News Article | March 24, 2016
Philanthropist and entrepreneur Paul G. Allen announced an initial commitment of $100 million to create The Paul G. Allen Frontiers Group, whose purpose will be to explore the landscape of bioscience and fund ideas at the frontier of knowledge to advance science and make the world better. As part of the launch, the Frontiers Group announces its first cohort of funded projects with four new Allen Distinguished Investigators (ADI) and two Allen Discovery Centers in partnership with Stanford University and Tufts University. "To make the kind of transformational advances we seek and thus shape a better future, we must invest in scientists willing to pursue what some might consider out-of-the-box approaches at the very edges of knowledge,” says Mr. Allen. “This, of course, entails a risk of setbacks and failures. But without risk, there is rarely significant reward, and unless we try truly novel approaches, we may never find the answers we seek.” The Paul G. Allen Frontiers Group, headquartered in Seattle, WA, will engage in continuous dialogue with scientists, visionaries and innovators around the world via external listening tours, workshops, symposia and major events. The group will synthesize their findings to find the untapped areas of exploration that will lead to transformational insights and achievements in science. There will be two paths for funding new ideas: Tom Skalak, Ph.D., is the founding Executive Director of The Paul G. Allen Frontiers Group. He was previously the Vice President for Research at the University of Virginia, where he conducted bioengineering research for 28 years, spanning topics from the cellular basis of microvascular adaptation to computational modeling of tissue pattern formation, and is a past-president of the American Institute of Medical and Biological Engineering and a fellow of the National Academy of Inventors. “Over the next 50 years, bioscience will undergo a radical transformation as advancements in life sciences converge with mathematics, physical sciences and engineering,” says Skalak. “The time is now to make this type of transformative investment in bioscience to advance the field and, ultimately, to make the world better.” “Paul Allen is a visionary who has proven that it’s possible to tackle scientific advancements in new ways,” says Allan Jones, Ph.D., Chief Executive Officer of the Allen Institute. “The Frontiers Group will be identifying those breakthroughs yet to come, complementing his ongoing significant investments in the Allen Institute for Brain Science and Allen Institute for Cell Science.” The Paul G. Allen Frontiers Group’s unique approach and landscape perspective are crucial to uncovering the creative ideas that span disciplines and will revolutionize scientific thinking. David Baltimore, Ph.D., Nobel Laureate, former President of Caltech, and a member of the Advisory Council of the Frontiers Group, says, “Paul Allen has a compelling long-range vision and refreshing openness to new ideas, which is essential for exploration. The Frontiers Group is cultivating a special culture of creative involvement that will encourage the larger scientific community to continuously re-invent itself, a hallmark of great science.” The Frontiers Group announces the first round of funded projects with four new Allen Distinguished Investigators and two inaugural Allen Discovery Centers. Additional Allen Discovery Centers and Allen Distinguished Investigators will be identified and named via both curation and open competitions periodically throughout a 10-year period. Allen Discovery Centers are a new type of center for leadership-driven, compass-guided research in partnership with major research organizations and universities. The Frontiers Group will typically provide $20 million over eight years with $10 million in partner leverage, for a total scope of $30 million each. The new Allen Discovery Centers are: Creating multiscale computer models that span from the inner workings of cells to the interactions between thousands of cells is a grand challenge of systems biology, and successful models are poised to have tremendous impact for researchers who study disease. The Allen Discovery Center at Stanford University will combine the expertise of computational modelers, bioengineers and bioscientists to create new models that comprehensively represent large systems of whole cells, as well as their dynamic environments and interactions. Researchers will begin by focusing on Salmonella infection of immune cells called macrophages: a system that provides insight not just into how bacteria interact with the immune system, but how drug resistance in populations of bacteria first arises. The team includes researchers at Stanford University and the University of Virginia, as well as former Google software engineers. Understanding how complex organ systems are created and repaired requires investigating the algorithms and computations performed by cell networks during pattern regulation. The Allen Discovery Center at Tufts University will seek to read, interpret and manipulate the biological code that determines anatomical structure and function during embryogenesis, regeneration and tumor suppression. A unique focus area is the processing of instructive patterning information via bioelectric signaling among cells. This work holds the potential to transform the fields of biology and medicine, as well as make crucial links in evolutionary theory and cancer biology by bridging the gap between molecular details and the larger-scale control of biological systems. The team includes researchers at Tufts University, Harvard University, Princeton University and others. The Allen Distinguished Investigator (ADI) program supports early-stage research with the potential to reinvent entire fields. Allen Distinguished Investigators are passionate thought leaders, explorers and innovators who seek world-changing breakthroughs. With grants typically between $1 million and $1.5 million each, the Frontiers Group provides these scientists with support to produce new directions in their respective fields. The new ADI recipients are: A major unsolved mystery in evolutionary developmental biology is how biological innovation happens: where do new body forms come from? Using pioneering technology known as active genetics to produce large genetic modifications, Bier will seek to uncover the design principles used in evolution to make large-scale physical changes across species. The practical applications of this work promise to guide novel synthetic biology designs that could revolutionize medicine, agriculture and care of the environment. The rise of antibiotic resistance has become a public health crisis. Collins will use principles of synthetic biology to engineer safe, frequently consumed bacteria to detect and kill dangerous bacteria, such as those that cause MRSA infections, the most frequently identified drug-resistant pathogen in United States hospitals. His novel strategy of rapidly re-designing beneficial changes in bacterial genomes could usher in a new era of design-based medicine. This frontier research will also enable scientists to understand the root causes of antibiotic resistance and the mechanisms by which traditional antibiotics work to target disease. Nature has likely evolved multiple methods of host defense, and many remain unknown. Building on her pioneering work to develop CRISPR-Cas9 gene editing technology, Doudna will look beyond the typically employed bacterial proteins to similar proteins in diverse organism and also seek out new RNA-targeting strategies. Early research shows that archaea, which can be found in extreme environments with high temperatures, have proteins similar to Cas9 but that may be capable of reaching areas of the genome currently inaccessible in CRISPR methods. Targeting RNA would offer a way to edit cell behaviors without targeting the genome directly, opening up a vast new frontier. This work has the potential to introduce novel gene editing technologies to fight human disease, improve agriculture and promote environmental health. Even though we all share fundamental neurological properties, the details of individual neural circuits can vary dramatically among individuals. Hassan has pinpointed a neural circuit in flies that serves as an ideal testing ground for understanding how molecular noise sculpts individual neural circuits during maturation and development. Unraveling the causal link between the dynamic wiring of neural circuits during development and the emergence of behavioral variability will help determine the origin of individual differences within a population, and how individual variations contribute to the fitness of the entire population. The work ultimately will shed light on what makes each of us distinct. The Paul G. Allen Frontiers Group is dedicated to exploring the landscape of science to identify and fund pioneers with ideas that will advance knowledge and make the world better. Through continuous dialogue with scientists across the world, The Paul G. Allen Frontiers Group seeks opportunities to expand the boundaries of knowledge and solve important problems. Programs include the Allen Discovery Centers at partner institutions for leadership-driven, compass-guided research, and the Allen Distinguished Investigators for frontier explorations with exceptional creativity and potential impact. The Paul G. Allen Frontiers Group was founded in 2016 by philanthropist and visionary Paul G. Allen. For more information visit allenfrontiersgroup.org. Four decades after co-founding Microsoft, entrepreneur and philanthropist Paul G. Allen is still exploring the frontiers of technology and human knowledge, and working to change the future. In 1986 he formed Vulcan, his private company which oversees all his philanthropic and business activities including but not limited to Vulcan Aerospace, Vulcan Capital, Vulcan Real Estate, Vulcan Productions, Vulcan Philanthropy, the Paul G. Allen Family Foundation, as well as sports teams, research institutes, museums and arts and entertainment venues. In all his endeavors, Mr. Allen constantly asks “What if…?” and pushes people to challenge conventional thinking, collaborate across disciplines and reimagine what’s possible. With a lifetime personal giving totaling over $2 billion, Mr. Allen is dedicated to tackling some of the world’s biggest challenges through his philanthropic initiatives and business ventures. Mr. Allen is deeply invested locally in his hometown of Seattle and the Pacific Northwest, while taking measured steps resulting in global impact. Mr. Allen is passionate about exploring new frontiers, fueling discovery and experimenting on multiple fronts. To learn more, visit PaulAllen.com. The Allen Institute is an independent, 501(c)(3) nonprofit research organization founded by philanthropist and visionary Paul G. Allen. The Allen Institute is dedicated to answering some of the biggest questions in bioscience and accelerating research worldwide. The Institute is a recognized leader in large-scale research with a commitment to an open science model within its research institutes, the Allen Institute for Brain Science, launched in 2003, and the Allen Institute for Cell Science, launched in 2014. In 2016, the Allen Institute expanded its reach toward the broader landscape of bioscience with the launch of The Paul G. Allen Frontiers Group, which identifies pioneers with new ideas to expand the boundaries of knowledge and make the world better. For more information, visit alleninstitute.org.
Abdelgaied A.,Institute of Medical and Biological Engineering |
Stanley M.,Institute of Medical and Biological Engineering |
Galfe M.,Tissue Regenix |
Berry H.,Tissue Regenix |
And 2 more authors.
Journal of Biomechanics | Year: 2015
Meniscal repair is widely used as a treatment for meniscus injury. However, where meniscal damage has progressed such that repair is not possible, approaches for partial meniscus replacement are now being developed which have the potential to restore the functional role of the meniscus, in stabilising the knee joint, absorbing and distributing stress during loading, and prevent early degenerative joint disease. One attractive potential solution to the current lack of meniscal replacements is the use of decellularised natural biological scaffolds, derived from xenogeneic tissues, which are produced by treating the native tissue to remove the immunogenic cells. The current study investigated the effect of decellularisation on the biomechanical tensile and compressive (indentation and unconfined) properties of the porcine medial meniscus through an experimental-computational approach. The results showed that decellularised medial porcine meniscus maintained the tensile biomechanical properties of the native meniscus, but had lower tensile initial elastic modulus. In compression, decellularised medial porcine meniscus generally showed lower elastic modulus and higher permeability compared to that of the native meniscus. These changes in the biomechanical properties, which ranged from less than 1% to 40%, may be due to the reduction of glycosaminoglycans (GAG) content during the decellularisation process. The predicted biomechanical properties for the decellularised medial porcine meniscus were within the reported range for the human meniscus, making it an appropriate biological scaffold for consideration as a partial meniscus replacement. © 2015 The Authors.
PubMed | University of Leeds, Institute of Medical and Biological Engineering and Tissue Regenix
Type: Comparative Study | Journal: Journal of biomechanics | Year: 2015
Meniscal repair is widely used as a treatment for meniscus injury. However, where meniscal damage has progressed such that repair is not possible, approaches for partial meniscus replacement are now being developed which have the potential to restore the functional role of the meniscus, in stabilising the knee joint, absorbing and distributing stress during loading, and prevent early degenerative joint disease. One attractive potential solution to the current lack of meniscal replacements is the use of decellularised natural biological scaffolds, derived from xenogeneic tissues, which are produced by treating the native tissue to remove the immunogenic cells. The current study investigated the effect of decellularisation on the biomechanical tensile and compressive (indentation and unconfined) properties of the porcine medial meniscus through an experimental-computational approach. The results showed that decellularised medial porcine meniscus maintained the tensile biomechanical properties of the native meniscus, but had lower tensile initial elastic modulus. In compression, decellularised medial porcine meniscus generally showed lower elastic modulus and higher permeability compared to that of the native meniscus. These changes in the biomechanical properties, which ranged from less than 1% to 40%, may be due to the reduction of glycosaminoglycans (GAG) content during the decellularisation process. The predicted biomechanical properties for the decellularised medial porcine meniscus were within the reported range for the human meniscus, making it an appropriate biological scaffold for consideration as a partial meniscus replacement.
Suner S.,Lulea University of Technology |
Bladen C.L.,Institute of Medical and Biological Engineering |
Gowland N.,Institute of Medical and Biological Engineering |
Tipper J.L.,Institute of Medical and Biological Engineering |
Emami N.,Lulea University of Technology
Wear | Year: 2014
Ultra high molecular weight polyethylene (UHMWPE) has been extensively used as a bearing surface in joint prostheses. However, wear debris generated from this material has been associated with osteolysis and implant loosening. Alternative materials, such as polymer composites, have been investigated due to their exceptional mechanical properties. The goal of the present work was to investigate the wear rate, size and volume distributions, bioactivity and biocompatibility of the wear debris generated from a UHMWPE/Multi-walled carbon nanotube (MWCNT) nanocomposite material compared with conventional UHMWPE. The results showed that the addition of MWCNTs led to a significant reduction in wear rate. Specific biological activity and functional biological activity predictions showed that wear particles from the UHMWPE/MWCNT nanocomposite had a reduced osteolytic potential compared to those produced from the conventional polyethylene. In addition, clinically relevant UHMWPE/MWCNT wear particles did not show any adverse effects on the L929 fibroblast cell viability at any of the concentrations tested over time. These findings suggest that UHMWPE/MWCNT nanocomposites represent an attractive alternative for orthopaedic applications. © 2014 Elsevier B.V.
Suner S.,Lulea University of Technology |
Joffe R.,Lulea University of Technology |
Tipper J.L.,Institute of Medical and Biological Engineering |
Emami N.,Lulea University of Technology
Composites Part B: Engineering | Year: 2015
Numerous carbon nanostructures have been investigated in the last years due to their excellent mechanical properties. In this work, the effect of the addition of graphene oxide (GO) nanoparticles to UHMWPE and the optimal %wt GO addition were investigated. UHMWPE/GO nanocomposites with different GO wt% contents were prepared and their mechanical, thermal, structural and wettability properties were investigated and compared with virgin UHMWPE. The results showed that the thermal stability, oxidative resistance, mechanical properties and wettability properties of UHMWPE were enhanced due to the addition of GO. UHMWPE/GO materials prepared with up to 0.5 wt% GO exhibited improved characteristics compared to virgin UHMWPE and nanocomposites prepared with higher GO contents. © 2015 Elsevier Ltd. All rights reserved.
News Article | December 1, 2016
Polymerization by chemical vapor deposition (CVD) is a simple method for modifying surfaces by which topologically challenging substrates can be evenly coated with polymers. In the journal Angewandte Chemie, researchers have now introduced the first CVD method for producing degradable polymers. Biomolecules or drugs can be attached by means of special side groups. This introduces new possibilities for applications like the coating of biodegradable implants. In CVD polymerization, the starting compounds are vaporized, activated at high temperature, and deposited onto surfaces, where they polymerize. In medical applications, substrates for implants are coated to allow functional groups to be added as anchors for the attachment of biomolecules or drugs. Until now, however, it has only been possible to coat nondegradable implants, not materials that need to degrade after fulfilling their task, like surgical sutures, systems for controlled drug delivery, drug-eluding stents, or tissue engineering scaffolds. This is because it was previously not possible to make degradable coatings by CVD. Scientists from the University of Michigan (Ann Arbor, USA), Northwestern Polytechnical University (Xi'an, China), and the Karlsruhe Institute of Technology (KIT, Eggenstein-Leopoldshafen, Germany) have now synthesized the first CVD polymer with a degradable backbone. The research team led by Jörg Lahann succeeded by using two special types of monomer: The paracyclophanes usually used for this process were combined with cyclic ketene acetals. While the classic polymers based on paracyclophanes are connected exclusively through carbon-carbon bonds, the ketene acetal converts during the polymerization so that ester bonds (a bond between a carbon and an oxygen atom) are formed within the polymer backbone. Ester bonds can be broken in aqueous environments. "The speed of the degradation depends on the ratio of the two types of monomer as well as their side chains," explains Lahann. "Polar side chains make the polymer film less hydrophobic and accelerate degradation because water can penetrate more easily. The speed of degradation can thus be tailored to the intended use." Tests with cell cultures demonstrated that neither the polymer nor its degradation products are toxic. The team produced polymer films that were equipped with functional side groups that act as "anchor points" for molecules, which can be used to attach fluorescence dyes and biomolecules. "Our new degradable polymer films could find broad application for the functionalization and coating of surfaces in the biological sciences as well as medicine and for food packaging applications," states Lahann. Dr. Lahann is Professor of Chemical Engineering, Materials Science and Engineering and Biomedical Engineering at the University of Michigan. He also serves as the Director of the Biointerfaces Institute at the University of Michigan and the Co-Director of the Institute for Functional Interfaces at the Karlrsruhe Institute of Technology, Germany. He has been selected byTechnology Review as one of the top 100 young innovators and is the recipient of the 2007 Nanoscale Science and Engineering Award as well as a NSF-CAREER award. Since 2011, he has been a fellow of the American Institute of Medical and Biological Engineering.
Joo S.,University of Ulsan |
Kim K.H.,Interdisciplinary Program |
Kim H.C.,Institute of Medical and Biological Engineering |
Chung T.D.,Seoul National University
Biosensors and Bioelectronics | Year: 2010
A portable microfluidic flow cytometer with dual detection ability of impedance and fluorescence was developed for cell analysis and particle-based assays. In the proposed system, fluorescence from microparticles and cells is measured through excitation by a light emitting diode (LED) and detection by a solid-stated photomultiplier (SSPM). Simultaneous impedometric detection provides information on the existence and size of microparticles and cells through polyelectrolyte gel electrodes (PGEs) operated by custom designed circuits for signal detection, amplification, and conversion. Fluorescence and impedance signals were sampled at 1 kHz with 12 bit resolution. The resulting microfluidic cytometer is 15 × 10 × 10 cm3 in width, depth, and height, with a weight of about 800 g. Such a miniaturized and battery powered system yielded a portable microfluidic cytometer with high performance. Various microbeads and human embryonic kidney 293 (HEK-293) cells were employed to evaluate the system. Impedance and fluorescence signals from each bead or cell made classification of micro particles or cells easy and fast. © 2009 Elsevier B.V. All rights reserved.
Han D.,Seoul National University |
Han D.,Institute of Medical and Biological Engineering |
Moon S.,Seoul National University |
Kim Y.,Seoul National University |
And 6 more authors.
Journal of Proteome Research | Year: 2012
Type 2 diabetes results from aberrant regulation of the phosphorylation cascade in beta-cells. Phosphorylation in pancreatic beta-cells has not been examined extensively, except with regard to subcellular phosphoproteomes using mitochondria. Thus, robust, comprehensive analytical strategies are needed to characterize the many phosphorylated proteins that exist, because of their low abundance, the low stoichiometry of phosphorylation, and the dynamic regulation of phosphoproteins. In this study, we attempted to generate data on a large-scale phosphoproteome from the INS-1 rat pancreatic beta-cell line using linear ion trap MS/MS. To profile the phosphoproteome in-depth, we used comprehensive phosphoproteomic strategies, including detergent-based protein extraction (SDS and SDC), differential sample preparation (in-gel, in-solution digestion, and FASP), TiO 2 enrichment, and MS replicate analyses (MS2-only and multiple-stage activation). All spectra were processed and validated by stringent multiple filtering using target and decoy databases. We identified 2467 distinct phosphorylation sites on 1419 phosphoproteins using 4 mg of INS-1 cell lysate in 24 LC-MS/MS runs, of which 683 (27.7%) were considered novel phosphorylation sites that have not been characterized in human, mouse, or rat homologues. Our informatics data constitute a rich bioinformatics resource for investigating the function of reversible phosphorylation in pancreatic beta-cells. In particular, novel phosphorylation sites on proteins that mediate the pathology of type 2 diabetes, such as Pdx-1, Nkx.2, and Srebf1, will be valuable targets in ongoing phosphoproteomics studies. © 2012 American Chemical Society.
Yoon C.,Seoul National University |
Lee J.,Seoul National University |
Kim K.,Seoul National University |
Kim H.C.,Institute of Medical and Biological Engineering |
Chung S.G.,Seoul National University
PM and R | Year: 2015
Objective: To develop a simple method of quantifying dynamic lumbar stability by evaluating postural changes of the lumbar spine during a wall plank-and-roll (WPR) activity while maintaining maximal trunk rigidity. Design: A descriptive, exploratory research with a convenience sample. Setting: A biomechanics laboratory of a tertiary university hospital. Participants: Sixteen healthy young subjects (8 men and 8 women; 30.7 ± 6.8 years old) and 3 patients (2 men 46 and 50 years old; 1 woman 54 years old) with low back pain (LBP). Methods: The subjects performed the WPR activity with 2 inertial sensors attached on the thoracic spine and sacrum. Relative angles between the sensors were calculated to characterize lumbar posture in 3 anatomical planes: axial twist (AT), kyphosis-lordosis (KL), or lateral bending (LB). Isokinetic truncal flexion and extension power were measured. Main Outcome Measures: AT, KL, and LB were compared between the initial plank and maximal roll positions. Angular excursions were compared between males and females and between rolling sides, and tested for correlation with isokinetic truncal muscle power. Patterns and consistencies of the lumbar postural changes were determined. Lumbar postural changes of each patient were examined in the aspects of pattern and excursion, considering those from the healthy subjects as reference. Results: AT, KL, and LB were significantly changed from the initial plank to the maximal roll position (P < .01); that is, the thoracic spine rotated further, lumbar lordosis increased, and the thoracic spine was bent away from the wall by 6.9° ± 12.0°, 9.5° ± 6.5°, and 7.9° ± 4.9°, respectively. The patterns and amounts of lumbar postural changes were not significantly different between the rolling sides or between male and female participants, except that the excursion in AT was larger on the dominant rolling side. The excursions were not related to isokinetic truncal muscle power. The 3 LBP patients showed varied deviations in pattern and excursion from the average of the healthy subjects. Conclusions: Certain amounts and patterns of lumbar postural changes were observed in healthy young subjects, with no significant variations based on gender, rolling side, or truncal muscle power. Application of the evaluation on LBP patients revealed prominent deviations from the healthy postural changes, suggesting potential clinical applicability. Therefore, with appropriate development and case stratification, we believe that the quantification of lumbar postural changes during WPR activity can be used to assess dynamic lumbar stability in clinical practice. © 2015 American Academy of Physical Medicine and Rehabilitation.
Liu A.,Institute of Medical and Biological Engineering |
Ingham E.,University of Leeds |
Fisher J.,Institute of Medical and Biological Engineering |
Tipper J.L.,Institute of Medical and Biological Engineering
Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine | Year: 2014
It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both singlestation and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different poresized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 mm pore sizes allowed successful isolation of ultra-high-molecular- weight polyethylene wear particles with a size range of \100 nm, which was suitable for cell culture studies.© IMechE 2014.