MARLBOROUGH, Mass. & LOUISVILLE, Ky.--(BUSINESS WIRE)--GE Healthcare Life Sciences and Advanced Solutions Life Sciences (ASLS) will enter into a strategic R&D and distribution partnership that sets out to personalize tissue regeneration. The integration of IN Cell Analyzer and BioAssemblyBot systems technologies will embed cellular-level assessments into the 3D-bioprinting workflow used to create human tissue models.

Bioprinted tissues are small in size and die quickly, due to an inability to engineer small blood vessels the bodys supply network. ASLS patented Angiomics technology enables bioprinted microvessels to self-assemble into functional capillary beds, which deliver nutrients, oxygen, and hormones to the 3D tissue model and remove waste. This partnership would allow life scientists and tissue engineers to quickly design, build and image living, vascularized 3D tissues in a single, agile process.

Emmanuel Abate, General Manager of Genomics & Cellular Research, GE Healthcare Life Sciences, says: Printing multi-material 3D objects inside of microwell plates allows scientists to efficiently move away from traditional 2D monocultures on plastic, to 3D discovery and cytotoxicity models that more accurately reflect native biology and disease. By combining this flexibility and precision of the BioAssemblyBot with the image quality and speed of the IN Cell Analyzer 6500 HS confocal screening platform, the prospect of automating high content screening in 3D models can become a reality.

Currently, biopharmaceutical companies test their drugs in 2D models and animal models. Precise 3D models provide a more physiologically relevant environment for drug testing because they mimic human reactions.

The power of both of these platforms brings a new level of efficiency, speed and quality with assay designs and 3D biofabrication, says Michael Golway, President & CEO of ASLS.

Traditional 3D bioprinters are not designed for quality or interoperability with the high-throughput screening methods that pharmaceutical developers use to identify drug candidates. This alliance will result in a new product to address this challenge: an integration of GE Healthcare Life Sciences IN Cell Analyzer confocal imaging platform with IN Carta cell analysis software, and ASLS BioAssemblyBot 3D bioprinter with TSIM design software.

For pharmaceutical companies, where the average time to develop a new drug candidate may take over seven years, moving from traditional stage-gate testing processes to a lean, agile workcell for 3D tissue fabrication and assessments will shorten development timelines. The integration between IN Cell Analyzer and BioAssemblyBot enables the automated inclusion of cellular imaging information into the tissue modeling process so that new therapies can be scaled more quickly and effectively.

To learn more, please go to http://www.lifesciences.solutions/GE

For a live demonstration visit booth #908 at the joint meeting of the American Society of American Cell Biology (ASCB) and the European Molecular Biology Organization in Washington, DC taking place from December 7-11, 2019.

About GE Healthcare Life Sciences:

GE Healthcare Life Sciences helps therapy innovators, researchers and healthcare providers accelerate how precision diagnostics and therapies are invented, made and used. Our products enable biological analysis, research, development and the manufacture of advanced therapies and vaccines. Life Sciences is part of the $19.8 billion healthcare business of GE (NYSE: GE). With over 100 years of experience in the healthcare industry and more than 50,000 employees globally, GE Healthcare helps efficiently improve outcomes for patients, healthcare providers, researchers, and life sciences companies around the world. Visit our website https://www.gelifesciences.com/about-us for more information.

About Advanced Solutions Life Sciences:

Advanced Solutions Life Sciences (ASLS) is dedicated to the discovery, design, and development of integrated software and hardware solutions for the fields of science that involve living organisms, molecular biology, and biotechnology. ASLS offers a full-service business model including its patented, cGMP and UL certified BioAssemblyBot platform, as well as BioBot Basic, TSIM and BioApps Software, VIPM, and Professional Services. Visit http://www.bioassemblybot.com for more information.

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GE Healthcare Life Sciences pairs up with Advanced Solutions Life Sciences to create new opportunities for regenerative tissue manufacturing -...

It could be that malaria-carrying parasites are rendered less potent by minestrone. hmproudlove/Getty Images hide caption

It could be that malaria-carrying parasites are rendered less potent by minestrone.

Bring in some soup.

The unusual homework assignment at London's Eden Primary School was for a science week project cooked up by parent Jake Baum. He's a professor of cell biology and infectious diseases at Imperial College London, and his lab's job is to find new ways to combat malaria, which kills half a million children each year.

Baum figured he could teach young students about the process of medical research through something both tasty and understandable: the go-to soup recipes their families use when someone gets sick.

"What makes a good medicine versus hocus-pocus?" explains Baum, who regularly preps his own favorite home remedy, something he calls "Jewish grandmother's chicken soup."

"It was not the plan to discover anything," he adds.

Sixty students transported their soup submissions to school in 15 milliliter plastic tubes. That's about 1 tablespoon. The soup was frozen, thawed (standard practice for samples) and then (much to the children's delight) centrifuged spun in a machine to separate different substances.

At the next step, filtration, four samples were determined to be too dense or oily to test. Although they were likely delicious, they didn't make it to the lab stage, where the remaining 56 samples were tested in two ways against the P. falciparum parasite the species responsible for 99% of malaria deaths.

First, researchers checked what effect the soups had on asexual growth during the disease-causing stage. Or, to put it in primary school terms, they were looking through the microscope for the color green.

"More green means [the parasites are] happy. With an inhibitor like a drug, it's less green," Baum says. They followed up by checking on male parasite sexual development, which is responsible for disease transmission. For that, they recorded the movement of the parasites because, as Baum notes, "sperm wiggle."

To Baum's surprise, with five of the soups, the color green was much dimmer five of them were able to suppress growth by over 50% (and two of these even did about as well as a leading antimalarial, dihydroartemisinin).

In other soups, there was a lot less wiggling. Four were found to have blocked transmission activity by more than 50%.

"We just said, 'Wow, what do we do with this?' " Baum says.

The answer turned out to be another teachable moment for the students, ages 4 to 11, who participated in the study. Although the results were collected within a few months, it took two years for the work to get published. Another Eden Primary parent, pediatric nephrologist Stephen Marks, helped pitch the study to journals and championed the idea that the children of the school should be listed as authors which they were when the study was finally released in November in the Archives of Disease in Childhood.

"Every kid can say they've had their first scientific paper," says Baum, who jokes that some may want to turn it into a paper airplane.

But it was a project they're likely to remember, notes Susanna Daniels, another parent/scientist, who also happens to be a soup enthusiast. As soon as her two children in the school came home to tell her about the experiment, there was some hypothesizing going on. "Our oldest was most disappointed because I'm a pescatarian. She was anxious our soup would fail because it wasn't chicken soup," explains Daniels, who opted to make her mother's veggie minestrone, loaded with cabbage, carrots, celery and tomato.

Turns out, that combo did especially well in the study, accounting for two of the samples that helped block transmission activity. "It wasn't a fluke finding because it was duplicated in both samples," Daniels says. The kids were thrilled to get the news, she adds. "They wanted to ring my mum straight away. She was quite bemused by the whole thing."

It's not so far-fetched to search for medical breakthroughs in your grandma's or great uncle's kitchen concoctions, Baum says, pointing to the scientific literature extolling the curative properties of chicken soup. (Research studies like this one suggest that it curbs some symptoms of upper respiratory tract infections.)

In terms of malaria treatment, the original lifesaving medicine was quinine, found in the bark of the South American cinchona tree. Today, the most commonly recommended anti-malaria drugs are derived from the artemesia plant (aka wormwood), which has been prescribed in traditional Chinese medicine for over 1,000 years. As Baum says, "Nature can produce fantastic molecules."

Pinpointing what exactly it was about these specific soups that had an effect would take years of additional research. For starters, it's hard to even tell what was in them. A bright red one probably contained beets, and a lot of them smelled like chicken. But students were never asked for a list of ingredients. Even though some kids had written information on the plastic tube samples they submitted, "when we wiped the tubes with ethanol, we lost the recipes," Baum says.

No one is claiming that these soups offer a promising pathway to a cure. "I'm using a lot of 'could, would, possibly,' " notes Baum, who doesn't have current plans for more soup experiments. But if he did and the resources were available he'd love to see it performed globally. Although the Eden Primary students come from diverse ethnic backgrounds, Baum says, they're all doing their grocery shopping in London. They can't pluck a leaf from a particular kind of bush the way kids in other parts of the world might.

Building on local knowledge is vital in malaria research, agrees Stephanie Yanow, a global health professor at the University of Alberta, who was not involved in the soup study. "We're at a difficult point every intervention we've tried, the parasite is always ahead of the game. Malaria numbers are going up in some places. There's drug resistance. The vaccine we have isn't very effective," she says. "We need to think outside the box and use more unconventional methods."

What struck her about the project was how well it engaged kids and their families and encourages "citizen scientists," or people without formal scientific training, to get involved in research.

And it's definitely made Yanow wonder what mysteries await in her minestrone. "There's a reason we think of it as a comfort food," she says.

Vicky Hallett is a freelance writer who regularly contributes to NPR.

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Malaria-Transmitting Parasites Seem To Be Hampered By Minestrone And Other Soups : Goats and Soda - NPR

DetailsCategory: AntibodiesPublished on Monday, 09 December 2019 18:35Hits: 253

CAMBRIDGE, MA, USA I December 09, 2019 IMagenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology (ASH). These results, which were highlighted in an oral presentation at ASH by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate (ADC), without the use of chemotherapy or radiation.

Todays conditioning regimens involve high doses of chemotherapy, often paired with radiation, to remove the disease-causing cells. As a result, patients undergoing gene therapy or stem cell transplant are all faced with a difficult choice: whether to endure severe toxicity and risk infertility and cancer for the chance for a cure. Magentas portfolio of targeted ADCs represents an extremely promising new option to prepare patients for gene therapy or transplant with no need for toxic chemotherapy or radiation, said Dr. Tisdale. The results presented today show that a single dose of single agent CD117-ADC achieves the same level of depletion as four doses of busulfan chemotherapy to enable successful engraftment and persistence of stem cells modified with the -globin gene, the gene that causes sickle cell disease and -thalassemia when mutated. Importantly, the animals undergoing preparation with CD117-ADC showed none of the damaging toxicities associated with busulfan conditioning.

Magenta is the only company with the people, platforms and a product engine committed to comprehensively transforming immune and blood system reset, which includes revolutionizing the toxic methods that are used to prepare patients for gene therapy and transplant today. said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. The gene therapy field has learned that higher levels of stem cell depletion, which meant higher doses of busulfan, were needed to ensure long-term engraftment of the gene-modified cells and persistence of gene therapy. Across all the modalities we have tested, we have seen that ADCs are most effective at achieving these high levels of stem cell depletion without chemotherapy to enable engraftment and long-term durability of the transplant. Todays impressive results provide important validation of the ADC approach as well as the CD117 target for patient preparation and underscore Magentas leadership in the field of conditioning.

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610) Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magentas most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

About Magenta Therapeutics

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

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

SOURCE: Magenta Therapeutics

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Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug...

Chase Beisel heads the "Synthetic Biology of RNA" research group at the Helmholtz Institute for RNA-based Infection Research (HIRI) in Wrzburg, a branch of the Helmholtz Centre for Infection Research (HZI) in Braunschweig and run in collaboration with the Julius-Maximilians-Universitt in Wrzburg. With the Consolidator Grants, the European Research Council (ERC) promotes research by up-and-coming scientists in Europe.

CRISPR is a word on everyone's lips at the moment. Although it sounds somewhat crispy and delicious, it is in fact inedible - it is actually one of the most promising tools of genetic engineering. CRISPR stands for "Clustered Regularly Interspaced Short Palindromic Repeats". These short DNA segments in the genome of bacteria are named after their regular pattern of repeating and mirrored sequences. They act as effective virus defence systems for bacteria. Copies of the CRISPR DNA exist in the form of RNA fragments in the cell. In the event of a viral attack, where a virus injects its DNA into a bacterium, the defence mechanism is triggered: The proteins, which include Cas9, is called to action and compares the sequence of the foreign DNA with that of the CRISPR RNA fragments. If it finds a matching counterpart, Cas9 cuts the foreign virus DNA, thus rendering the intruder harmless. The CRISPR-Cas9 system is therefore also known as genetic scissors and is now used for genome editing. DNA sequences can be specifically cut and modified in the laboratory using custom-designed CRISPR gene scissors, for example for the development of improved crops or medicines, for the manufacture of industrially used microorganisms, and in human cells for treating genetic diseases.

American chemical engineer Chase Beisel dedicated himself to CRISPR research around nine years ago. "We have an incredibly powerful genetic engineering tool at our disposal," says Beisel. "In order to fully and safely utilise its potential in the future, it is important that we better understand the basic biological relationships of CRISPR complexes in bacteria." The bacterial immune system can evidently learn new things and arm itself against other attackers by quickly integrating parts of foreign DNA into its own genome. CRISPR arrays encode the memory of previous infections and enable multiple intruders to be attacked simultaneously. How exactly these advanced CRISPR complexes are created, which criteria are used for selecting new sequences and which key genes of the attacker are thus rendered ineffective are not yet fully understood. This is exactly where Beisel's current research project "CRISPR Combo" aims to start, addressing the unanswered questions. "In addition to researching the biological fundamentals of CRISPR arrays in bacteria, we would also go one step further in the direction of a genetic application of CRISPR arrays," says Beisel. "To do this, we will use designed CRISPR arrays to target multiple genes at once in pathogens, thereby identifying combinations that most drive infections and providing new drug targets."

In 2018, Beisel moved from the Department of Chemical and Biomolecular Engineering at the North Carolina State University in Raleigh (USA) to the HIRI in Wrzburg, where he has been the head of the "RNA Synthetic Biology" research group for two years now. His twelve-person team consists of postdocs, doctoral candidates, technicians and students. "The funding from the ERC means I can confidently add four members to the team - that is really fantastic," says Beisel. "The ERC Grant is an important milestone for me personally. Making the leap to Germany to join the HIRI was absolutely the right decision, and I am delighted about this funding. It enables me to dedicate my research to a topic that fascinates me and at the same time offers significant benefits for society as a whole."

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Bacteria, Cas9, Cell, CRISPR, DNA, Gene, Genes, Genetic, Genetic Engineering, Genome, Genome Editing, Hospital, Immune System, Laboratory, Palindromic Repeats, Research, Research Project, RNA, Virus

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ERC promotes CRISPR research to better treat infections - News-Medical.net

On a daily basis, multitudes of molecules enter each cell in our body. These can be nutrients or signal molecules or pathogenic microorganisms. An organelle in the cell directs these molecules to other stations for further processing. This organelle is called the endosome.

If the pathways by which this sorting occurs fails at any stage, several diseases such as neurodegenerative diseases and certain cancers can occur. Thus, a better understanding of the steps in these pathways is of utmost importance.

In a recent study published in Communications Biology, a group of scientists from Japan and Austria, led by Prof Jiro Toshima from the Tokyo University of Science, reports a new finding regarding the maintenance and functioning of the endosome.

Conventional knowledge is that two processes are necessary for the upkeep of endosomes: a) sacs of molecules constantly form at the cell membrane, are transported to the endosome, and fuse into it; b) protein-containing vesicles transported from the Golgi (another cell organelle) fuse with the endosome.

The researchers of this study claim that this is not the case.

They introduce genetic mutations and drugs into yeast cells to inhibit each of these transport processes at a time.

When transport from the Golgi does not occur, a protein essential to the upkeep of the endosome, Rab5, is not activated, and endosome formation is affected. When cell transport from the membrane is inhibited, there is no effect on the endosome.

Thus, essentially, transport from the Golgi is necessary and that from the cell membrane is dispensable, or not as crucial. "Our results provide a different view of endosome formation and identify the Golgi as critical for the optimal maintenance and functioning of endosomes," Prof Toshima says.

This study clarifies only a fraction of the molecule-sorting pathway in cells. But, this is certainly one giant step in the research in this field. Perhaps, the insights from this study will soon appear on the pages of cell biology textbooks.

Source:

Journal reference:

Nagano, M. et al. (2019) Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. doi.org/10.1038/s42003-019-0670-5.

Link:
New findings regarding maintenance and functioning of the endosome - News-Medical.net

We found that was not helpful to abuse of those. I will have to go through the remaining part of the book to learn. Normally, the quantity of smart transaction boxes is equal to the sum of parties essaysource.com of a signed contract. The very first day was simply wonderful. But sometimes whats more, it checks to see whether its the best time to replicate.

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The accomplishment by a worldwide group of scientists is significant, not merely due to its sheer size, but also due to the insights it may provide into tissue regeneration. Carbon is possibly the most important element for all living organisms. Every one of these techniques has a particular part to play in allowing scientists to study the critical molecules that form the foundation for life. Opt for an associative chain and receive a hash of its very last block.

Cyclin degradation is needed for the cell to leave the M-phase and most likely the inactivation of p34cdc2. They may be used as enzymes to catalyze certain reactions. This makes a phospholipid. Many nutrient molecules are so big and complex they have to be split homework into smaller molecules before they may be employed by the organism.

If chromosomes arent correctly connected to the spindle apparatus, the metaphase checkpoint will halt the cell cycle. Checkpoint regulation has an important part in an organisms development. 1 chromatid from every pair goes to every daughter cell.

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Programs concentrate on the use of contemporary technologies in biological research. Bircham University cannot carry out this evaluation without the comprehensive application for admission. Some students might need to take courses during Summer Session to satisfy these requirements.

And on top of that, its totally free! So that was not a truly huge change for me. However, we have to trust on many other techniques when working in a lab. And hes attracted lots of competitive grants for his research. It could help you save you considerable time and, most significantly, safeguard your undertaking.

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The Benefits of Molecular Cell Biology - Books LIVE

Inside our cells, natural housekeeping processes are going on every day.

Proteins required for basic life processes carry out this work across all cell types in the body.

But they require regulation. Like a parent endlessly clearing up after teenagers to prevent too much mess accumulating, our cells tightly control levels of this activity to maintain smooth operation.

The most common way of achieving this is by turning on or off genes in response to the need for the housekeeping protein products they create.

This is accomplished via feedback control of transcription the first step in the process of gene expression, by which information from a gene is used to create a functional product like a protein.

A second method is to degrade messenger RNA (mRNA), which acts as an intermediate carrying instructions in the process of turning a gene into a protein. By stopping these messages, less protein is made.

It was almost 40 years ago that researchers noticed that cells monitor the amount of a group of housekeeping proteins called tubulins and adjust levels of tubulin mRNAs accordingly.

This is called autoregulation, but no factors in the feedback process have previously been identified until now.

In the Cell Biology Division of the MRC Laboratory of Molecular Biology, Manu Hegdes lab has discovered a protein used by cells to find unnecessary mRNA and trigger its destruction.

This is significant not just for our understanding of cellular processes, but also in the fight against disease.

Tubulins are key to the structure and function of neurons, and mutations in tubulin genes cause various neurodevelopmental diseases. Drugs used to treat gout and certain cancer types also target tubulin.

This means that the discovery of a factor regulating tubulin could help lead to new therapeutics for such diseases.

Zhewang Lin in Manus lab searched for factors that selectively engage our cells protein-making factories ribosomes when producing tubulin. He discovered a factor called TTC5 that binds only ribosomes actively making tubulin.

Working with Vish Chandrasekaran, in Venki Ramakrishnans group within the LMBs Structural Studies Division, the structure of TTC5 when bound to a tubulin-producing ribosome was then determined.

They found a groove, within which the beginning of tubulin binds as it emerges from the ribosome like an item being captured as it comes off a factory production line.

Zhewang then made mutations in TTC5, which made them unable to regulate tubulin production rates when excess was present. The factory, in other words, was allowed to go into overdrive.

The work indicated how TTC5 uses the emerging protein as a beacon to find tubulin mRNAs for degradation.

Ivana Gasic in Tim Mitchisons lab at Harvard worked with Zhewang to show that if a working TTC5 is not present, meaning a cell cannot fine-tune its tubulin content, then the alignment and segregation of chromosomes is more prone to errors. They believe this is because tubulin plays a critical role in cell division.

It joins together to form microtubules, which control this key cellular event, along with cell movement and cell shape. Precise control of levels of tubulin is therefore vital.

Further experiments by Zhewang showed that TTC5 is not always available. It is normally sequestered hidden by an inhibitor, which has yet to be identified. It releases TTC5 only under conditions when cells detect too much free tubulin.

The researchers now hope to find this inhibitor and understand how it controls this process of sequestering and releasing TTC5.

Manus lab is also working to identify the machinery responsible for degrading mRNA when requested.

But the mechanism of the nascent protein acting like a beacon to find the tubulin mRNA is important.

Manu told the Cambridge Independent: Our discovery of a central component of the thermostat that regulates the production rate of tubulins allows us to begin understanding how such control systems operate inside the cell. Similar mechanisms are probably used to maintain other important proteins at optimal levels to keep cells healthy.

This work was funded by the MRC, the US National Institutes of Health, the Human Frontier Science Program, the Damon Runyon Cancer Research Foundation, Harvard Medical School, the Vallee Scholars Program, the Wellcome Trust, the Agouron Institute, and the Louis-Jeantet Foundation.

Read more

LMB unveils vision for next generation of Nobel Prize-winning cryo-EM technology

Worlds first synthetic organism with fully recoded DNA is created at MRC LMB in Cambridge

Tributes following the death of Kiyoshi Nagai, of the MRC Laboratory of Molecular Biology

Dr Jan Lwe on the next frontier for MRC Laboratory of Molecular Biology in Cambridge

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Housekeeping secrets of our cells are uncovered by the MRC LMB - Cambridge Independent

In an effort to address the critical public health need for new, safer and more effective medicines to treat pain, a consortium based at the Laboratory of Systems Pharmacology (LSP) at Harvard Medical School has launched an ambitious project titled STOP PAIN (Safe Therapeutic Options for Pain and Inflammation).

By combining a wide range of experimental and artificial intelligence-driven approaches, the consortium aims to identify compounds that selectively block the activity of nociceptors--the sensory neurons that sense and initiate pain--with the goal of developing new, preclinical drug candidates that offer an alternative to the opioid-based medications at the heart of the U.S. opioid epidemic.

The project is led by researchers from HMS and Boston Children's Hospital, with collaborators from Massachusetts Institute of Technology (MIT) and the Max Planck Institute for Medical Research in Germany.

It is supported by the U.S. Defense Advanced Research Projects Agency (DARPA) through the Panacea program, which aims to engender new therapies that address under-met medical needs of active duty soldiers and veterans. The DARPA cooperative agreement includes funding of up to $23,378,281.

The STOP PAIN consortium encompasses expertise across research disciplines, including neurobiology, systems pharmacology, stem cell biology, and computational and medicinal chemistry, and is led by:

We have substantial opportunities today to combine new laboratory methods, advanced chemistry and artificial intelligence and bring those tools to bear on the enormous societal, scientific and medical challenges of pain management.

Modern cancer care, for example, is now full of promising new medicines based on transformative science, yet if we look back two decades the field appeared to be stuck. We hope that advances in the science of sensation and computing will similarly shift the trajectory of drug development for pain."

Peter Sorger

According to the National Institute on Drug Abuse, an estimated 1.7 million Americans suffered from substance use disorders related to prescription opioid pain relievers in 2017 alone, and more than 47,000 died as a result of opioid overdose, leading government agencies to declare a nationwide public health emergency that year.

Prescription opioids are generally effective for the immediate and temporary treatment of severe pain, such as after trauma or surgery. However, they are only partially or not at all effective for chronic pain, and their prolonged use carries serious risks for developing tolerance, addiction and misuse.

Efforts to develop nonopioid pain therapies have been largely unsuccessful, highlighted, for example, by the high-profile recall of the prescription pain and inflammation drug Vioxx in 2014. Currently available medications such as acetaminophen and ibuprofen are not as effective as opioids and, when used long-term, can have adverse side effects that include gastrointestinal bleeding and liver damage.

Due to the lack of viable alternatives, prescription opioids remain a primary therapeutic option for the management of both acute and chronic pain.

"If we can successfully build better drugs to control pain, such that no physician would ever need to prescribe opioids because there would be safer and more effective options available, there would be an enormous impact on both the practice of medicine and on the societal catastrophe that the opioid epidemic has created," Woolf said. "As a consortium, we are keen to accept this challenge and to do everything possible to achieve this goal."

To identify new, nonopioid drug candidates, the STOP PAIN consortium is taking a unique approach that embraces the complexity of the biology of pain.

Current drug development processes in industry typically focus on screening for compounds that affect a single biological target--such as recent failed efforts to develop drugs targeting the protein Nav1.7, identified as defective in people with a congenital disorder that renders them insensitive to pain.

In contrast, the consortium will not begin with predetermined targets but instead focus on the activity of cells, specifically the nociceptor neurons responsible for initiating the sensation of pain.

"This project is based on the recognition that many of the most effective drugs for other neurological diseases have many molecular targets, not just one," Bean said. "Our goal is to systematically understand the complex network of molecules controlling the function of pain-sensing neurons and use that knowledge to design drug molecules that hit many targets, with the aim of safely and selectively inhibiting nociceptor function."

The team will screen for small molecule, nonopioid-based compounds that silence the activity of stem-cell derived human nociceptors under laboratory conditions.

The team will focus on compounds that exclusively block nociceptor function, while leaving the activity of other cell types, such as motor neurons or heart cells, unaffected. This selective targeting is a key preclinical marker of safety and specificity. These compounds then will be comprehensively analyzed for their molecular and biological characteristics, including effects on gene expression, protein production and cell physiology.

These data will be combined with insights drawn from INDRA (Integrated Network and Dynamical Reasoning Assembler), a powerful artificial intelligence system developed at the LSP, which automatically parses the scientific literature and public databases to construct models of gene and protein networks that can then be tested in the lab.

Together, these analyses aim to articulate the precise molecular mechanisms by which compounds inhibit nociceptor function and reveal the specific molecular targets involved in order to inform further drug development.

Once fully characterized, promising compounds will be refined or redesigned through computational and experimental chemistry techniques to maximize their potential efficacy.

The compounds will then be tested for safety and efficacy for pain management in preclinical models and through new machine vision and learning tools developed by the consortium.

By integrating these complementary approaches, the STOP PAIN consortium intends to generate thoroughly evaluated drug candidates for submission to the U.S. Food and Drug Administration for Investigational New Drug designation.

In addition, the team believes that the shift from a target-based approach to a cell-based screening approach backed up by sophisticated computational modeling could help transform the process of drug discovery and validation by offering an alternative model to address other critical unmet therapeutic needs.

Drug development is notoriously slow and arduous, but the researchers say they are optimistic that the depth and breadth of their collective expertise--drawn from multiple disciplines and institutions--makes it possible to develop drug candidates suitable for human clinical trials within the five-year time frame of the project. As one measure of progress, new compounds are already being synthesized and tested by the team.

This project is closely aligned with the recently launched Therapeutics Initiative at HMS, which aims to expedite the translation of basic science discoveries into new treatments for patients.

To this end, the consortium will pursue development of the most promising drug candidates through new ventures or collaborations with existing pharmaceutical or biotech companies. This includes working with life sciences incubators such as the Pagliuca Harvard Life Lab or the recently announced Blavatnik Harvard Life Lab Longwood, which both support early-stage, high-potential biotech and life sciences projects from the Harvard community.

"The development of safer medications to replace prescription opioids for pain management remains one of the most pressing unmet needs in medicine," said George Q. Daley, Dean of HMS. "This ambitious multi-institutional consortium offers promise for improving the health and well-being of countless patients and families."

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LOUISVILLE, Ky.--(BUSINESS WIRE)-- The National Stem Cell Foundation (NSCF) announced today that research teams from Aspen Neuroscience and the New York Stem Cell Foundation (NYSCF) Research Institute will send a first-in-kind study of neurodegenerative disease to the International Space Station (ISS) on the nineteenth SpaceX Commercial Resupply Services (CRS-19) mission, scheduled to launch December 4th from the Kennedy Space Center in Cape Canaveral, Florida. This is the second space flight for the research teams. A preliminary experiment was launched to the ISS in July 2019 onboard SpaceX CRS-18 to test custom flight hardware systems and refine post-flight analytical methods in preparation for the SpaceX CRS-19 launch.

The NSCF-funded collaboration between researchers at the NYSCF Research Institute and Aspen Neuroscience will perform the first study of long-term cell cultures of patient-derived induced pluripotent stem cell (iPSC) neural organoids with microglia on the ISS to study Parkinsons disease and primary progressive multiple sclerosis in microgravity. The ability to observe cell interaction, cell signaling, migration, changes in gene expression and the common pathways of neuroinflammation for both diseases in microgravity provides an opportunity to view the biological processes in a way that is not possible on Earth. This innovative approach to modelling disease has the potential to provide valuable new insight into the fundamental mechanisms underlying neurodegenerative disorders that may accelerate biomarker discovery and potential new drug and cell therapy options for patients. These models also offer potential for better translational study and future personalized medicine applications.

The development of patient-specific, 3-dimensional human organoids that incorporate microglia (the inflammatory cells of the immune system implicated in the development of Parkinsons, MS and other neurodegenerative diseases) for observation and study in the unique research environment of microgravity has the potential to enable progress across the field for a wide variety of conditions that affect a significant portion of the global population. The engineering required to facilitate the transport of cells and culture on orbit is being led by space flight engineering partner Space Tango.

Dr. Paula Grisanti, CEO of NSCF said, Supporting this collaboration between world-class research teams during a time of explosive growth in our understanding of the research advances possible in space is a great privilege. We are delighted to be funding such innovative science at the frontier of new drug and cell therapy discovery.

We are thrilled to be working with such a comprehensive team of scientists and fantastic organizations and feel honored to use our technology to better understand neurodegenerative disorders affecting so many persons globally, said Dr. Andres Bratt-Leal, Vice President of Research and Development, Aspen Neuroscience.

We feel privileged to have the opportunity to help understand the behavior of neural cells in microgravity and to help model neurodegenerative disease in such a novel way. We are excited about this fantastic project and look forward to learning the results, said Dr. Jeanne Loring, Chief Scientific Officer, Aspen Neuroscience.

We are excited to collaborate on the first study of progressive multiple sclerosis and Parkinsons patient brain cells in space. This work will provide important insights into the mechanisms behind these diseases and advance targets for future treatments," noted Susan L. Solomon, NYSCF Chief Executive Officer.

There is significant potential to advance our understanding of MS and PD as we initiate these long-term studies of patient cells in microgravity now that we have completed our preliminary tests, said Dr. Valentina Fossati, NYSCF Senior Research Investigator. We look forward to leveraging the unique capabilities of spaceflight research to better understand the role of microglia in multiple sclerosis and Parkinsons disease, as well as how dysfunction in these cells can be targeted therapeutically.

It takes vision, passion, and courage to change the paradigms of current understanding, said Jana Stoudemire, Commercial Innovation Officer at Space Tango. We are honored to support the groundbreaking work of the National Stem Cell Foundation and these recognized leaders in stem cell biology. Their commitment and dedication to advancing the frontiers of science using new tools and new approaches has been inspiring to witness, and has the potential to provide an entirely new perspective on Parkinsons and progressive MS.

To learn more about this unique collaboration, visit https://www.stemcellsinspace.org/.

About The National Stem Cell Foundation (NSCF)

The National Stem Cell Foundation is a 501(c)3 non-profit organization that funds adult stem cell and regenerative medicine research, connects children with limited resources to clinical trials for rare diseases and underwrites the National STEM Scholar Program for middle school science teachers inspiring the next generation of STEM (science, technology, engineering and math) pioneers nationwide. For more information, visit https://nationalstemcellfoundation.org/.

About The New York Stem Cell Foundation (NYSCF) Research Institute

The New York Stem Cell Foundation Research Institute is an independent organization accelerating cures and better treatments for patients through stem cell research. The NYSCF global community includes over 180 researchers at leading institutions worldwide, including NYSCF Druckenmiller Fellows, NYSCF Robertson Investigators, NYSCF Robertson Stem Cell Prize Recipients, and NYSCF Research Institute scientists and engineers. The NYSCF Research Institute is an acknowledged world leader in stem cell research and in developing pioneering stem cell technologies, including the NYSCF Global Stem Cell Array and in enabling large-scale stem cell research for scientists around the globe. NYSCF focuses on translational research in a model designed to overcome the barriers that slow discovery and replace silos with collaboration. For more information, visit http://www.nyscf.org.

About Aspen Neuroscience, Inc.

Aspen Neuroscience is a development stage, private biotechnology company that uses innovative genomic approaches combined with stem cell biology to deliver patient-specific, restorative cell therapies that modify the course of Parkinsons disease. The pipeline technology of Aspen is based upon the scientific work of world-renowned stem cell scientist, Dr. Jeanne Loring, who has developed a novel method for autologous neuron replacement. For more information and important updates, please visit http://www.aspenneuroscience.com.

About Space Tango, Inc.

Space Tango provides improved access to microgravity through their Open Orbit platform for bioengineering and manufacturing applications that benefit life on Earth. With their first operational TangoLab facility installed on the International Space Station in 2016, and a second facility installed in 2017, Space Tango has designed and flown nearly 80 diverse payloads. As a recognized leader in the development of fully automated, remote-controlled systems for research and manufacturing in orbit, Space Tango continues to provide expertise in technology and scientific consulting for industry and academic partners. Leveraging this current work, Space Tango is developing new commercial market segments in space with the announcement of ST-42 a fully autonomous orbital platform designed specifically for scalable manufacturing in space. Space Tango envisions a future where the next important breakthroughs in both technology and healthcare will occur off the planet, creating a new global market 250 miles up in low Earth orbit. For more information, visit http://www.spacetango.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191202005500/en/

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First-in-kind Human 3-dimensional Models of Parkinson's Disease and Progressive Multiple Sclerosis Launching to the International Space Station -...

A study has demonstrated how mutations in early colon cancer prevail and grow into malignancies, using fluorescent imaging.

Researchers have revealed how stem cell mutations arise and spread throughout a widening field of the colon until they eventually become a malignancy. According to the team, their technique could lead to therapeutic developments and earlier treatment of the disease.

High magnification image of fluorescent intestinal stem cells. Each fluorescent colour is used as a barcode to visualise human colon cancer-causing mutations in mice (credit: Duke Health).

The study was conducted at the Duke Cancer Institute at Duke University, US.

Using an innovative modelling system in mice, the researchers visually tagged colon cancer mutations by causing stem cells to grow. This allowed them to identify the prevailing mutations, which could be visualised in the animals.

The team tagged several common colon cancer mutations in the stem cells of a single tumour to create a fluorescent barcode. When transferred to a mouse, the colours of the stem cells could be tracked, revealing the cellular and molecular dynamics of the pre-cancerous events.

The researchers suggest that their technique can be used to discover field cancerisation, which is suggested to be the defining event that initiates the process of cancer growth.

This study provides new insight into the previously invisible process in which mutant pre-cancerous stem cells spread throughout the colon and seed cancer, said Dr Joshua Snyder, Assistant Professor in the Departments of Surgery and Cell Biology at Duke and corresponding and co-senior author.

Our technique sets a firm foundation for testing new therapies that interrupt this early, pre-malignant process. We hope to one day target and eliminate these stealth precancerous cells to prevent cancer, Snyder continued.

The findings were published in Nature Communications.

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