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  • richardmitnick 9:54 am on March 9, 2017 Permalink | Reply
    Tags: , , Personal Genome Project, WYSS Institute   

    From Wyss: “Wyss Institute and Lumos Labs Launch Research Collaboration on Memory of High Performing Individuals” 

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    Wyss Institute

    March 9, 2017
    Eriona Hysolli

    Personal Genome Project will integrate brain training tests to help identify key memory genes towards understanding neurodegeneration.

    Researchers at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS)’s Personal Genome Project (PGP) announced today a new collaboration with Lumos Labs, makers of brain training program Lumosity. The PGP-Lumosity memory project aims to leverage the PGP’s and Lumos Labs’ unique resources and expertise to investigate the relationship between genetics and memory, attention and reaction speed.

    Wyss scientists plan to recruit 10,000 members from the PGP which started in 2005 in the laboratory of George Church, PhD, a founding Core Faculty member of the Wyss Institute and also Professor of Genetics at Harvard Medical School. Participants in the PGP publicly share their genome sequences, biospecimens and healthcare data for unrestricted research on genetic and environmental relationships to disease and wellness. Wyss Institute researchers will use a select set of cognitive tests from Lumos Labs’ NeuroCognitive Performance Test (NCPT), a brief, repeatable, accessible web-based alternative to traditional pencil-paper cognitive assessments to evaluate participant’s memory functions, including their ability to recall objects, memorize object patterns, and response times.

    Church’s research team at the Wyss Institute and HMS Postdoctoral Fellows Elaine Lim, Ph.D., and Rigel Chan, Ph.D., will correlate extremely high performance scores with naturally-occurring variations in the participants’ genomes. “Our goal is to get people who have remarkable memory traits and engage them in the PGP. If you are exceptional in any way, you should share it not hoard it,” said Church.

    To validate their findings, the team will take advantage of the Wyss Institute’s exceptional abilities to sequence, edit and visualize DNA, model neuronal development in 3D brain organoids ex vivo, and, ultimately, to test emerging hypotheses in experimental models of neurodegeneration.

    “The Wyss Institute’s extraordinary scientific program and the Personal Genome Project’s commitment to research that is both pioneering and responsible make them ideal collaborators,” said Bob Schafer, Ph.D., Director of Research at Lumos Labs. “Combining Lumosity’s potential as a research tool could help us learn more about how our online assessment can help power innovative, large-scale studies.”

    Drs. Church, Lim and Chan plan to begin recruitment for this study in early March.

    The PGP-Lumosity memory project is the latest in a long line of exciting research collaborations supported by each platform. Through their Human Cognition Project, Lumos Labs is currently working with independent researchers at over 60 different institutions and investigating a range of topics, including normal aging, certain clinical conditions and the relationship between exercise and Lumosity training. Existing collaborative projects available to PGP participants include stem cell banking with the New York Stem Cell Foundation, “Go Viral” real-time Cold & Flu surveillance, the biology of Circles with Harvard Medical School, Genetics of Perfect pitch with the Feinstein Institute for Medical Research, characterizing the human microbiome in collaboration with American Gut, and discounted whole genome sequencing strategies.

    With the PGP’s aim to serve as a portal that empowers the public to drive scientific discovery through their participation, this collaboration is a synergistic convergence of two uniquely positioned organizations that combine science with broad outreach.

    “What excites us about this project is opening up groundbreaking technologies developed at the Wyss Institute to explore the relationship between genetics and memory with possible implications for Alzheimer’s and other diseases,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at Harvard SEAS.

    For more information or to register in the study, please visit: https://wyss.harvard.edu/pgp-lumosity

    See the full article here .

    Please help promote STEM in your local schools.

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    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 3:19 pm on February 4, 2017 Permalink | Reply
    Tags: , , Coxsackievirus B1, Enteroviruses, , WYSS Institute, Wyss Institute’s human gut-on-a-chip goes viral   

    From Wyss: “Wyss Institute’s human gut-on-a-chip goes viral” 

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    Wyss Institute

    February 1, 2017
    No writer credit found

    Enteroviruses enter the human body through the digestive or respiratory tract and from there spread to other sites in the body where they can cause a variety of serious health threats including meningitis, pancreatitis, myocarditis, the death of motor neurons, and perhaps even help trigger diabetes. However, they remain a challenge to study because they cannot be grown in conventional human cell cultures. Yet, understanding how enteroviruses invade gastrointestinal cells, multiply within them, and are released to other sites in the body could be key to ending the present dearth of specific anti-viral therapies and vaccines.

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    As shown in these immunofluorescence images, the research team recapitulated the typical epithelial microvilli architecture of the human gut in a microchannel of a microfluidic chip with cell nuclei shown in blue and the cytoskeleton that enables each cell to assume and maintain its shape in the microvilli structure shown in red (left image). Upon infection with a clinical Coxsackievirus B1 strain (green), the epithelium produced and secreted additional viral particles that induced the break-down of the tissue’s normal architecture. Credit: Wyss Institute at Harvard University.

    Towards solving this problem, a multidisciplinary team of tissue engineers and biologists at Harvard’s Wyss Institute for Biologically Inspired Engineering working alongside scientists from the Molecular Virology Team at the U.S. Food and Drug Administration (FDA)’s Center for Food Safety and Applied Nutrition now have leveraged the Wyss Institute’s previously developed human gut-on-a-chip to mimic the entry, host cell-interaction and multiplication of a pathogenic clinical strain of Coxsackievirus using gut epithelium outside the human body. Their findings are reported in PLoS One.

    “We teamed up with FDA researchers to show for the first time that an enterovirus can be successfully cultured in a microfluidic human Gut Chip system. We were excited to find that the organ-on-a-chip approach offers a potential new way to study these viral pathogens under more physiologically relevant conditions in vitro,” said the Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who led the team. Ingber also is the Judah Folkman Professor of Vascular Biology at Boston Children’s Hospital and Harvard Medical School, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

    “Now that we have a functional minimal system in place that replicates typical host-pathogen interactions, we can start to vary the type of intestinal cells, include immune cells that may contribute to the host response to infection, or create tissues using human stem cell-derived intestinal cells to tease out virus specificities and requirements for infection,” said Ingber.

    First developed in 2012, the Wyss Institute’s human gut-on-a-chip is a transparent, hollow-channeled microfluidic device the size of a computer memory stick that recapitulates the gut microenvironment. Human intestinal epithelial cells are cultured in a microchannel on a porous membrane that separates them from a parallel microchannel that mimics a neighboring capillary blood vessel. Fluid with or without viruses is flowed through both channels and exchanged through the pores of the membrane. Suction forces are also applied to parallel hollow channels, which produce cyclic deformations in the tissue that mimic intestinal peristalsis-like motions. This culture approach results in the growth of a fully differentiated gut epithelium that exhibits three-dimensional finger-like villus structures and that harbors all of the relevant cell types of the small intestine. In 2015, the team added more complexity to their biomimicking device by co-culturing a capillary endothelium on the lower surface of the membrane as well as a bacterial gut microbiome on the lumen of the epithelial channel to model aspects of human intestinal inflammation.

    “We were able to recapitulate how Coxsackievirus B1 enters the epithelium lining the intestinal villi from the gut lumen, and show that the virus replicates inside the cells and exits them again via a specific route to go on to infect cells downstream in the channel,” said Remi Villenave, Ph.D., the study’s first author who did the work when he was a postdoctoral fellow working with Ingber. “Also inflammatory cytokines that likely contribute to intestinal tissue injury in the chip were preferentially secreted into the lumen of the intestinal channel rather than into the media transporting channel, paralleling what is seen in acute infections in people.”

    Besides Villenave and Ingber, the article is also authored by FDA researchers Samantha Wales, Efstathia Papafragkou, Christopher Elkins and Michael Kulka. Additional authors are Tiama Hamkins-Indik, James Weaver, Thomas Ferrante and Anthony Bahinski, who at the time of the study were affiliated with the Wyss Institute.

    See the full article here .

    Please help promote STEM in your local schools.

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    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 2:11 pm on January 19, 2017 Permalink | Reply
    Tags: , , Soft robot helps the heart beat, WYSS Institute   

    From Wyss: “Soft robot helps the heart beat” 

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    Wyss Institute

    January 18, 2017
    Leah Burrows

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    This image shows a soft robotic sleeve placed around the heart in a pig model of acute heart failure. The actuators embedded in the sleeve support heart function by mimicking the outer heart muscles that induce the heart to beat. Credit: Harvard SEAS

    Harvard University and Boston Children’s Hospital researchers have developed a customizable soft robot that fits around a heart and helps it beat, potentially opening new treatment options for people suffering from heart failure.

    The soft robotic sleeve twists and compresses in synch with a beating heart, augmenting cardiovascular functions weakened by heart failure. Unlike currently available devices that assist heart function, Harvard’s soft robotic sleeve does not directly contact blood. This reduces the risk of clotting and eliminates the need for a patient to take potentially dangerous blood thinning medications. The device may one day be able to bridge a patient to transplant or to aid in cardiac rehabilitation and recovery.

    “This research demonstrates that the growing field of soft robotics can be applied to clinical needs and potentially reduce the burden of heart disease and improve the quality of life for patients,” said Ellen T. Roche, Ph.D., the study’s first author and a former Graduate Student at the Wyss Institute of Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). Roche is currently a Postdoctoral Fellow at the National University of Ireland.

    The research, published in Science Translational Medicine, was a collaboration between the Wyss Institute, SEAS and Boston Children’s Hospital.

    “This work represents an exciting proof of concept result for this soft robot, demonstrating that it can safely interact with soft tissue and lead to improvements in cardiac function. We envision many other future applications where such devices can delivery mechanotherapy both inside and outside of the body,” said Conor Walsh, Ph.D., senior author of the paper, who is a Wyss Institute Core Faculty member and the John L. Loeb Associate Professor of Engineering and Applied Sciences at SEAS.

    Heart failure affects 41 million people worldwide. Today, some of the options to treat it are mechanical pumps called ventricular assist devices (VADs), which pump blood from the ventricles into the aorta, and heart transplants. While VADs are continuously improving, patients are still at high risk for blood clots and stroke.

    To create an entirely new device that doesn’t come into contact with blood, Harvard researchers took inspiration from the heart itself. The thin silicone sleeve uses soft pneumatic actuators placed around the heart to mimic the outer muscle layers of the mammalian heart. The actuators twist and compress the sleeve in a similar motion to the beating heart.

    The device is tethered to an external pump, which uses air to power the soft actuators.

    The sleeve can be customized for each patient, said Roche. If a patient has more weakness on the left side of the heart, for example, the actuators can be tuned to give more assistance on that side. The pressure of the actuators can also increase or decrease over time, as the patient’s condition evolves.

    The sleeve is attached to the heart using a combination of a suction device, sutures and a gel interface to help with friction between the device and the heart.

    The Wyss and SEAS engineers worked with surgeons at Boston Children’s Hospital to develop the device and determine the best ways to implant the device and test it on animal models.

    “The cardiac field had turned away from idea of developing heart compression instead of blood-pumping VADs due to technological limitations, but now with advancements in soft robotics it’s time to turn back,” said Frank Pigula, M.D., a cardiothoracic surgeon and co-corresponding author on the study, who was formerly Clinical Director of pediatric cardiac surgery at Boston Children’s Hospital and is now a Faculty Member at University of Louisville and division chief of pediatric cardiac surgery at Norton Children’s Hospital. “Most people with heart failure do still have some function left; one day the robotic sleeve may help their heart work well enough that their quality of life can be restored.”

    More research needs to be done before the sleeve can be implanted in humans but the research is an important first step towards an implantable soft robot that can augment organ function.

    Harvard’s Office of Technology Development has filed a patent application and is actively pursuing commercialization opportunitities.

    “This research is really significant at the moment because more and more people are surviving heart attacks and ending up with heart failure,” said Roche. “Soft robotic devices are ideally suited to interact with soft tissue and give assistance that can help with augmentation of function, and potentially even healing and recovery.”

    The research was co-authored by Markus A. Horvath, Isaac Wamala, Ali Alazmani, Sang-Eun Song, William Whyte, Zurab Machaidze, Christopher J. Payne, James Weaver, Gregory Fishbein, Joseph Kuebler, Nikolay V. Vasilyev and David J. Mooney.

    It was supported by a Director’s Challenge Cross-Platform grant from the Wyss Institute for Biologically Inspired Engineering, a Translational Research Program grant from Boston Children’s Hospital, the Harvard School of Engineering and Applied Sciences and the Science Foundation Ireland.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 4:02 pm on January 16, 2017 Permalink | Reply
    Tags: , , Connectome project, , Multiregional brain-on-a-chip, WYSS Institute   

    From Wyss: “Multiregional brain on a chip” 

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    Wyss Institute

    January 14, 2017
    Leah Burrows

    Model allows researchers to study how diseases like schizophrenia impact different regions of the brain simultaneously.

    Harvard University researchers have developed a multiregional brain-on-a-chip that models the connectivity between three distinct regions of the brain. The in vitro model was used to extensively characterize the differences between neurons from different regions of the brain and to mimic the system’s connectivity.

    The research was published in the Journal of Neurophysiology.

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    Three areas populated with neurons representing different regions of the brain are interconnected by thin neuronal process (in green) to allow the study of complex diseases. Credit: Disease Biophysics Group/Harvard University

    “The brain is so much more than individual neurons,” said Ben Maoz, co-first author of the paper and a Technology Development Fellow at the Wyss Institute for Biologically Inspired Engineering, and Postdoctoral Fellow in the Disease Biophysics Group in the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS). “It’s about the different types of cells and the connectivity between different regions of the brain. When modeling the brain, you need to be able to recapitulate that connectivity because there are many different diseases that attack those connections.”

    “Roughly twenty-six percent of the US healthcare budget is spent on neurological and psychiatric disorders,” said Wyss Institute Core Faculty member Kit Parker and the Tarr Family Professor of Bioengineering and Applied Physics Building at SEAS. “Tools to support the development of therapeutics to alleviate the suffering of these patients is not only the human thing to do, it is the best means of reducing this cost.”

    Researchers from the Wyss Institute and the Disease Biophysics Group at SEAS modeled three regions of the brain most affected by schizophrenia — the amygdala, hippocampus and prefrontal cortex.

    They began by characterizing the cell composition, protein expression, metabolism, and electrical activity of neurons from each region in vitro.

    “It’s no surprise that neurons in distinct regions of the brain are different but it is surprising just how different they are,” said Stephanie Dauth, co-first author of the paper and former postdoctoral fellow in the Disease Biophysics Group. “We found that the cell-type ratio, the metabolism, the protein expression and the electrical activity all differ between regions in vitro. This shows that it does make a difference which brain region’s neurons you’re working with.”

    Next, the team looked at how these neurons change when they’re communicating with one another. To do that, they cultured cells from each region independently and then let the cells establish connections via guided pathways embedded in the chip.

    The researchers then measured cell composition and electrical activity again and found that the cells dramatically changed when they were in contact with neurons from different regions.

    “When the cells are communicating with other regions, the cellular composition of the culture changes, the electrophysiology changes, all these inherent properties of the neurons change,” said Maoz. “This shows how important it is to implement different brain regions into in vitro models, especially when studying how neurological diseases impact connected regions of the brain.”

    To demonstrate the chip’s efficacy in modeling disease, the team doped different regions of the brain with the drug Phencyclidine hydrochloride — commonly known as PCP — which simulates schizophrenia. The brain-on-a-chip allowed the researchers for the first time to look at both the drug’s impact on the individual regions as well as its downstream effect on the interconnected regions in vitro.

    The brain-on-a-chip could be useful for studying any number of neurological and psychiatric diseases, including drug addiction, post traumatic stress disorder, and traumatic brain injury.

    “To date, the Connectome project has not recognized all of the networks in the brain,” said Parker. “In our studies, we are showing that the extracellular matrix network is an important part of distinguishing different brain regions and that, subsequently, physiological and pathophysiological processes in these brain regions are unique. This advance will not only enable the development of therapeutics, but fundamental insights as to how we think, feel, and survive.”

    This research was coauthored by Sean P. Sheehy, Matthew A. Hemphill, Tara Murty, Mary Kate Macedonia, Angie M. Greer and Bogdan Budnik. It was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Defense Advanced Research Projects Agency.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 1:03 pm on September 22, 2016 Permalink | Reply
    Tags: , , Just add water: Biomolecular manufacturing ‘on-the-go’, WYSS Institute   

    From Wyss: “Just add water: Biomolecular manufacturing ‘on-the-go’” 

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    Wyss Institute

    Sep 22, 2016
    PRESS CONTACT

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Kat J. McAlpine
    katherine.mcalpine@wyss.harvard.edu
    +1 617-432-8266

    MULTIMEDIA CONTACT

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Seth Kroll
    seth.kroll@wyss.harvard.edu,
    +1 617-432-7758

    Wyss Institute team unveils a low-cost, portable method to manufacture biomolecules for a wide range of vaccines, other therapies as well as diagnostics

    Even amidst all the celebrated advances of modern medicine, basic life-saving interventions are still not reaching massive numbers of people who live in our planet’s most remote and non-industrialized locations. The World Health Organization states that one half of the global population lives in rural areas. And according to UNICEF, last year nearly 20 million infants globally did not receive what we would consider to be basic vaccinations required for a child’s health.

    These daunting statistics are largely due to the logistical challenge of transporting vaccines and other biomolecules used in diagnostics and therapy, which conventionally require a “cold chain” of refrigeration from the time of synthesis to the time of administration. In remote areas lacking power or established transport routes, modern medicine often cannot reach those who may need it urgently.

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    The portable biomolecular manufacturing method, developed by Wyss Institute Core Faculty member James Collins and his team, can produce a broad range of biomolecules, including vaccines, antimicrobial peptides and antibody conjugates, without power or refrigeration. The team envisions that the method’s freeze-dried components could be carried in portable kits (such as the mock kit pictured here) for use in the field anywhere in the world. Credit: Wyss Institute at Harvard University

    A team of researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering has been working toward a paradigm-shifting goal: a molecular manufacturing method that can produce a broad range of biomolecules, including vaccines, antimicrobial peptides and antibody conjugates, anywhere in the world, without power or refrigeration.

    Now, in a new paper published September 22 in Cell journal, the team has unveiled what they set out to deliver, a “just add water” portable method that affordably, rapidly, and precisely generates compounds that could be administered as therapies or used in experiments and diagnostics.

    “The ability to synthesize and administer biomolecular compounds, anywhere, could undoubtedly shift the reach of medicine and science across the world,” said Wyss Core Faculty member James Collins, Ph.D., senior author on the study, who is also Professor of Medical Engineering & Science and Professor of Biological Engineering at the Massachusetts Institute of Technology (MIT)’s Department of Biological Engineering. “Our goal is make biomolecular manufacturing accessible wherever it could improve lives.”

    The approach, called “portable biomolecular manufacturing” by Collins’ team, which also included Neel Joshi, Ph.D., a Wyss Core Faculty member and Associate Professor of Chemical and Biological Engineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS), hinges on the idea that freeze-dried pellets containing “molecular machinery” can be mixed and matched to achieve a wide variety of end-products. By simply adding water, this molecular machinery can be set in motion.

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    To activate the biomolecular manufacturing process, freeze-dried components need simply be rehydrated (as seen in this mock demonstration). Credit: Wyss Institute at Harvard University

    Compounds manufactured using the method could be administered in several ways to a patient, including injection, oral doses or topical applications. As described in the study, a vaccine against diphtheria was synthesized using the method and shown to successfully induce an antibody response against the pathogen in mice.

    Subsequently, the team envisions that the method could be employed to create batches of tetanus or flu shots routinely manufactured in remote clinics. Vaccines against emerging infectious disease outbreaks could quickly be mobilized in the field to contain spiraling epidemics. Episodes of food poisoning could be dosed orally with the production of neutralizing antibodies produced on the spot. Flesh wounds susceptible to infection could be applied with topical antimicrobial peptides generated on demand. In these manners, the team’s approach could be leveraged to design a vast number of different lifesaving measures.

    The approach is built upon work described in a seminal 2014 paper also published in Cell, when the team demonstrated that transcription and translation machinery could function in vitro, without being inside living cells, inside freeze-dried slips of ordinary paper embedded with synthetic gene networks.

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    The Wyss Institute team envisions that the compounds created using the portable manufacturing method could be administered to patients in a variety of ways, including injection (as seen in this mock demonstration), oral delivery, and topical application. Credit: Wyss Institute at Harvard University

    Building off that work, the novel manufacturing method employs two types of freeze-dried pellets containing different kinds of components. The first kind of pellet contains the cell-free “machinery” that will synthesize the end product. The second kind contains DNA instructions that will tell the “machinery” what compound to manufacture. When the two types of pellets are combined and rehydrated with water, the biomolecular manufacturing process is triggered. The second type of pellet can be customized to produce a wide range of final products.

    Since they are freeze-dried, the pellets are extremely stable and safe for long-term storage at room temperature for up to and potentially beyond one year.

    “This approach could — with very little training — put therapeutics and diagnostic tools in the hands of clinicians working in remote areas without power,” said Keith Pardee, Ph.D., a co-first author on the study who was a Wyss Research Scientist and is now an Assistant Professor in the Leslie Dan Faculty of Pharmacy at the University of Toronto. “Currently, distribution of life-saving doses of protein-based preventative and interventional medicines are often restricted by access to an uninterrupted chain of cold refrigeration, which many areas of the world lack.”

    The cost of the approach, at roughly three cents per microliter, could also give access to biomolecular manufacturing to researchers and educators who lack access to wet labs and other sophisticated equipment, impacting basic science beyond the immediately apparent promise in clinical applications.

    “Synthetic biology has been harnessed to increase efficiency of manufacturing of biological products for medical and energy applications in the past, however, this new breakthrough utterly changes the application landscape,” said Wyss Core Faculty member Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s SEAS. “It’s really exciting because this new biomolecular manufacturing technology potentially offers a way to solve the cold chain problem that still restricts delivery of vaccines and other important medical treatments to patients in the most far-flung corners of the world who need them the most.”

    In addition to Collins, Joshi, and Pardee, additional authors on the study include: Shimyn Slomovic, co-first author, Institute for Medical Engineering & Science (IMES) at MIT; Peter Nguyen, co-first author, Wyss Institute; Jeong Wook Lee, co-first author, IMES at MIT, Wyss Institute; Nina Donghia, co-author, Wyss Institute; Devin Burrill, co-author, Wyss Institute; Tom Ferrante, co-author, Wyss Institute; Fern McSorley, co-author, University of Ottawa; Yoshikazu Furata, co-author, IMES at MIT; Michael Lewandowski, co-author, Wyss Institute; and Christopher Boddy, co-author, University of Ottawa.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 12:20 pm on August 13, 2016 Permalink | Reply
    Tags: , Discrete Molecular Imaging (DMI) technology, DNA-PAINT technologies, From super to ultra-resolution microscopy, , WYSS Institute   

    From Wyss: “From super to ultra-resolution microscopy” 

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    Wyss Institute

    Jul 5, 2016 [Just showed up in social media.]
    PRESS CONTACTS

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Benjamin Boettner, benjamin.boettner@wyss.harvard.edu, +1 917-913-8051

    MULTIMEDIA CONTACT

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Seth Kroll, seth.kroll@wyss.harvard.edu, +1 617-432-7758

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    The image shows how the Discrete Molecular Imaging (DMI) technology visualizes densely packed individual targets that are just 5 nanometer apart from each other in DNA origami structures (see schematics on the left). The image on the top right shows a DMI-generated super-resolution image of a clear pattern of individual signals. In the image on the bottom right, three different target species within the same origami structure have been visualized using Exchange-PAINT-enhanced DMI method. Credit: Wyss Institute at Harvard University.

    Proteins mostly do not work in isolation but rather make up larger complexes like the molecular machines that enable cells to communicate with each other, move cargo around in their interiors or replicate their DNA. Our ability to observe and track each individual protein within these machines is crucial to our ultimate understanding of these processes. Yet, the advent of super-resolution microscopy that has allowed researchers to start visualizing closely positioned molecules or molecular complexes with 10-20 nanometer resolution is not powerful enough to distinguish individual molecular features within those densely packed complexes.

    A team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by Core Faculty member Peng Yin, Ph.D., has, for the first time, been able to tell apart features distanced only 5 nanometers from each other in a densely packed, single molecular structure and to achieve the so far highest resolution in optical microscopy. Reported on July 4 in a study in Nature Nanotechnology, the technology, also called “discrete molecular imaging” (DMI), enhances the team’s DNA nanotechnology-powered super-resolution microscopy platform with an integrated set of new imaging methods

    Last year, the opportunity to enable researchers with inexpensive super-resolution microscopy using DNA-PAINT-based technologies led the Wyss Institute to launch its spin-off Ultivue Inc.

    “The ultra-high resolution of DMI advances the DNA-PAINT platform one step further towards the vision of providing the ultimate view of biology. With this new power of resolution and the ability to focus on individual molecular features, DMI complements current structural biology methods like X-ray crystallography and cryo-electron microscopy. It opens up a way for researchers to study molecular conformations and heterogeneities in single multi-component complexes, and provides an easy, fast and multiplexed method for the structural analysis of many samples in parallel” said Peng Yin, who is also Professor of Systems Biology at Harvard Medical School.

    DNA-PAINT technologies, developed by Yin and his team are based on the transient binding of two complementary short DNA strands, one being attached to the molecular target that the researchers aim to visualize and the other attached to a fluorescent dye. Repeated cycles of binding and unbinding create a very defined blinking behavior of the dye at the target site, which is highly programmable by the choice of DNA strands and has now been further exploited by the team’s current work to achieve ultra-high resolution imaging.

    “By further harnessing key aspects underlying the blinking conditions in our DNA-PAINT-based technologies and developing a novel method that compensates for tiny but extremely disruptive movements of the microscope stage that carries the samples, we managed to additionally boost the potential beyond what has been possible so far in super-resolution microscopy,” said Mingjie Dai, who is the study’s first author and a Graduate Student working with Yin.

    In addition, the study was co-authored by Ralf Jungmann, Ph.D., a former Postdoctoral Fellow on Yin’s team and now a Group Leader at the Max Planck Institute of Biochemistry at the Ludwig Maximilian University in Munich, Germany.

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    In this image the “Wyss!” name has been visualized in a DNA origami display with the so-far highest resolution possible in optical imaging using Discrete Molecular Imaging (DMI) technology. Credit: Wyss Institute at Harvard University.

    The Wyss Institute’s scientists have benchmarked the ultra-high resolution of DMI using synthetic DNA nanostructures. Next, the researchers plan to apply the technology to actual biological complexes such as the protein complex that duplicates DNA in dividing cells or cell surface receptors binding their ligands.

    “Peng Yin and his team have yet again broken through barriers never before possible by leveraging the power of programmable DNA, not for information storage, but create nanoscale ‘molecular instruments’ that carry out defined tasks and readout what they analyze. This new advancement to their DNA-powered super-resolution imaging platform is an amazing feat that has the potential to uncover the inner workings of cells at the single molecule level using conventional microscopes that are available in common biology laboratories,” said Donald Ingber, M.D., Ph.D., who is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and also Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

    See the full article here .

    Please help promote STEM in your local schools.

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    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 9:54 am on June 14, 2016 Permalink | Reply
    Tags: , How to diagnose systemic infections much more quickly and reliably, , WYSS Institute   

    From Wyss: “How to diagnose systemic infections much more quickly and reliably” 

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    Wyss Institute bloc
    Wyss Institute

    Jun 14, 2016
    PRESS CONTACTS

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Benjamin Boettner, benjamin.boettner@wyss.harvard.edu, +1 917-913-8051

    MULTIMEDIA CONTACT

    Wyss Institute for Biologically Inspired Engineering at Harvard University
    Seth Kroll, seth.kroll@wyss.harvard.edu, +1 617-432-7758

    1
    In the pathogen detection technology, engineered FcMBL proteins coupled to magnetic beads (grey) specifically bind to carbohydrate molecules on the surface of life pathogens, like infectious E.coli bacteria (colored in blue) in this electron micrograph, or on fragments of dead pathogens circulating in the blood-stream. After isolation in a magnetic field, the total pathogenic material is quantified with a second FcMBL protein that is linked to a color-producing enzyme. Credit: Wyss Institute at Harvard University

    To date, there are no methods that can quickly and accurately detect pathogens in blood to allow the diagnosis of systemic bloodstream infections that can lead to life-threatening sepsis. The standard of care for detecting such blood-borne infections is blood culture, but this takes days to complete, only identifies pathogens in less than 30% of patients with fulminant infections, and it is not able to detect toxic fragments of dead pathogens that also drive the exaggerated inflammatory reactions leading to sepsis.

    Biomarkers that report elevated inflammation are used clinically in the treatment of patients with sepsis; however, they fail to distinguish inflammation triggered by infectious pathogens from that induced by non-infectious causes, such as burns, traumas and surgeries.

    Now, a Wyss Institute team led by Donald Ingber reports in eBioMedicine that it has filled this void with a rapid and specific diagnostic assay that could help physicians decide within an hour whether a patient has a systemic infection and should be hospitalized for aggressive intervention therapy. The potential of this assay to detect pathogen materials was demonstrated in both animal studies and a prospective human clinical study, whose results also suggest that it also could serve as a companion diagnostic to monitor the success of antibiotic and dialysis-like sepsis therapies.

    “Our pathogen detection technology solves both dilemmas: it quickly reports whether infectious pathogens are present in the body, even at early stages of infection before sepsis develops. And it can more specifically identify patients who have excessive inflammation due to systemic infection, rather than other causes,” said Donald Ingber, M.D., Ph.D., the Wyss Institute’s Founding Director, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. “This assay could become a real game changer in this clinical area, and it also should lead to more judicious use of antibiotics, helping to decrease the worrisome rise we are seeing in antibiotic-resistant organisms.”

    “In a cohort of emergency room patients with suspected sepsis, we saw that the assay picked up infection within an hour in 85% of patients who exhibited clinical symptoms of sepsis, and equally importantly, it did not falsely predict infection in healthy subjects or patients with inflammation triggered by other causes, such as trauma. On the other hand, blood cultures that we performed in parallel using the same samples only detected pathogens in 18% of the cases,” said Nathan Shapiro, M.D., Ph.D., Director of Translational Research in the Center for Vascular Biology Research at BIDMC, who worked with Ingber’s team to conduct the clinical study. “This highlights the advance this technology represents.”

    The diagnostic assay is built on FcMBL, a genetically engineered pathogen-binding protein previously developed by Ingber and Michael Super, a Wyss Senior Staff Scientist who co-leads the Institute’s pathogen-detecting effort. FcMBL binds to pathogens and pathogen-released fragments, known as Pathogen-Associated Molecular Patterns (PAMPs) by recognizing carbohydrate molecules on their surface.

    Previous efforts in Ingber’s team at the Wyss Institute have established FcMBL as a key component of an advanced dialysis-like, pathogen-extracting therapeutic device, and of a method for the fast retrieval of infectious pathogens from complex clinical samples to enable their identification and antibody susceptibilities.

    “In our latest work, we show that the FcMBL-based pathogen-detecting assay is considerably faster and more accurate than any other available assay for systemic infection. We are currently working to ready it for high-throughput use in clinical and point of care situations and to accelerate it even further,” said Mark Cartwright, Ph.D., a Staff Scientist at the Wyss Institute and a lead-author on the study.

    As a prerequisite to their clinical study, the Wyss Institute’s team had successfully tested the assay in rat and pig models of infection with pathogenic E. coli bacteria.

    “The animal models clearly told us that the assay can sensitively trace spikes of PAMPs released during antibiotic therapy, or residual infectious PAMP materials, even when no living bacteria circulate anymore in blood but they remain hidden inside internal organs. Thus, this assay could be an excellent tool for monitoring ongoing infection and responses to antibiotics and dialysis-like therapies for severe infections and sepsis,” said Mike Super, Ph.D.

    Together, the findings suggest that the FcMBL-based pathogen detection technology with its rapid handling time, high sensitivity and broad specificity towards infection-causing pathogens could provide a real-world advance to diagnose life-threatening infections in both clinical microbiology laboratories and point-of-care settings.

    The work was funded by the Wyss Institute and the Defense Advanced Research Project Agency (DARPA).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 12:29 pm on December 27, 2015 Permalink | Reply
    Tags: , , WYSS Institute   

    From Wyss: “Changing the fate of stem cells” 

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    Harvard bloc tiny

    Wyss Institute

    Nov 30, 2015 [This was just put up]
    Leah Burrows

    Temp 1
    These scanning electron microscopy images show a cross section of the novel fast-relaxing hydrogel developed by David Mooney and his team at the Wyss Institute and SEAS. The hydrogels mimic natural tissues properties and trigger stem cells to differentiate into osteoblasts (bone-forming cells). Credit: Wyss Institute at Harvard University/Harvard SEAS

    Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a new, more precise way to synthetically control differentiation of stem cells into bone cells by leveraging bioinspired hydrogels. This new technique has promising applications in the realm of bone regeneration, growth and healing. The research led by David Mooney, Ph.D., Wyss Institute Core Faculty member and Robert P. Pinkas Family Professor of Bioengineering at SEAS, was published on November 30 in Nature Materials.

    The extracellular matrix, a microenvironment of proteins and polymers that surrounds and connects cells, impacts a range of cellular behaviors including differentiation. For about a decade, researchers have been able to direct the fate of stem cells by tuning the mechanical stiffness of synthetic microenvironments such as hydrogels. Stem cells in more flexible hydrogels have been shown to differentiate into fat cells while those in stiffer hydrogels are more likely to differentiate into osteogenic (bone) cells.

    But tuning stiffness alone is not precise enough to overcome many of the challenges in differentiating and proliferating different types of stem cells. Only tuning the stiffness of a cell’s microenvironment assumes that the natural extracellular matrix behaves elastically like rubber. When force or stress is exerted on an elastic material, it is stored as energy, and when that force is removed the material bounces back to its original shape like a rubber band. In nature, however, extracellular matrices are not elastic — they are viscoelastic. Viscoelastic materials, such as chewing gum or Silly Putty, relax over time when force or stress is applied.

    “This work both provides new insight into the biology of regeneration, and is allowing us to design materials that actively promote tissue regeneration,” said Mooney.

    Mooney and his team decided to mimic the viscoelasticity of living tissue by developing a novel hydrogel containing tunable stress relaxation responses. When they put stem cells into this viscoelastic microenvironment and tuned the speed at which the gel relaxed, they observed dramatic changes in the behavior and differentiation of the cells.

    Temp 2
    In this scanning electron microscopy image, stem cells can be seen cultured on the novel fast-relaxing hydrogel. The properties of the hydrogel will direct the stem cells to differentiate into bone cells. The new hydrogel could potentially have important biomedical applications in bone regeneration, growth and healing. Credit: Wyss Institute at Harvard University/Harvard SEAS

    “We found that by increasing stress relaxation, especially combined with increased stiffness in the hydrogel, there is an increase of osteogenic differentiation,” said Luo Gu, Postdoctoral Fellow at SEAS and Wyss and co-first author on the paper. “With increased stress relaxation, there was also a decreases the differentiation of fat cells. This is the first time we’ve observed how stress relaxation impacts cell differentiation.”

    Not only did increased stress relaxation dramatically increase early osteogenic differentiation but those cells continued to develop toward full–fledged bone cells.

    One reason that fast–relaxing microenvironments promote more osteogenesis and form bone is that cells inside these matrices can mechanically remodel the matrix and more easily change shape, said Ovijit Chaudhuri, a former Postdoctoral Fellow at SEAS and Wyss and co–first author on the study. It may seem counterintuitive that bone cells need fast–relaxing environments to grow into fully–formed strong, stiff bones. However, the team observed that the natural microenvironment around bone fractures is very similar to the fastest–relaxing hydrogel the team developed in the lab.

    “Coagulated bone marrow and blood near a fracture are very viscous,” Gu said. “This is a good indication that in the natural environment, when a bone fracture is healing, it needs a really fast–relaxing matrix to assist in bone growth.”

    Although no single microenvironment parameter alone controls differentiation, Gu said, combined tuning of hydrogel stress relaxation responses with stiffness properties provides a new way to more precisely control stem cell differentiation and development. The next stage of the research is to test fast-relaxing hydrogels in vivo, to see if they promote bone healing.

    The work was funded by the National Institute of Health, the Einstein Foundation Berlin and Harvard MRSEC.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Wyss Institute campus

    The Wyss (pronounced “Veese”) Institute for Biologically Inspired Engineering uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world.

    Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs.

     
  • richardmitnick 9:36 am on October 3, 2015 Permalink | Reply
    Tags: , , , , WYSS Institute   

    From Wyss Institute at Harvard: “How stem-cell research has received a boost” 

    Harvard University

    Harvard University

    Harvard Wyss Institute
    Wyss Institute

    Sep 18 2015
    Benjamin Boettner
    Kat J. McAlpine

    1

    Possible stem cell therapies often are limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the cell types needed to repair or replace injured tissues. A team led by David Mooney, a core faculty member at Harvard’s Wyss Institute, has now developed a strategy that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation. The method embeds stem cells into porous, transplantable hydrogels.

    In addition to Mooney, the team included Georg Duda, a Wyss associate faculty member and director of the Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration at Charité – Universitätsmedizin in Berlin, and Wyss Institute founding director Donald Ingber. The team published its findings in today’s issue of Nature Materials. Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

    Stem cell therapies have potential for repairing many tissues and bones, or even for replacing organs. Tissue-specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the lab, stem cells must survive and function properly after transplantation. Getting them to do so has been a major challenge for researchers.

    Mooney’s team and other researchers have identified specific chemical and physical cues from the stem cell niche (the area in which stem cells survive and thrive with support from other cell types and environmental factors) to promote stem cell survival, multiplication and maturation into tissue. Whereas chemical signals that control stem cell behavior are increasingly understood, much less is known about the mechanical properties of stem cell niches. Stem cells like those present in bone, cartilage, or muscle cultured in laboratories, however, have been found to possess mechanosensitivities, meaning they require a physical substrate with defined elasticity and stiffness to proliferate and mature.

    “So far these physical influences had not been efficiently harnessed to propel real-world regeneration processes,” said Nathaniel Huebsch, a graduate student who worked with Mooney and who is the study’s first author. “Based on our experience with mechanosensitive stem cells, we hypothesized that hydrogels could be leveraged to generate the right chemical and mechanical cues in a first model of bone regeneration.”

    Two water-filled hydrogels with very different properties are the key to the Mooney team’s method. A more stable, longer-lasting “bulk gel” is filled with small bubbles of a second, so-called “porogen” that degrades at a much faster rate, leaving behind porous cavities.

    By coupling the bulk gel with a small “peptide” derived from the extracellular environment of genuine stem cell niches, and mixing it with a tissue-specific stem cell type as well as the porogen, the team can create a bone-forming artificial niche. While the bulk gel provides just the right amount of elasticity plus a relevant chemical signal to coax stem cells to proliferate and mature, the porogen gradually breaks down, leaving open spaces into which the stem cells expand before they naturally migrate out of the gel structure altogether to form actual mineralized bone tissue.

    In small-animal experiments conducted so far, the researchers show that a void-forming hydrogel with the correct chemical and elastic properties provides better bone regeneration than transplanting stem cells alone. Of further interest, the maturing stem cells deployed by the hydrogel also induce nearby native stem cells to contribute to bone repair, further amplifying their regenerative effects.

    “This study provides the first demonstration that the physical properties of a biomaterial can not only help deliver stem cells but also tune their behavior in vivo,” said Mooney. “While so far we have focused on orchestrating bone formation, we believe that our hydrogel concept can be broadly applied to other regenerative processes as well.”

    The collaborative, cross-disciplinary work was supported by the Harvard University Materials Research Science and Engineering Center (MRSEC), which is funded by the National Science Foundation (NSF).

    “This is an exquisite demonstration of MRSEC programs’ high impact,” said Dan Finotello, program director at the NSF. “MRSECs bring together several researchers of varied experience and complementary expertise who are then able to advance science at a considerably faster rate.”

    Additional funding was provided by the National Institutes of Health; the Belgian American Education Foundation; the Einstein Foundation Berlin; the Berlin-Brandenburg School for Regenerative Therapies; the Harvard College Research Program; and NSF Graduate Research, Einstein Visiting, Harvard College PRISE, Herchel-Smith and Pechet Family Fund Fellowships.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

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    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

     
  • richardmitnick 9:22 am on August 21, 2015 Permalink | Reply
    Tags: , , , , WYSS Institute   

    From Wyss at Harvard: Wyss improves sepsis device 

    Harvard University

    Harvard University

    Wyss Institute

    August 20, 2015
    Kat J. McAlpine

    1
    This blood-cleansing device connected to a dialysis-like circuit has a dense pack of hollow fibers whose inner surfaces are covered with the Wyss Institute’s genetically engineered Mannose-binding lectin (MBL) protein, called FcMBL. When septic blood is streamed through the device, FcMBL effectively extracts viruses, fungi, and parasites as well as toxins and dead pathogen fragments released into the bloodstream by antibiotic killing. Image courtesy of the Wyss Institute

    New model of blood-cleansing device has been simplified and is closer to clinical use

    A team of scientists at the Wyss Institute last year described the development of a device to treat sepsis that works by mimicking the human spleen. The device cleanses pathogens and toxins from blood flowing through a dialysis-like circuit. Now the team has developed an improved device that works with conventional antibiotic therapies and is better positioned for near-term use in clinics.

    The improved design is described in the October issue of Biomaterials.

    Sepsis is a common and frequently fatal medical complication that can occur when the body attempts to fight off serious infection and the resulting widespread inflammation can cause organs to shut down, blood pressure to drop, and the heart to weaken. This can lead to septic shock, which eventually kills more than 30 percent of septic patients in the United States. In most cases, the pathogen responsible for triggering the septic condition is not pinpointed, so clinicians blindly prescribe an antibiotic course in a blanket attempt to stave off the infectious bacteria and halt the dangerous inflammatory response.


    Download here.
    This video explains how sepsis induced by an overload of blood pathogens can be treated with the Wyss Institute’s improved pathogen-extracting, spleen-mimicking device. Blood is flown through a cartridge filled with hollow fibers that are coated with a genetically engineered blood protein inspired by a naturally occurring human molecule called Mannose-binding lectin (MBL). MBL is found in our innate immune system and binds to toxic invaders, marking them for capture by immune cells in the spleen. Courtesy of the Wyss Institute

    But sepsis can be caused by a wide-ranging variety of pathogens that are not susceptible to antibiotics, including viruses, fungi, and parasites. What’s more, even when antibiotics successfully kill the invading bacteria, dead pathogens fragment and release toxins into the patient’s bloodstream.

    “The inflammatory cascade that leads to sepsis is triggered by pathogens, and specifically by the toxins they release,” said Wyss Institute founding director Donald Ingber, who leads the Wyss team developing the device. Ingber is the Judah Folkman Professor of Vascular Biology at Boston Children’s Hospital and Harvard Medical School and a professor of bioengineering at the Harvard John A. Paulson School of Engineering and Applied Science. “Thus, the most effective strategy is to treat with the best antibiotics you can muster, while also removing the toxins and remaining pathogens from the patient’s blood as quickly as possible.”

    The Wyss team’s blood-cleansing approach can be administered quickly, even without identifying the infectious agent. This is because it uses the Wyss Institute’s proprietary, pathogen-capturing agent, FcMBL, which binds all types of live and dead infectious microbes, including bacteria, fungi, viruses, and the toxins they release. FcMBL is a genetically engineered blood protein inspired by a naturally occurring human molecule called mannose-binding lectin (MBL), which is found in the innate immune system and binds to toxic invaders, marking them for capture by immune cells in the spleen.

    Originally, the device was conceived to operate similarly to a dialysis machine: Infected blood in an animal — and potentially one day in a patient — is flowed from one vein through catheters to the device. There, FcMBL-coated magnetic beads are added to the blood, and then bead-bound pathogens are extracted by magnets inside the device before the cleansed blood is returned to the body through another vein.

    The improved device removes the complexity, regulatory challenges, and cost associated with the magnetic beads and microfluidic architecture of its predecessor, but retains the FcMBL protein’s ability to bind to all kinds of live or dead pathogens and toxins. The optimized system uses hollow fiber filters found in dialysis cartridges already approved by the FDA whose inner walls are coated with the FcMBL protein. In animal studies, treatment with this new pathogen-extracting device reduced the number of E. coli, Staphylococcus aureus, and endotoxins circulating in the bloodstream by more than 99 percent.

    “Using the device, alone or alongside antibiotics, we can quickly bring blood back to normal conditions, curtailing an inflammatory response rather than exacerbating it,” said the paper’s first author, Tohid Fatanat Didar, a postdoctoral fellow at the Wyss institute and a research fellow at Boston Children’s Hospital. “If all goes well, physicians will someday be able to use the device in tandem with standard antibiotic treatments to deliver a one-two punch to pathogens, synergistically killing and cleansing all live and dead invaders from the bloodstream.”

    With the improved blood-cleansing therapeutic device proving extremely effective in small-animal studies, the Wyss team is planning to move to large-animal studies as the next step to demonstrating the proof of concept that is required before it can advance to human clinical trials.

    “Seeing our system work in animal models gives us confidence that this could work in humans, because we are successfully treating animals infected with human pathogens,” said Wyss senior staff scientist Michael Super, who works on the Institute’s Advanced Technology Team and is also an author on the new study.

    “Since the development of earlier prototypes of the device, we’ve applied the Wyss model of de-risking the technology to prime it for commercialization,” said Ingber. “Our goal is to see this move out of the lab and into hospitals as well as onto the battlefield, where it can save lives, within years rather than decades.”

    This work was supported by the Defense Advanced Research Projects Agency and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

    See the full article here.

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

    Please help promote STEM in your local schools.

    STEM Icon

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