Category Archives: Cell Biology

New algorithm provides a high-definition analysis of genome organization in single cells – News-Medical.net

October 12, 2021 medical

Within the microscopic boundaries of a single human cell, the intricate folds and arrangements of protein and DNA bundles dictate a person's fate: which genes are expressed, which are suppressed, and -; importantly -; whether they stay healthy or develop disease.

Despite the potential impact these bundles have on human health, science knows little about how genome folding happens in the cell nucleus and how that influences the way genes are expressed. But a new algorithm developed by a team in Carnegie Mellon University's Computational Biology Department offers a powerful tool for illustrating the process at an unprecedented resolution.

The algorithm, known as Higashi, is based on hypergraph representation learning -; the form of machine learning that can recommend music in an app and perform 3D object recognition.

School of Computer Science doctoral student Ruochi Zhang led the project with Ph.D. candidate Tianming Zhou and Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology. Zhang named Higashi after a traditional Japanese sweet, continuing a tradition he began with other algorithms he developed.

He approaches the research with passion but also with a sense of humor sometimes."

Jian Ma, the Ray and Stephanie Lane Professor of Computational Biology

Their research was published in Nature Biotechnology and was conducted as part of a multi-institution research center seeking a better understanding both of the three-dimensional structure of cell nuclei and how changes in that structure affect cell functions in health and disease. The $10 million center was funded by the National Institutes of Health and is directed by CMU, with Ma as its lead principal investigator.

The algorithm is the first tool to use sophisticated neural networks on hypergraphs to provide a high-definition analysis of genome organization in single cells. Where an ordinary graph joins two vertices to a single intersection, known as an edge, a hypergraph joins multiple vertices to the edge.

Chromosomes are made up of a DNA-RNA-protein complex called chromatin that folds and arranges itself to fit inside the cell nucleus. The process influences the way genes are expressed by bringing the functional elements of each ingredient closer together, allowing them to activate or suppress a particular genetic trait.

The Higashi algorithm works with an emerging technology known as single-cell Hi-C, which creates snapshots of chromatin interactions occurring simultaneously in a single cell. Higashi provides a more detailed analysis of chromatin's organization in the single cells of complex tissues and biological processes, as well as how its interactions vary from cell to cell. This analysis allows scientists to see detailed variations in the folding and organization of chromatin from cell to cell -; including those that may be subtle, yet important in identifying health implications.

"The variability of genome organization has strong implications in gene expression and cellular state," Ma said.

The Higashi algorithm also allows scientists to simultaneously analyze other genomic signals jointly profiled with single-cell Hi-C. Eventually, this feature will enable expansion of Higashi's capability, which is timely given the expected growth of single-cell data Ma expects to see in coming years through projects such as the NIH 4D Nucleome Program his center belongs to. This flow of data will create additional opportunities to design more algorithms that will advance scientific understanding of how the human genome is organized within the cell and its function in health and disease.

"This is a fast-moving area," Ma said. "The experimental technology is advancing rapidly, and so is the computational development."

Source:

Journal reference:

Zhang, R., et al. (2021) Multiscale and integrative single-cell Hi-C analysis with Higashi. Nature Biotechnology. doi.org/10.1038/s41587-021-01034-y.

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New algorithm provides a high-definition analysis of genome organization in single cells - News-Medical.net

Cell Biology

Trigger your skin to heal itself with these beauty products – fox13now.com

October 12, 2021 medical

This summer we introduced you to Augustinus Bader, a skincare brand with dozens of beauty industry awards and countless, A-list celebrity fans. Well, now theres some big news from the brand and beauty writer and editor Cheryl Kramer Kaye shared the news with us.

Augustinus Bader is a real personhes a professor, a physician, and an expert in the field of stem cell biology.

Professor Bader has spent over 30 years researching and developing technologies that activate the bodys healing process, which led him to create the groundbreaking technology behind his skincare line. Its called TFC8 or Trigger Factor Complex 8 because it triggers your skin to heal itself.

By popular demand, Augustinus Bader is launching two new products: The Serum and The Eye Cream.

Both of the products have the TFC8 technology, plus ingredients that both protect and repair the skin to deliver real results. The serum has edelweiss extract for lifting and tightening; pomegranate seed concentrate for cell renewal; and vitamin C for brightening.

And the eye cream has a duo of seaweed extracts to minimize puffiness and dark circles; pennywort extract for hydration and protection against environmental damage; and niacinamide, to protect against UV, pollution, even blue light.

The textures of these products are beautifully lightweight and fast-absorbing, but also incredibly hydrating.

For more information or to order the products go to augustinusbader.com

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Trigger your skin to heal itself with these beauty products - fox13now.com

Cell Biology

Advances in Assisted Reproduction: What Can We Expect? – BioNews

October 12, 2021 medical

11 October 2021

Digital Media and Content Specialist, International Livestock Research Institute

The UK Government recently announced its intention to extend the maximum storage limit, for frozen eggs, sperm and embryos, to 55 years across the board (see BioNews 1111). Sarah Norcross, director of the Progress Educational Trust (PET), invited the audience at PET's event 'Advances in Assisted Reproduction: What Can We Expect?' to consider where assisted reproductive technologies (ART) stood 55 years ago. The first IVF baby hadn't even been born. Norcross mused: 'Where will ART be 55 years from now?'

First speaker, Rod Mitchell, professor of developmental endocrinology at the University of Edinburgh, talked about current advances in ART for males. Patients who are unable to produce sperm don't have the option of freezing it for future use. Such patients include children who receive medical treatment that also damages their fertility, such as chemotherapy.

Professor Mitchell explained that we might instead preserve spermatogonial stem cells, as these are present in children as well as adults. This could be achieved by removing and freezing small portions of testicular tissue, where the stem cells are located. In the future, the sperm could be transplanted back into the testes, or used to produce mature sperm in the lab. Such tissue transplantation research is currently on the cusp of clinical development, having recently proved successful in primates.

Professor Mitchell called for clinicians to ensure good service for the so-called 'inbetweeners' young people who fall between the stage where only spermatogonial stem cells can be harvested, and the stage where mature sperm are present. There are also avenues of research, currently being pursued in animal studies, which could lead to ways of generating sperm that do not need to start from spermatogonial stem cells at all.

Second speaker, Evelyn Telfer, professor of reproductive biology at the University of Edinburgh, addressed advances in the maturation of human eggs in the lab, an area which has been pioneered by her research group. She put her group's research into context with a striking fact: a woman's full egg reserve is entirely formed before birth, but only 0.1 percent of those eggs will ever be ovulated. The rest are lost. This begs the question of whether it is possible to preserve any of the lost 99.9 percent.

In the 1990s, researchers at the University of Edinburgh developed the cryopreservation of ovarian tissue containing immature egg follicles. Since then, more than 130 babies have been born worldwide following transplantation of such ovarian tissue. However, Professor Telfer cautioned that this approach is not suitable for all patients for example, patients with ovarian cancer cannot risk having ovarian tissue removed and transplanted back into the body following treatment, in case the tissue contains malignant cells. This is why the alternative in vitro growth of eggs is needed.

Professor Telfer's group has shown that human eggs can be brought to full maturity using this approach, and she now intends to ensure that the resulting eggs are viable and safe for use. Studies of lab-grown sheep eggs will begin next year. Professor Telfer's group is also investigating how to adapt the maturation process with ovarian tissue obtained from children, from transgender patients, and from patients with chromosomal conditions such as Turner syndrome. Professor Telfer speculated that patients storing tissue now might benefit from future advances, such as the prospect of making mini-ovaries and new eggs from ovarian stem cells.

Third speaker, Adle Marston, professor of cell biology at the University of Edinburgh, talked about one of the major causes of infertility and miscarriage eggs that have an abnormal chromosome number, a phenomenon known as aneuploidy. Some 30-40 percent of eggs are thought to be aneuploid, in contrast to 2 percent of sperm. The likelihood of aneuploidy increases with age, and this contributes to a greater chance of miscarriage if women become pregnant in their 40s.

Aneuploidy occurs during meiosis, the process of cell division which creates eggs in biological females or sperm in males. Professor Marston outlined the process, explaining that immature eggs are 'held' in an early stage, each with an accompaniment of proteins to eventually help sort and divide the chromosomes. The deterioration of these 'sorting proteins' over a woman's lifetime may be one of the reasons why aneuploidy occurs. Professor Marston expects that research using embryos and gametes donated by ART patientswill help us understand more about aneuploidy, and ultimately that knowledge will be used to provide better choices for patient treatment.

The final speaker, David Albertini, professor of developmental cell biology at the Bedford Research Foundation, Massachusetts, gave a historical perspective on ART. Before 2010, many fundamental discoveries in fertility science started with research in animals, and new technologies moved steadily from bench to bedside. The past decade, however, has seen a steady rise in the prominence of 'add-ons' optional treatments which purport to improve ART outcomes.

Professor Albertini used this as an example of the science of human reproduction being drawn further into the realm of big business. He also discussed the advent of new frontiers and additional avenues of research, such as genome editing, which in turn give rise to new ethical challenges.

Professor Albertini said that wide-ranging ethical conversations were long overdue, drawing a link between the commercialisation of reproductive technologies, public mistrust of scientists, and fears of a dystopian future society. New technologies could potentially be used for the selection or even the enhancement of human embryos.

Fertility research is now looking at how to make viable gametes from different types of stem cells. Genome editing is set to become more precise. It is now possible to produce embryos containing mitochondrial DNA from a donor. Although this technology was developed to avoid the transmission of mitochondrial disease, some have sought to adapt it into a fertility treatment.

Professor Albertini concluded that ART have much to be proud of nearly ten million babies have born but argued that it is time to think about the future of this technology, and its potential both to help and to harm.

After the speakers had finished, there was no shortage of questions from the audience. Some attendees asked whether it was medically or ethically justifiable to have children at the far end of the 55-year storage limit. Professor Telfer said it was unlikely that people would choose to become parents at advanced ages, while Professor Mitchell reminded the audience that gametes or reproductive tissue from very young patients are sometimes being stored, in which case long storage periods are justified.

It was also asked whether science could help a woman with a low number of eggs generate new eggs. Professor Albertini said that while there research into this possibility, the results so far are not promising. It is more feasible to help immature egg follicles mature in the ovary than it is to produce entirely new eggs.

One attendee asked whether cryopreservation affects chromosome stability and meiosis. Professor Marston responded that we still lack an adequate understanding of what the 'normal' appearance of chromosomes in healthy eggs is. Professor Telfer agreed that the science surrounding egg freezing had not advanced as much as is sometimes assumed there are still many questions to be answered about different techniques, and how freezing affects development.

Further questions covered the low complication rate of egg and sperm collection processes, and what could be done in the future about premature menopause. Professor Albertini reflected that there are now options to preserve fertility that didn't exist 20 years previously, and added that while premature menopause is characterised by substantial and early loss of eggs, ovaries with low egg reserve can still be stimulated to produce eggs for freezing.

As the event drew to a close, a final question concerned whether there is a difference in fertility preservation approaches between the sexes. Professor Mitchell said that there wasn't, except in the sense that research into male fertility lags 20 years behind research into female fertility.

Throughout the event, the speakers struck a careful balance between honest caution and excitement about new possibilities.

PET is grateful to the Scottish Government for supporting this event. Our next online events will be:

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Advances in Assisted Reproduction: What Can We Expect? - BioNews

Cell Biology

Bone Therapeutics appoints Scientific Advisory Board for iMSC cell and gene therapy platform development – StreetInsider.com

October 12, 2021 medical

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Gosselies, Belgium, 12 October 2021, 7:00 am CEST BONE THERAPEUTICS (Euronext Brussels and Paris: BOTHE), the cell therapy company addressing unmet medical needs in orthopedics and other diseases, today announces it has appointed key experts to a Scientific Advisory Board (SAB).

Bone Therapeutics has appointed the members of this SAB specifically to provide additional expert guidance on the development of Bone Therapeutics novel, next generation induced pluripotent stem cell-derived mesenchymal stromal cell (iMSC) platform. This iMSC platform will be used to develop cell and gene therapy products that have strong anti-inflammatory and immunomodulatory properties, for the treatment of acute life-threatening unmet medical diseases.

Bone Therapeutics has appointed its SAB with world-recognized scientists and clinicians in the cell and gene therapy field. Each SAB member has been selected having demonstrated leadership roles in the clinical development of engineered cell and gene therapy for specific acute unmet medical conditions. These specific conditions include graft vs host disease, acute respiratory distress syndrome, sepsis, and trauma, as well as orthopedic conditions including osteoarthritis.

Bone Therapeutics is developing a next generation iMSC platform that has the potential to develop transformative cell and gene therapies for patients suffering from a range of life-threatening unmet medical diseases. Given the therapeutic potential of this platform and to deliver this platform to an operational state as quickly as possible, Bone Therapeutics has brought together a group of world-leading experts to support its development, said Tony Ting, PhD, Chief Scientific Officer, Bone Therapeutics. These thought leaders have been selected to bring a wealth of specific experience in the clinical development of cell and gene therapies. The input from this SAB will be critical as Bone Therapeutics develops its next-generation iMSC products for acute inflammatory diseases.

Given the therapeutic potential of the iMSC platform that Bone Therapeutics is developing, the invitation to chair and help form this scientific advisory board was too tempting to decline, said Massimo Dominici, MD, chair, Bone Therapeutics Scientific Advisory Board. The blend in expertise of this scientific advisory board will be able to provide key advice and consultancy to Bone Therapeutics and will make key contributions to ensure the development of the iMSC platform to reach patients of acute life-threatening unmet medical diseases as quickly as possible.

The Bone Therapeutics Scientific Advisory Board are as follows:

Massimo Dominici, MD, (Chair) - Full Professor of Medical Oncology and Director of the Division of Medical Oncology and of the Program of Cellular Therapy and Immuno-oncology at the University Hospital of Modena and Reggio Emilia (Italy). Also a member of the World Health Organization (WHO) Expert Advisory Panel on The International Pharmacopoeia and Pharmaceutical Preparations serving the INN Expert Group. Since 2016, the Director of the Residency School in Medical Oncology, since 2005, head of the Laboratory of Cellular Therapies at the University Hospital of Modena and Reggio Emilia (Italy). Scientific founder of the university start-up Rigenerand since 2009. Co-founder and coordinator of the Mirandola Science & Technology Park. Co-founder of the Forum of Italian Researcher on MSC (FIRST), board member of JACIE, WBMT and scientific advisor for the Italian Minister of Health. President of ISCT 2014-2016, Emeritus Member of ISCT and now Member of the ISCT Strategic Advisory Council. From June 2014 until May 2020 Chair of the ISCT Presidential taskforce on unproven cell and gene therapies.

Frank Barry, PhD, Professor of Cellular Therapy at the Regenerative Medicine Institute (REMEDI), National University of Ireland Galway and Visiting Scientist at the Schroeder Arthritis Institute in Toronto. He has made key contributions to the fields of tissue engineering and regenerative medicine by developing innovative and successful cellular therapies for tissue repair, joint injury and arthritic disease. By undertaking a large body of basic and translational research, he has contributed to the industrys current understanding of the phenotypic attributes of mesenchymal stromal cells that make them attractive candidates for advanced therapeutics. He has also contributed to the development of methods for automated, efficient and scalable cell expansion for GMP application and has been a leader in the development of clinical protocols for patient testing. He is the Coordinator of the ADIPOA2 clinical trial to test the efficacy of stromal cell delivery as a treatment for osteoarthritis. Frank Barry has received the Marshall Urist Award for excellence in tissue regeneration research from the Orthopaedic Research Society. Recently elected as a Member of the Royal Irish Academy.

Robert Deans, PhD, CSO at Synthego, a genome engineering company automating a new era of cell and gene therapeutics. Previously CTO at BlueRock Therapeutics, creating iPSC based allogeneic cell therapeutics by harnessing pluripotent stem cell biology and gene editing tools and founding CSO at Rubius Therapeutics, developing a platform of novel enucleated cell therapeutics based on genetic engineering and expansion of hematopoietic progenitors to mature red cells. Dr. Deans has more than 30 years of experience in adult stem cell therapeutics which includes HSC gene therapy and commercialization of progenitor cell therapeutics from bone marrow. Richard Maziarz, MD, has been involved in clinical investigation and translational research, for over 30 years, beginning with research and clinical training at the Dana-Farber Cancer Institute and the Brigham & Womens Hospital and continuing in 1991 when he moved to Oregon Health & Science University (OHSU) to develop a transplantation immunology program and served as the medical director of the adult OHSU stem cell transplant program since 1994. His research involved the immunology of transplantation or its complications, particularly in studying the immunopathophysiology of GVHD. He has served as principal investigator or co-investigator on over 100 clinical trials including multiple initiatives sponsored by numerous national transplant organizations including SWOG, CIBMTR, ISCT, NMDP and BMT CTN. Within the BMT CTN, he serves on the Steering committee, chaired the Regimen Related Toxicity Committee, was a member of the GVHD Committee and served as the principal investigator for the BMT CTN on the first multicenter, stem cell transplant trial for patients with advanced chronic lymphocytic leukemia (BMT CTN 0804).

Patricia Rocco, MD, PhD, Full Professor at the Federal University of Rio de Janeiro, and heads the Laboratory of Pulmonary Investigation. Elected Member of the National Academy of Medicine in Brazil and Brazilian Academy of Science. Past Vice-President of ISCT for the South and Central America regions. Authored and co-authored more than 380 peer-reviewed publications and 120 book chapters. She is the President of the Brazilian Society of Physiology (2021-2022). Her research activities focus mainly on the development of new therapies for lung diseases.

About Bone Therapeutics

Bone Therapeutics is a leading biotech company focused on the development of innovative products to address high unmet needs in orthopedics and other diseases. The Company has a diversified portfolio of cell therapies at different stages ranging from pre-clinical programs in immunomodulation to mid stage clinical development for orthopedic conditions, targeting markets with large unmet medical needs and limited innovation.

Bone Therapeutics core technology is based on its cutting-edge allogeneic cell and gene therapy platform with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) which can be stored at the point of use in the hospital. Currently in pre-clinical development, BT-20, the most recent product candidate from this technology, targets inflammatory conditions, while the leading investigational medicinal product, ALLOB, represents a unique, proprietary approach to bone regeneration, which turns undifferentiated stromal cells from healthy donors into bone-forming cells. These cells are produced via the Bone Therapeutics scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, the Company has initiated patient recruitment for the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB continues to be evaluated for other orthopedic indications including spinal fusion, osteotomy, maxillofacial and dental.

Bone Therapeutics cell therapy products are manufactured to the highest GMP (Good Manufacturing Practices) standards and are protected by a broad IP (Intellectual Property) portfolio covering ten patent families as well as knowhow. The Company is based in the BioPark in Gosselies, Belgium. Further information is available at http://www.bonetherapeutics.com.

For further information, please contact:

Bone Therapeutics SAMiguel Forte, MD, PhD, Chief Executive OfficerLieve Creten, Chief Financial Officer ad interimTel: +32 (0)71 12 10 00investorrelations@bonetherapeutics.com

For Belgian Media and Investor Enquiries:BepublicCatherine HaquenneTel: +32 (0)497 75 63 56catherine@bepublic.be

International Media Enquiries:Image Box CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency

For French Media and Investor Enquiries:NewCap Investor Relations & Financial CommunicationsPierre Laurent, Louis-Victor Delouvrier and Arthur RouillTel: +33 (0)1 44 71 94 94bone@newcap.eu

Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such persons officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

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Bone Therapeutics appoints Scientific Advisory Board for iMSC cell and gene therapy platform development - StreetInsider.com

Cell Biology

USF invention addresses worldwide mask shortage and pollution concerns – University of South Florida

October 12, 2021 medical

Technology created at the University of South Florida (USF) could be the key to safely reusing disposable face masks. Researchers have figured out a way to rapidly disinfect and electrostatically recharge N95 respirators, recovering their original filtration efficiency and protection capability against COVID-19 and other airborne diseases.

In their study published in Environmental Science & Technology, the team demonstrated their patent-pending sterilization technology could restore an N95 respirators original filtration efficiency of about 95 percent, even after 15 cycles of treatment. The technology fights coronavirus by using corona discharge ambient atmospheric pressure plasma. The technology works by simultaneously deactivating pathogens on a mask and restoring its electrostatic charges. It is non-thermal, meaning it doesnt require extra heating, and doesnt require chemicals or contact, making it safe and convenient to use. Its reusable, safer than ultraviolet (UV) radiation and is a low-power consumption technique only requiring 1.25 watts of electricity.

In addition to providing protection, corona discharge treatment can have a significant impact on the environment. According to a report released by the Hong Kong-based marine conservation organization OceansAsia, 1.56 billion face masks polluted the oceans in 2020 and will likely take more than 450 years to fully decompose. Instead of individuals using hundreds of masks per year, researchers say the technology will limit their consumption to dozens each year.

It is a reduction of 90 percent for each user. If we assume that 10 percent of the population all over the world takes advantage of corona discharge mask reuse technology, there will be four- five billion fewer masks disposed to the environment, said project lead Ying Zhong, assistant professor in the USF Department of Mechanical Engineering. It will reduce at least 24 million tons of plastic pollution and reduce the amount of chemicals used for mask disinfection and avoid their environmental impact.

Despite the challenging conditions of the pandemic, this was the most thrilling project that I have ever worked on. We wish our research advances the understanding of how corona discharge disinfection can be turned into products on the market as soon as possible, said co-project lead Libin Ye, assistant professor in the USF Department of Cell Biology, Molecular Biology and Microbiology.

The researchers are collaborating with a medical device design company to turn their prototypes into products available to hospitals and to the general public. The team is also working to develop handheld surface screening devices to sterilize homes, hospitals and other public areas, such as restaurants, schools and public transportation.

The technology is funded in part by a $167,568 RAPID grant from the National Science Foundation and a COVID-19 Rapid Response Research Grant from the USF Office of Research and Innovation.

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USF invention addresses worldwide mask shortage and pollution concerns - University of South Florida

Cell Biology

Building the World’s First University Cloud Lab – Technology Networks

October 12, 2021 medical

Carnegie Mellon University (CMU) and Emerald Cloud Lab (ECL) recently announced their plans to build a cloud lab at the university's campus in Pittsburgh. A carbon copy of ECLs lab in San Francisco, the CMU Cloud Lab will enable scientists to perform experiments remotely and give them access to nearly 200 types of scientific instruments.To learn more about the CMU Cloud Lab, the motivation behind the project and the benefits it will bring, Technology Networks spoke to Rebecca Doerge, PhD, dean, Mellon College of Science, Carnegie Mellon University, and Toby Blackburn, head of business development and research, Emerald Cloud Lab.Anna MacDonald (AM): What was the motivation behind creating a cloud lab at CMU?Rebecca Doerge (RD): Carnegie Mellon University excels in the foundational sciences, robotics, machine learning and data science all fields that are at the core of the cloud lab and automated science. Were also in the midst of a future of science initiative, where we are devoting our time and resources to creating the future of science and educating the scientists of the future. It just made sense that we should be the ones to create the worlds first cloud lab at a university.AM: This will be the first cloud lab in an academic setting. Why do you think other universities have so far not adopted this approach?RD: CMU is being visionary and forward thinking in bringing a cloud lab to campus. ECLs Brian Frezza and DJ Kleinbaum are our alumni and they presented us with the chance to be a pioneer in this space. To us, the promise of the cloud lab for academic research and education was undeniable, and we jumped on it early.AM: What makes CMU well suited to host a cloud lab?RD: Carnegie Mellon has long been a world leader in the foundational sciences, computer science, robotics, machine learning and data science, all of which are at the foundation of the cloud lab. Were also known for being an institution where interdisciplinary collaboration is encouraged and thrives. Scientists at Carnegie Mellon often collaborate with computer scientists, engineers and statisticians to enhance their work using technology. The cloud lab is an extension of this.Carnegie Mellon is also committed to educating the next generation of scientists. Part of that is preparing them to use the latest methods and technologies. Giving our students access to a cloud lab will expose them to coding and automated science. It will also provide CMU students with greater access to state-of-the-art research equipment when they conduct their own research.

AM: Can you tell us more about the platform that the lab will be based on?Toby Blackburn (TB): Emerald Cloud Lab is the worlds first state-of-the-art pre-clinical biopharma R&D laboratory that runs experiments virtually from the cloud. Experiments ranging from basic chemistry to cell biology can be run using ECLs collection of instruments that encompass 190 different capabilities, all through one single platform, ECL Command Center.The Carnegie Mellon University Cloud Lab will be based on ECLs Global Cloud, a facility located in South San Francisco that is accessible to enterprise, start-up and academic customers. Command Center, the system used to interact with the lab and data, will function in the same way across both facilities, allowing for interoperability of experiment commands and data analysis functions.AM: Can you give us an overview of how the cloud lab will work? What equipment will be available and what experiments will be possible?TB: The cloud lab will work identically to the current ECLs Global Cloud but will be wholly dedicated to the experiments and research of the CMU community.Scientists will use Command Center to design their experiments, which are then performed in the Cloud Lab. Once an experiment is complete, users can also perform all data analysis, visualization and interpretation within Command Center.Equipment and capabilities of the CMU Cloud Lab are largely based on the ECL Global Cloud, but we are presently working with CMU to finalize the list of equipment and ensure that the facility will meet the needs of CMU faculty, staff and students.AM: In what ways do you expect the cloud lab to benefit faculty, students and the wider community?RD: The Carnegie Mellon University Cloud Lab will democratize science. Carnegie Mellon faculty and students, both undergraduate and graduate, will no longer be limited by the cost, availability and location of equipment. We also plan to open the Carnegie Mellon Cloud Lab to others in the research community, including high school students, researchers from smaller universities that may not have advanced research facilities and local life sciences startup companies.AM: How does developing and implementing a cloud lab in an academic setting compare to developing one in an industry setting?TB: Functionally, both Cloud Labs will work the same way, with the CMU facility leveraging all of the development and lessons learned from building the ECL. We plan to maintain this compatibility, allowing CMU to benefit from the further development arising from our pharma and biotech clients, and vice versa.One thing we are really excited about is the public nature of academic research. With the potential for research to be published with not only the raw data associated with the research, but also the experimental commands used to generate that raw data at the push of a button, the cloud lab can really change the landscape of scientific research and go a long way to address the reproducibility crisis.AM: Do you have any advice for other academic institutions thinking of developing a cloud lab?TB: Universities should be constantly looking for new and better ways to do research and provide education. A cloud lab is a great example. Over the last few years Carnegie Mellon faculty has used ECLs facilities for research and education. On the research front, weve found that using the cloud lab accelerates the pace of discovery and yields accurate, replicable and sharable data. On the education front, students are excited about the cloud lab. We believe that the cloud lab is part of the future of science and believe that it is important for academic institutions to begin to use the platform.

Additionally, having access to ECL facilities was a game-changer while many of us were working and learning remotely due to COVID-19. We were able to use the cloud lab to give students who were learning remotely a laboratory experience. And while many researchers had to pause their laboratory work, those who were working with the cloud lab could continue to do experiments.Rebecca Doerge and Toby Blackburn were speaking to Anna MacDonald, Science Writer for Technology Networks.

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Building the World's First University Cloud Lab - Technology Networks

Cell Biology

Innovative Experiment Reveals the Complex Dynamics of Stem Cell Tethers and Slings – SciTechDaily

October 12, 2021 medical

Research conducted at KAUST aims to improve how stem cells move in the body so that they can reach where they are needed following transplantation. Credit: 2021 KAUST; Anastasia Serin

Molecules move within elongated protrusions to help stabilize migrating cells inside the bloodstream.

An innovative experiment design shows, in real time and at the scale of a single molecule, how stem cells slow their rolling inside the circulatory system by growing long tethers that attach to the inner surfaces of blood vessels. The strategy could help researchers to improve stem cell transplantations and to find new treatments for metastasizing cancers.

Many cells in the human body travel through blood vessels from one organ to another to carry out specific functions. For example, immune cells migrate to inflamed tissue and cancer cells spread to new organs. Stem cells also travel to new locations to develop into different tissues. This stem cell homing, where cells migrate to their new place of residence, is also essential for successful bone marrow transplantation for treating various diseases, explains Satoshi Habuchi, who led the study.

Homing is a multistep process in which cells slowly roll over the inner lining of blood vessels, then adhere to the lining once they reach the site they are destined for, and finally transmigrate across the vessel wall into the tissue.

Scientists already knew that homing cells produce tethers containing ligands that can sense and bind to adhesion molecules on the blood vessel lining. Until now, however, scientists had not been able to directly visualize this rolling to understand exactly what happens at the molecular level.

Stem cell homing is a process whereby stem cells migrate through the circulatory system to arrive at the place where they are required in the human body. Credit: 2021 KAUST; Anastasia Serin

Satoshi, Merzaban and their teams were able to mimic cell rolling by using a microfluidic system. The tethering and rolling step of homing had previously been described as a simple binding between selectins on the endothelium and their ligands on stem cells, says Ph.D. student Bader Al Alwan. Our findings demonstrated that the initial step of homing is far more dynamic and complicated.

Part of the teams research is focused on understanding why cancer cancer cells outperform normal cells in their ability to migrate around the human body. Credit: 2021 KAUST; Anastasia Serin

The team found that individual microvilli on the surface of the homing cells elongate to form individual tethers. Ligands in the microvilli rapidly extend throughout the tethers so they can sniff out selectin in the blood-vessel lining. Once located, the ligands bind to the selectins, attaching the tether to the vessel lining. This helps the cell resist the full strength of the blood flow. As the blood flow exerts pressure on the top of the cell, it rolls forward, stretching the tether until it reaches a critical point when it breaks and flips forward to come in front of the cell. Now called a sling, it is used to slow down the cell so that it can look for the molecules that signal where its new home is.

When we started, we did not expect that cell morphology played such a critical role in stabilizing cell rolling, says Al Alwan. We were also surprised by the extent to which the morphology changes, with some tethers merging into multiple ones and others stretching to more than ten times the length of the cell.

The team, led by Satoshi (right), want to create a more precise map of the proteins that are present at each step of the homing and migration process. Credit: 2021 KAUST; Anastasia Serin

Our research is focused on understanding how various cells move in the body using adhesion systems. For example, one goal is to improve stem cell movement in the body so they can get where they are needed following transplantation or in other disease settings. We are also focused on understanding how and why cancer cells outperform normal cells in their ability to migrate so that we can develop methods to inhibit their metastasis. Using the sophisticated assays developed by Satoshi and his team, we also want to create a more precise map of the proteins that are present at each step of the homing and migration process to identify when and where they are important during migration, says bioscientist Jasmeen Merzaban, the co-principal investigator of the study.

Reference: Single-molecule imaging and microfluidic platform reveal molecular mechanisms of leukemic cell rolling by Bader Al Alwan, Karmen AbuZineh, Shuho Nozue, Aigerim Rakhmatulina, Mansour Aldehaiman, Asma S. Al-Amoodi, Maged F. Serag, Fajr A. Aleisa, Jasmeen S. Merzaban and Satoshi Habuchi, 14 July 2021, Communications Biology.DOI: 10.1038/s42003-021-02398-2

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Innovative Experiment Reveals the Complex Dynamics of Stem Cell Tethers and Slings - SciTechDaily

Cell Biology

Lung Cancer Treatment Response Linked to Cancer-Associated Fibroblast Cell Subtypes – GenomeWeb

October 12, 2021 medical

NEW YORK A team from the Massachusetts General Hospital, Novartis Institutes for BioMedical Research, and elsewhere has identified a handful of lung cancer-associated fibroblast subtypes with distinct clinical or biological features, including responses to tyrosine kinase inhibitor treatments.

"[W]e identify three major functional subtypes of [cancer-associated fibroblast (CAF)] that exhibit distinct impacts on treatments using EGFR and ALK TKIs," first author Haichuan Hu, an instructor in medicine with the MGH Cancer Center and Harvard Medical School, and his colleagues wrote in a study published in Cancer Cell on Thursday.

In the process, the team put together a CAF biobank that included samples from NSCLC cases with EGFR mutations or ALK fusions, offering clues to the fibroblast cell features that were shared and distinct in relation to the tumor cells.

"This large collection of CAFs allows us to adequately recapitulate a broad spectrum of NSCLC CAFs with diverse molecular features," the authors explained. "Here, we functionally characterize the landscape of NSCLC CAFs, reveal how they function differently, and demonstrate their potential clinical utilities."

For their analyses, the investigators first generated dozens of patient-derived fibroblast cultures using CAF cells isolated from non-small cell lung cancer biopsy samples. From there, they relied on a range of experiments including RNA sequencing, RT-qPCR, immune, and secretome assays; and phenotypic, functional, mouse model, and targeted treatment response profiling along with available single-cell and bulk RNA sequence data on NSCLC-associated fibroblasts to define three CAF subtypes with distinct biological and clinical characteristics.

In an email, Hu noted that such analyses may ultimately lead to personalized lung cancer treatment plans that take all the cell types in a lung tumor, including CAFs, into account.

"[W]e are able to demonstrate a link between an NSCLC patient's clinical response and the functional classification of CAFs from that patient's tumors," he and his co-authors wrote, "thus providing evidence supporting that this CAFs functional classification may have considerable value in future clinical management of cancer patients."

In the cluster of CAFs from subtype I, for example, the team saw higher-than-usual levels of hepatocyte growth factor (HGF) and fibroblast growth factor 7 (FGF7), along with protection of corresponding cancer cells against TKI treatment. Subtype II CAFs were also marked by enhanced FGF7 expression, but showed more moderate cancer protection than subtype I.

In those two subtypes, the researchers noted, combination treatments that include HGF-MET and/or FGFR pathway targeting may be effective, based on the new CAF data. On the other hand, CAFs in subtype III were linked to immune cell migration and tended to turn up in NSCLC patients with more promising clinical outcomes, hinting that immune-focused treatments may have promise in cases with these HGF-low, FGF7-low, and higher phospho-SMAD2 levels, which correspond to TGF-beta signaling.

"Apart from targeted therapy, we show that this CAF classification also has potential for evaluating patients in the context of immune therapy and may also aid in the research in other aspects of cancer biology," the authors wrote, adding that "[o]ur approach in exploring and exploiting fibroblast heterogeneity may also provide a valuable paradigm for these disciplines to further improve clinical patient management."

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Lung Cancer Treatment Response Linked to Cancer-Associated Fibroblast Cell Subtypes - GenomeWeb

Cell Biology

Scientists assemble a biological clock in a test tube to study how it works – Newswise

October 12, 2021 medical

Newswise Daily cycles in virtually every aspect of our physiology are driven by biological clocks (also called circadian clocks) in our cells. The cyclical interactions of clock proteins keep the biological rhythms of life in tune with the daily cycle of night and day, and this happens not only in humans and other complex animals but even in simple, single-celled organisms such as cyanobacteria.

A team of scientists has now reconstituted the circadian clock of cyanobacteria in a test tube, enabling them to study rhythmic interactions of the clock proteins in real time and understand how these interactions enable the clock to exert control over gene expression. Researchers in three labs at UC Santa Cruz, UC Merced, and UC San Diego collaborated on the study,published October 8 inScience.

Reconstituting a complicated biological process like the circadian clock from the ground up has really helped us learn how the clock proteins work together and will enable a much deeper understanding of circadian rhythms, said Carrie Partch, professor of chemistry and biochemistry at UC Santa Cruz and a corresponding author of the study.

Partch noted that the molecular details of circadian clocks are remarkably similar from cyanobacteria to humans. Having a functioning clock that can be studied in the test tube (in vitro) instead of in living cells (in vivo) provides a powerful platform for exploring the clocks mechanisms and how it responds to changes. The team conducted experiments in living cells to confirm that their in vitro results are consistent with the way the clock operates in live cyanobacteria.

These results were so surprising because it is common to have results in vitro that are somewhat inconsistent with what is observed in vivo. The interior of live cells is highly complex, in stark contrast to the much simpler conditions in vitro, said Andy LiWang, professor of chemistry and biochemistry at UC Merced and a corresponding author of the paper.

The new study builds on previous work by Japanese researchers, who in 2005 reconstituted the cyanobacterial circadian oscillator, the basic 24-hour timekeeping loop of the clock. The oscillator consists of three related proteins: KaiA, KaiB, and KaiC. In living cells, signals from the oscillator are transmitted through other proteins to control the expression of genes in a circadian cycle.

The new in vitro clock includes, in addition to the oscillator proteins, two kinase proteins (SasA and CikA), whose activities are modified by interacting with the oscillator, as well as a DNA-binding protein (RpaA) and its DNA target.

SasA and CikA respectively activate and deactivate RpaA such that it rhythmically binds and unbinds DNA, LiWang explained. In cyanobacteria, this rhythmic binding and unbinding at over 100 different sites in their genome activates and deactivates the expression of numerous genes important to health and survival.

Using fluorescent labeling techniques, the researchers were able to track the interactions between all of these clock components as the whole system oscillates with a circadian rhythm for many days and even weeks. This system enabled the team to determine how SasA and CikA enhance the robustness of the oscillator, keeping it ticking under conditions in which the KaiABC proteins by themselves would stop oscillating.

The researchers also used the in vitro system to explore the genetic origins of clock disruption in an arrhythmic strain of cyanobacteria. They identified a single mutation in the gene for RpaA that reduces the proteins DNA-binding efficiency.

A single amino acid change in the transcription factor makes the cell lose the rhythm of gene expression, even though its clock is intact, said coauthor Susan Golden, director of the Center for Circadian Biology at UC San Diego, of which Partch and LiWang are also members.

The real beauty of this project is how the team drawn from three UC campuses came together to pool approaches toward answering how a cell can tell time, she added. The active collaboration extended well beyond the principal investigators, with the students and postdocs who were trained in different disciplines conferring among themselves to share genetics, structural biology, and biophysical data, explaining to one another the significance of their findings. The cross-discipline communication was as important to the success of the project as the impressive skills of the researchers.

The authors of the paper include first authors Archana Chavan and Joel Heisler at UC Merced and Jeffrey Swan at UC Santa Cruz, as well as coauthors Cigdem Sancar, Dustin Ernst, and Mingxu Fang at UC San Diego, and Joseph Palacios, Rebecca Spangler, Clive Bagshaw, Sarvind Tripathi, and Priya Crosby at UC Santa Cruz. This work was supported by the National Institutes of Health and the National Science Foundation.

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Scientists assemble a biological clock in a test tube to study how it works - Newswise

Cell Biology

AgTech NEXT 2021 Concludes with a Focus on the Impact of Climate Change on Food Security – Newswise

October 12, 2021 medical

Newswise ST. LOUIS, MO, October 11, 2021 - Climate changes are occurring in every region of the world according to the recent UN report. The developing world has been disproportionately impacted and the effects of a changing climate are creating greater food and water insecurity and economic instability. With this in mind, AgTech NEXT 2021 CLIMATE CHANGE: Seeing Things Differently, will continue on November 18, at 1PM CST featuring a keynote address by Joe Cornelius, PhD, CEO, Gates Ag One, followed by a panel discussion with leaders of organizations working to advance new technologies to ensure food security in sub-Saharan Africa and South Asia. AgTech NEXT is complimentary to attend. To register, please visit agtechnext.org/register.

As CEO of Bill & Melinda Gates Agricultural Innovations (also known as Gates Ag One), Cornelius guides the organizations efforts to champion innovations and cultivate global networks that prioritize the needs of smallholder farmers.Cornelius began his career on a small, diversified family farm and has dedicated his professional life to improving the world through agricultural advancements. Most recently, he led efforts to strengthen agricultures adaptive capacity to climate change at the Bill & Melinda Gates Foundation, where he served as a director for its Global Growth and Opportunity Division. Cornelius has more than 30 years experience developing and launching new product inventions and has led breakthrough life-science research at multiple organizations including the Advanced Research Projects Agency in the U.S. Department of Energy. He holds a Ph.D. and M.Sci. in plant, soil and environmental science, as well as an MBA in technology entrepreneurship.

The people most at risk from the consequences of climate change are those in the least developed parts of the world. Thats why the priorities of smallholder famers in regions like sub-Saharan Africa and South Asia need to be at the top of our agenda, shared Dr. Cornelius. Its only when we understand and focus on their priorities that we can develop the tools needed for the world to effectively adapt.

Limiting the negative impact of climate change requires bold and creative action coupled with focused and sustained collaboration, especially in regions of the world that are most at risk, said Stephanie Regagnon, Executive Director, Innovation Partnerships at the Donald Danforth Plant Science Center. Gates Ag Ones presence in St. Louis amplifies the impact the Danforth Center and our local collaborators can have to address these urgent challenges.

NOVEMBER 18, 2021 - St. Louis, MO1:00-2:00 PM AGRICULTURE INNOVATION FOR CLIMATE ADAPTATION AND RESILIENCE

KEYNOTE: Joe Cornelius, PhD, CEO, Bill & Melinda Gates Agricultural Innovations, LLC

PANEL SESSION COLLABORATION AND CO-DEVELOPMENT FOR SUSTAINED IMPACTDr. Rose Gidado, PhD, Deputy Director, National Biotechnology Development Agency & Country Coordinator, Open Forum on Agriculture Biotechnology in Africa, Nigeria ChapterDr. Catherine Taracha, PhD, Head, Crop Biotechnology at the Kenya Agricultural and Livestock Research OrganizationDr. Pooja Bhatnagar-Mathur, PhD, Theme Leader-Cell, Molecular Biology and Genetic Engineering at the International Crops Research Institute for the Semi-arid Tropics in Hyderabad, India and Cluster of Activities Leader on Enabling Technologies, CGIAR Research Program on grain Legumes & Dryland CerealsDr. Don MacKenzie, PhD, Executive Director, Institute for International Crop Improvement, Donald Danforth Plant Science CenterMODERATOR: Joseph Opoku Gakpo, Journalist, Joy FM and Joy News TV, Ghana