Avalos, an assistant professor of chemical and biological engineering and the Andlinger Center for Energy and the Environment; associate research scholar Csar Carrasco-Lpez; assistant professor of molecular biology Jared Toettcher; and postdoctoral research fellow Agnieszka Gil.

Avalos and his team hope to use OptoBinders to control the metabolisms of yeast and bacteria to improve the production of biofuels and other renewable chemicals, while Toettchers lab is interested in the molecules potential to control signaling pathways involved in cancer.

The two papers describe different types of light-switchable binders: opto-nanobodies and opto-monobodies. Nanobodies are derived from the antibodies of camelids, the family of animals that includes camels, llamas and alpacas, which produce some antibodies that are smaller (hence the name nanobody) and simpler in structure than those of humans or other animals.

Nanobodies small size makes them more adaptable and easier to work with than traditional antibodies; they recently received attention for their potential as a COVID-19 therapy. Monobodies, on the other hand, are engineered pieces of human fibronectin, a large protein that forms part of the matrix between cells.

These papers go hand in hand, said Avalos. The opto-nanobodies take advantage of the immune systems of these animals, and the monobodies have the advantage of being synthetic, which gives us opportunities to further engineer them in different ways.

The two types of OptoBinders both incorporate a light-sensitive domain from a protein found in oat plants.

When you turn the light on and off, these tools bind and release their target almost immediately, so that brings another level of control that was not previously possible, said co-author Csar Carrasco-Lpez, an associate research scholar in Avalos lab. Whenever you are analyzing things as complex as metabolism, you need tools that allow you to control these processes in a complex way in order to understand what is happening.

In principle, OptoBinders could be engineered to target any protein found in a cell. With most existing optogenetic systems, you always had to genetically manipulate your target protein in a cell for each particular application, said co-author Agnieszka Gil, a postdoctoral research fellow in Toettchers lab. We wanted to develop an optogenetic binder that did not depend on additional genetic manipulation of the target protein.

In a proof of principle, the researchers created an opto-nanobody that binds to actin, a major component of the cytoskeleton that allows cells to move, divide and respond to their environment. The opto-nanobody strongly bound to actin in the dark, but released its hold within two minutes in the presence of blue light. Actin proteins normally join together to form filaments just inside the cell membrane and networks of stress fibers that traverse the cell. In the dark, the opto-nanobody against actin binds to these fibers; in the light, these binding interactions are disrupted, causing the opto-nanobody to scatter throughout the cell. The researchers could even manipulate binding interactions on just one side of a cell a level of localized control that opens new possibilities for cell biology research.

OptoBinders stand to unlock scores of innovative, previously inaccessible uses in cell biology and biotechnology, said Andreas Mglich, a professor of biochemistry at the University of Bayreuth in Germany who was not involved in the studies. But, Mglich said, there is much more to the research because the design strategy can be readily translated to other molecules, paving the way to an even wider repertoire of customized, light-sensitive binders.

The impressive results mark a significant advance, he said.

Future applications will depend on being able to generate more OptoBinders against a variety of target proteins, said Carrasco-Lpez. We are going to try to generate a platform so we can select OptoBinders against different targets using a standardized, high-throughput protocol, he said, adding that this is among the first priorities for the team as they resume their experiments after lab research was halted this spring due to COVID-19.

Beyond applications that involve manipulating cell metabolism for microbial chemical production, Avalos said, OptoBinders could someday be used to design biomaterials whose properties can be changed by light.

The types of OptoBinders developed by postdoctoral research fellow Agnieszka Gil and colleagues could in principle be engineered to target any protein in a cell, opening new possibilities for fundamental research, biofuel production and therapeutics.

The technology also holds promise as way to reduce side effects of drugs by focusing their action to a specific site in the body or adjusting dosages in real time, said Toettcher, who noted that applying light inside the body would require a device such as an implant. There arent many ways to do spatial targeting with normal pharmacology or other techniques, so having that kind of capability for antibodies and therapeutic binders would be a really cool thing, he said. We think of this as a sea change in what sorts of processes can be placed under optogenetic control.

Other authors on the opto-monobody paper were Evan Zhao, who earned a Ph.D. in chemical and biological engineering from Princeton in 2019; and Nathan Alam, an undergraduate from the Class of 2021. Zhao was also a co-author on the opto-nanobody paper, along with Liyuan Zhu, a graduate student in the Department of Chemistry; Pavithran Ravindran, a research specialist in molecular biology; Maxwell Wilson, a former associate research scholar in molecular biology who is now an assistant professor at the University of California-Santa Barbara; and Alexander Goglia, a medical student in the Robert Wood Johnson Medical School and Princeton University M.D./Ph.D. program.

The work was supported in part by the U.S. National Institutes of Health, National Science Foundation and Department of Energy; the Pew Charitable Trusts; and the Eric and Wendy Schmidt Transformative Technology Fund.

Cell Biology

Covid-19 Impact on Global Cell Biology Cloud Computing Market 2020 by Company, Type and Application, Forecast to 2025 – The Daily Chronicle

August 22, 2020 medical

Global Cell Biology Cloud Computing Market 2020 by Company, Type and Application, Forecast to 2025 published on MarketQuest.biz offers an extremely intelligent and deep assessment of the present market condition along with the overall market size, share, and dynamics estimated from 2020 to 2025. The report showcases a comprehensive analysis of the leading business programs, future market, and business-oriented planning. The report sheds light on changing market scenarios and initial and future assessments of the global Cell Biology Cloud Computing market. It investigates desirable factors related to market situations such as growth rates, demands, and differentiable business-oriented strategies used by the market manufacturers with respect to distinct tactics and the futuristic prospects in brief.

The report then covers gives a detailed overview of global Cell Biology Cloud Computing industry prime vendors and regional evaluation with forecast period 2020 to 2025. The research focuses on primary and secondary drivers, market share, leading segments, and regional analysis. It also delivers the market competitive landscape and an elementary inspection of the regional growth of the market. It also provides analysis pertaining to the global market trends, growth, as well as major collaborations, merger & acquisitions along with upcoming and trending innovation. The report comprises the assessment of cost and pricing operating in the specific geographies. Graphs are used to support the data format for a clear understanding of facts and figures.

DOWNLOAD FREE SAMPLE REPORT: https://www.marketquest.biz/sample-request/24282

NOTE: Our analysts monitoring the situation across the globe explains that the market will generate remunerative prospects for producers post COVID-19 crisis. The report aims to provide an additional illustration of the latest scenario, economic slowdown, and COVID-19 impact on the overall industry.

Companies profiled and studied for this market report include: Accenture, Oracle, Cisco Systems, Amazon Web Services, DXC Technology, Benchling, IPERION, IBM, Dell Emc, ScaleMatrix, NovelBio

The report further provides the new and existing players in the global Cell Biology Cloud Computing market with information such as company profiles, facts and figures, product pictures and specifications, sales, market share, and contact information. It covers segments such as competitor segment, product type segment, end use/application segment, and geography segment. The report utilizes a series of analytical tools including Porters five forces analysis, SWOT analysis, feasibility study as well as the survey of the investment return.

Market segmentation, on the basis of types: Public Cloud Computing, Private Cloud Computing, Hybrid Cloud Computing

Market segmentation, on the basis of applications: Genomics, Diagnostics, Clinical Trials, Pharma Manufacturing, Others

Geographically, the detailed analysis of consumption, revenue, global Cell Biology Cloud Computing market share and growth rate, historic and forecast (2015-2025) of the following regions are covered: North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India and Southeast Asia), South America (Brazil, Argentina, etc.), Middle East & Africa (Saudi Arabia, Egypt, Nigeria and South Africa)

ACCESS FULL REPORT: https://www.marketquest.biz/report/24282/global-cell-biology-cloud-computing-market-2020-by-company-type-and-application-forecast-to-2025

Key Features of the Global Market Report:

Customization of the Report:

This report can be customized to meet the clients requirements. Please connect with our sales team ([emailprotected]), who will ensure that you get a report that suits your needs. You can also get in touch with our executives on +1-201-465-4211 to share your research requirements.

About Us

MarketQuest.biz is a leading global Market Research agency providing expert research solutions, trusted by the best. We understand the importance of knowing what global consumers watch and buy, further using the same to document our distinguished research reports. MarketQuest.biz has worldwide presence to facilitate real market intelligence using latest methodology, best-in-class research techniques and cost-effective measures for worlds leading research professionals and agencies. We study consumers in more than 100 countries to give you the most complete view of trends and habits worldwide. MarketQuest.biz is a leading provider of Full-Service Research, Global Project Management, Market Research Operations and Online Panel Services.

Contact UsMark StoneHead of Business DevelopmentPhone: +1-201-465-4211Email: [emailprotected]Web: http://www.marketquest.biz

Read the original here:
Covid-19 Impact on Global Cell Biology Cloud Computing Market 2020 by Company, Type and Application, Forecast to 2025 - The Daily Chronicle

Cell Biology

Better Tool Created to Aid COVID-19 Diagnosis – SciTechDaily

August 22, 2020 medical

An LSU Health New Orleans radiologist and evolutionary anatomist have teamed up to show the same techniques used for research on reptile and bird lungs can be used to help confirm the diagnosis of COVID-19 in patients. Their paper published in BMJ Case Reports demonstrates that 3D models are a strikingly clearer method for visually evaluating the distribution of COVID-19-related infection in the respiratory system. Credit: LSU Health New Orleans

A Louisiana State University Health New Orleans radiologist and evolutionary anatomist have teamed up to show the same techniques used for research on reptile and bird lungs can be used to help confirm the diagnosis of COVID-19 in patients. Their paper published in BMJ Case Reports demonstrates that 3D models are a strikingly clearer method for visually evaluating the distribution of COVID-19-related infection in the respiratory system.

Emma R. Schachner, PhD, Associate Professor of Cell Biology & Anatomy, and Bradley Spieler, MD, Vice Chairman of Radiology Research and Associate Professor of Radiology, Internal Medicine, Urology, & Cell Biology and Anatomy at LSU Health New Orleans School of Medicine, created 3D digital models from CT scans of patients hospitalized with symptoms associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2).

Three patients who were suspected of having COVID-19 underwent contrast enhanced thoracic CT when their symptoms worsened. Two had tested positive for SARS-CoV-2, but one was reverse transcription chain reaction (RT-PCR) negative. But because this patient had compelling clinical and imaging, the result was presumed to be a false negative.

An array of RT-PCR sensitivities has been reported, ranging from 30-91%, notes Dr. Spieler. This may be the result of relatively lower viral loads in individuals who are asymptomatic or experience only mild symptoms when tested. Tests performed when symptoms were resolving have also resulted in false negatives, which seemed to be the result in this case.Given diagnostic challenges with respect to false negative results by RT-PCR, the gold standard for COVID-19 diagnostic screening, CT can be helpful in establishing this diagnosis. Importantly, these CT features can range in form and structure and appear to correlate with disease progression. This allows for 3D segmentation of the data in which lung tissue can be volumetrically quantified or airflow patterns could be modeled.

The CT scans were all segmented into 3D digital surface models using the scientific visualization program Avizo (Thermofisher Scientific) and techniques that the Schachner Lab uses for evolutionary anatomy research.The full effect of COVID-19 on the respiratory system remains unknown, but the 3D digital segmented models provide clinicians a new tool to evaluate the extent and distribution of the disease in one encapsulated view, adds Spieler. This is especially useful in the case where RT-PCR for SARS-CoV-2 is negative but there is strong clinical suspicion for COVID-19.

To date, there havent been good models of what COVID is doing to the lungs. So, this project focused on the visualization of the lung damage in the 3D models as compared to previous methods that have been published volume-rendered models and straight 2D screen shots of CT scans and radiographs.Previously published 3D models of lungs with COVID-19 have been created using automated volume rendering techniques, says Dr. Schachner. Our method is more challenging and time-consuming, but results in a highly accurate and detailed anatomical model where the layers can be pulled apart, volumes quantified, and it can be 3D printed.

The three models all show varying degrees of COVID-19 related infection in the respiratory tissues particularly along the back of the lungs, and bottom sections. They more clearly show COVID-19-related infection in the respiratory system compared to radiographs (x-rays), CT scans, or RT-PCR testing alone. Schachner and Spieler are now segmenting more models for a larger follow-up project.

Reference: Three-dimensional (3D) lung segmentation for diagnosis of COVID-19 and the communication of disease impact to the public by Emma R Schachner and Bradley Spieler, 18 August 2020, BMJ Case Reports.DOI: 10.1136/bcr-2020-236943

Link:
Better Tool Created to Aid COVID-19 Diagnosis - SciTechDaily