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  • richardmitnick 1:49 pm on August 8, 2018 Permalink | Reply
    Tags: , Biology, , Maping Cancer Markets project takes on sarcoma, ,   

    From World Community Grid (WCG): “Sarcoma Dataset Coming Soon to Mapping Cancer Markers Project” 

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    From World Community Grid (WCG)

    8 Aug 2018
    Dr. Igor Jurisica

    In this comprehensive update, the Mapping Cancer Markers team explains how they are determining which genes and gene signatures carry the greatest promise for lung cancer diagnosis. They also introduce the next type of cancer–sarcoma–to be added soon to the project.

    The Mapping Cancer Markers (MCM) project continues to process work units for the ovarian cancer dataset. As we accumulate these outcomes, we continue to analyze MCM results from the lung cancer dataset. In this update, we discuss preliminary findings from this analysis. In addition, we introduce the sarcoma dataset that will be our focus in the next stage.

    Patterns of gene-family biomarkers in lung cancer

    In cancer, and human biology in general, multiple groups of biomarkers (genes, protein, microRNAs, etc.) can have similar patterns of activity and thus clinical utility, helping diagnosis, prognosis or predicting treatment outcome. For each cancer subtype, one could find large number of such groups of biomarkers, each having similar predictive power; yet current statistical and AI-based methods identify only one from a given data set.

    We have two primary goals in MCM: 1) to find good groups of biomarkers for the cancers we study, and 2) to identify how and why these biomarkers form useful groups, so we can build a heuristic approach that will find such groups for any disease without needing months of computation on World Community Grid. The first goal will give us not only information that after validation may be useful in clinical practice, but importantly, it will generate data that we will use to validate our heuristics.

    1
    Illustration 1: Proteins group by similar interactions and similar biological functions.

    Multiple groups of biomarkers exist primarily due to the redundancy and complex wiring of the biological system. For example, the highly interconnected human protein-protein interaction network enables us to see how individual proteins perform diverse molecular functions and together contribute to a specific biological process, as shown above in Illustration 1. Many of these interactions change between healthy and disease states, which in turn affects the functions these proteins carry. Through these analyses, we aim to build models of these processes that in turn could be used to design new therapeutic approaches.

    Two specific groups of biomarkers may appear different from each other, yet perform equivalently because the proteins perform similar molecular functions. However, using these groups of biomarkers for patient stratification may not be straightforward. Groups of biomarkers often do not validate in new patient cohorts or when measured by different biological assays, and there are thousands of possible combinations to consider. Some groups of biomarkers may have all reagents available while others may need to be develop (or be more expensive); they may also have different robustness, sensitivity and accuracy, affecting their potential as clinically useful biomarkers.

    At the present time, there is no effective approach to find all good groups of biomarkers necessary to achieve the defined goal, such as accurately predicting patient risk or response to treatment.

    The first goal of the Mapping Cancer Markers project is to gain a deeper understanding of the “rules” of why and how proteins interact and can be combined to form a group of biomarkers, which is essential to understanding their role and applicability. Therefore, we are using the unique computational resource of World Community Grid to systematically survey the landscape of useful groups of biomarkers for multiple cancers and purposes (diagnosis and prognosis). Thereby, we established a benchmark for cancer gene biomarker identification and validation. Simultaneously, we are applying unsupervised learning methods such as hierarchical clustering to proteins that group by predictive power and biological function.

    The combination of this clustering and the World Community Grid patterns enables us to identify generalized gene clusters that provide deeper insights to the molecular background of cancers, and give rise to more reliable groups of gene biomarkers for cancer detection and prognosis.

    Currently, we are focusing on the first-phase results from the lung cancer dataset, which focused on a systematic exploration of the entire space of potential fixed-length groups of biomarkers.

    3
    Illustration 2: Workflow of the MCM-gene-pattern-family search. The results of the World Community Grid analysis combined with the unsupervised clustering of genes identifies a set of gene-pattern-families, generalizing the groups of biomarkers. Finally, the results are evaluated using known cancer biomarkers and by using functional annotations, such as signaling pathways, gene ontology function and processes.

    As depicted above in Illustration 2, World Community Grid computed about 10 billion randomly selected groups of biomarkers, to help us understand the distribution of which group sizes and biomarker combinations perform well, which in turn we will use to validate heuristic approaches. Analysis showed that about 45 million groups of biomarkers had a high predictive power and passed the quality threshold. This evaluation gives us a detailed and systematic picture of which genes and gene groups carry the most valuable information for lung cancer diagnosis. Adding pathway and protein interaction network data enables us to further interpret and fathom how and why these groups of biomarkers perform well, and what processes and functions these proteins carry.

    Simultaneously, we used the described lung cancer data to discover groups of similar genes. We assume that these genes or the encoded proteins fulfill similar biological functions or are involved in the same molecular processes.

    3
    Illustration 3: Evaluation of the hierarchical clustering of the lung cancer data, using the complete linkage parameter, for different numbers of groups indicated by the K-values (100 to 1000). The first plot shows the silhouette value – a quality metric in this clustering, i.e., measure of how well each object relates to its cluster compared to other clusters. The second plot depicts the inter- and intra-cluster distance and the ratio of intra/inter cluster distance.

    To find the appropriate clustering algorithms and the right number of gene groups (clusters) we use different measures to evaluate the quality of each of the individual clustering. For instance, Illustration 3 (above) shows the results of the evaluation of the hierarchical clustering for different numbers of clusters. To evaluate clustering quality, we used silhouette value (method for assessing consistency within clusters of data, i.e., measure of how well each object relates to its own cluster compared to other clusters). A high silhouette value indicates good clustering configuration, and the figure shows a large increase in the silhouette value at 700 gene groups. Since this indicates a significant increase in quality, we subsequently select this clustering for further analysis.

    Not all combinations of biological functions or the lack of it will lead to cancer development and will be biologically important. In the next step, we apply a statistical search to investigate which combinations of clusters are most common among the well-preforming biomarkers, and therefore result in gene groups or pattern families. Since some gene-pattern-families are likely to occur even at random, we use enrichment analysis to ensure the selection only contains families that occur significantly more often than random.

    In the subsequent step we validated the selected generalized gene-pattern-families using an independent set of 28 lung cancer data sets. Each of these studies report one or several groups of biomarkers of up- or down-regulated genes that are indicative for lung cancer.


    Illustration 4: Shown is a selection of high performing pattern families and how they are supported by 28 previously published gene signatures. Each circle in the figure indicates the strength of the support: The size of the circle represents the number of clusters in the family that where found significantly more often in the signature of this study. The color of the circle indicates the average significance calculated for all clusters in the pattern-family.

    5
    Illustration 5: One of the most frequent gene-pattern-families, is a combination of cluster 1, 7 and 21. We annotated each cluster with pathways using pathDIP and visualized it using word clouds (the larger the word/phrase, the most frequently it occurs).

    The word cloud visualization indicates that cluster 7 is involved in pathways related to GPCRs (G protein–coupled receptor) and NHRs (nuclear hormone receptors). In contrast, the genes in cluster 1 are highly enriched in EGFR1 (epidermal growth factor receptor) as well as translational regulation pathways. Mutations affecting the expression of EGFR1, a transmembrane protein, have shown to result in different types of cancer, and in particular lung cancer (as we have shown earlier, e.g., (Petschnigg et al., J Mol Biol 2017; Petschnigg et al., Nat Methods 2014)). The aberrations increase the kinase activity of EGFR1, leading to hyperactivation of downstream pro-survival signaling pathways and a subsequent uncontrolled cell division. The discovery of EGFR1 initiated the development of therapeutic approaches against various cancer types including lung cancer. The third group of genes are common targets of microRNAs. Cluster 21 indicates strong involvement with microRNAs, as we and others have shown before (Tokar et al., Oncotarget 2018; Becker-Santos et al., J Pathology, 2016; Cinegaglia et al., Oncotarget 2016).

    6
    Illustration 6: Evaluation of enriched pathways for cluster 1. Here we used our publicly available pathway enrichment analysis portal pathDIP (Rahmati et al., NAR 2017). The network was generated with our network visualization and analysis tool NAViGaTOR 3 (http://ophid.utoronto.ca/navigator).

    The final illustration evaluates the 20 most significantly enriched pathways for cluster 1. The size of the pathway nodes corresponds to the number of involved genes, and the width of the edges corresponds the number genes of overlapping between pathways. One can see that all pathways involved in translation are highly overlapping. mRNA-related pathways form another highly connected component in the graph. The EGFR1 pathway is strongly overlapping with many of the other pathways, indicating that genes that are affected by those pathways are involved in a similar molecular mechanism.

    Sarcoma

    After lung and ovarian cancers, next we will focus on sarcoma. Sarcomas are a heterogeneous group of malignant tumors that are relatively rare. They are typically categorized according to the morphology and type of connective tissues that they arise in, including fat, muscle, blood vessels, deep skin tissues, nerves, bones and cartilage, which comprises less than 10% of all malignancies (Jain 2010). Sarcomas can occur anywhere in the human body, from head to foot, can develop in patients of any age including children, and often vary in aggressiveness, even within the same organ or tissue subtype (Honore 2015). This suggests that a histological description by organ and tissue type is neither sufficient for categorization of the disease nor does it help in selecting the most optimal treatment.

    Diagnosing sarcomas poses a particular dilemma, not only due to their rarity, but also due to their diversity, with more than 70 histological subtypes, and our insufficient understanding of the molecular characteristics of these subtypes (Jain 2010).

    Therefore, recent research studies focused on molecular classifications of sarcomas based on genetic alterations, such as fusion genes or oncogenic mutations. While research achieved major developments in local control/limb salvage, the survival rate for “high-risk” soft tissue sarcomas (STSs) has not improved significantly, especially in patients with a large, deep, high-grade sarcoma (stage III) (Kane III 2018).

    For these reasons, in the next phase of World Community Grid analysis, we will focus on the evaluation of the genomic background of sarcoma. We will utilize different sequencing information and technologies to gain a broader knowledge between the different levels of genetic aberrations and the regulational implications. We will provide a more detailed description of the data and the incentives in the next update.

    Petschnigg J, Kotlyar M, Blair L, Jurisica I, Stagljar I, and Ketteler R, Systematic identification of oncogenic EGFR interaction partners, J Mol Biol, 429(2): 280-294, 2017.
    Petschnigg, J., Groisman, B., Kotlyar, M., Taipale, M., Zheng, Y., Kurat, C., Sayad, A., Sierra, J., Mattiazzi Usaj, M., Snider, J., Nachman, A., Krykbaeva, I., Tsao, M.S., Moffat, J., Pawson, T., Lindquist, S., Jurisica, I., Stagljar, I. Mammalian Membrane Two-Hybrid assay (MaMTH): a novel split-ubiquitin two-hybrid tool for functional investigation of signaling pathways in human cells; Nat Methods, 11(5):585-92, 2014.
    Rahmati, S., Abovsky, M., Pastrello, C., Jurisica, I. pathDIP: An annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis. Nucl Acids Res, 45(D1): D419-D426, 2017.
    Kane, John M., et al. “Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.” Sarcoma 2018 (2018).
    Jain, Shilpa, et al. “Molecular classification of soft tissue sarcomas and its clinical applications.” International journal of clinical and experimental pathology 3.4 (2010): 416.
    Honore, C., et al. “Soft tissue sarcoma in France in 2015: epidemiology, classification and organization of clinical care.” Journal of visceral surgery 152.4 (2015): 223-230.
    Tokar T, Pastrello C, Ramnarine VR, Zhu CQ, Craddock KJ, Pikor L, Vucic EA, Vary S, Shepherd FA, Tsao MS, Lam WL, Jurisica Differentially expressed microRNAs in lung adenocarcinoma invert effects of copy number aberrations of prognostic genes. Oncotarget. 9(10):9137-9155, 2018
    Becker-Santos, D.D., Thu, K.L, English, J.C., Pikor, L.A., Chari, R., Lonergan, K.M., Martinez, V.D., Zhang, M., Vucic, E.A., Luk, M.T.Y., Carraro, A., Korbelik, J., Piga, D., Lhomme, N.M., Tsay, M.J., Yee, J., MacAulay, C.E., Lockwood, W.W., Robinson, W.P., Jurisica, I., Lam, W.L., Developmental transcription factor NFIB is a putative target of oncofetal miRNAs and is associated with tumour aggressiveness in lung adenocarcinoma, J Pathology, 240(2):161-72, 2016.
    Cinegaglia, N.C., Andrade, S.C.S., Tokar, T., Pinheiro, M., Severino, F. E., Oliveira, R. A., Hasimoto, E. N., Cataneo, D. C., Cataneo, A.J.M., Defaveri, J., Souza, C.P., Marques, M.M.C, Carvalho, R. F., Coutinho, L.L., Gross, J.L., Rogatto, S.R., Lam, W.L., Jurisica, I., Reis, P.P. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung, adenocarcinoma, Oncotarget, 7(20): 28920-34, 2016.

    Other news

    We have secured a major funding from Ontario Government for our research: The Next Generation Signalling Biology Platform. The main goal of the project is developing novel integrated analytical platform and workflow for precision medicine. This project will create an internationally accessible resource that unifies different types of biological data, including personal health information—unlocking its full potential and making it more usable for research across the health continuum: from genes and proteins to pathways, drugs and humans.

    We have also published papers describing several tools, portals and applications with our collaborators. Below we list those most related directly or indirectly to work on World Community Grid:

    Wong, S., Pastrello, C., Kotlyar, M., Faloutsos, C., Jurisica, I. SDREGION: Fast spotting of changing communities in biological networks. ACM KDD Proceedings, 2018. In press. BMC Cancer, 18(1):408, 2018.
    Kotlyar, M., Pastrello, C., Rossos, A., Jurisica, I. Protein-protein interaction databases. Eds. Cannataro, M. et al. Encyclopedia of Bioinformatics and Computational Biology, 81, Elsevier. In press. doi.org/10.1016/B978-0-12-811414-8.20495-1
    Rahmati, S., Pastrello, C., Rossos, A., Jurisica, I. Two Decades of Biological Pathway Databases: Results and Challenges, Eds. Cannataro, M. et al. Encyclopedia of Bioinformatics and Computational Biology, 81, Elsevier. In press.
    Hauschild, AC, Pastrello, C., Rossos, A., Jurisica, I. Visualization of Biomedical Networks, Eds. Cannataro, M. et al. Encyclopedia of Bioinformatics and Computational Biology, 81, Elsevier. In press.
    Sivade Dumousseau M, Alonso-López D, Ammari M, Bradley G, Campbell NH, Ceol A, Cesareni G, Combe C, De Las Rivas J, Del-Toro N, Heimbach J, Hermjakob H, Jurisica I, Koch M, Licata L, Lovering RC, Lynn DJ, Meldal BHM, Micklem G, Panni S, Porras P, Ricard-Blum S, Roechert B, Salwinski L, Shrivastava A, Sullivan J, Thierry-Mieg N, Yehudi Y, Van Roey K, Orchard S. Encompassing new use cases – level 3.0 of the HUPO-PSI format for molecular interactions. BMC Bioinformatics, 19(1):134, 2018.
    Minatel BC, Martinez VD, Ng KW, Sage AP, Tokar T, Marshall EA, Anderson C, Enfield KSS, Stewart GL, Reis PP, Jurisica I, Lam WL., Large-scale discovery of previously undetected microRNAs specific to human liver. Hum Genomics, 12(1):16, 2018.
    Tokar T, Pastrello C, Ramnarine VR, Zhu CQ, Craddock KJ, Pikor L, Vucic EA, Vary S, Shepherd FA, Tsao MS, Lam WL, Jurisica, I. Differentially expressed microRNAs in lung adenocarcinoma invert effects of copy number aberrations of prognostic genes. Oncotarget. 9(10):9137-9155, 2018.
    Paulitti A, Corallo D, Andreuzzi E, Bizzotto D, Marastoni S, Pellicani R, Tarticchio G, Pastrello C, Jurisica I, Ligresti G, Bucciotti F, Doliana R, Colladel R, Braghetta P, Di Silvestre A, Bressan G, Colombatti A, Bonaldo P, Mongiat M. Matricellular EMILIN2 protein ablation ca 1 uses defective vascularization due to impaired EGFR-dependent IL-8 production, Oncogene, Feb 27. doi: 10.1038/s41388-017-0107-x. [Epub ahead of print] 2018.
    Tokar, T., Pastrello, C., Rossos, A., Abovsky, M., Hauschild, A.C., Tsay, M., Lu, R., Jurisica. I. mirDIP 4.1 – Integrative database of human microRNA target predictions, Nucl Acids Res, D1(46): D360-D370, 2018.
    Kotlyar M., Pastrello, C., Rossos, A., Jurisica, I., Prediction of protein-protein interactions, Current Protocols in Bioinf, 60, 8.2.1–8.2.14., 2017.
    Singh, M., Venugopal, C., Tokar, T., Brown, K.B., McFarlane, N., Bakhshinyan, D., Vijayakumar, T., Manoranjan, B., Mahendram, S., Vora, P., Qazi, M., Dhillon, M., Tong, A., Durrer, K., Murty, N., Hallet, R., Hassell, J.A., Kaplan, D., Jurisica, I., Cutz, J-C., Moffat, J., Singh, D.K., RNAi screen identifies essential regulators of human brain metastasis initiating cells, Acta Neuropathologica, 134(6):923-940, 2017.

    Thank you.

    This work would not be possible without the participation of World Community Grid Members. Thank you for generously contributing CPU cycles, and for your interest in this and other World Community Grid projects.

    See the full article here.


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  • richardmitnick 8:47 am on August 6, 2018 Permalink | Reply
    Tags: , , Bio-inspired design and assembly, Biology, , ,   

    From University of Washington: “UW, PNNL to host energy research center focusing on bio-inspired design and assembly” 

    U Washington

    From University of Washington

    August 3, 2018
    James Urton

    The United States Department of Energy has awarded an expected $10.75 million, four-year grant to the University of Washington, the Pacific Northwest National Laboratory and other partner institutions for a new interdisciplinary research center to define the enigmatic rules that govern how molecular-scale building blocks assemble into ordered structures — and give rise to complex hierarchical materials.


    PNNL

    The Center for the Science of Synthesis Across Scales, or CSSAS, will bring together researchers from biology, engineering and the physical sciences to uncover new insights into how molecular interactions control assembly and apply these principles toward creating new materials with novel and revolutionary properties for applications in energy technology.

    “This center seeks to understand the fundamental rules of how order emerges from the interaction of simple building blocks,” said CSSAS Director François Baneyx, the Matthaei Professor and Chair of the UW Department of Chemical Engineering. “What are the energetics, rates and pathways involved, and what properties emerge when simple components come together in increasingly complex layers? Those are some of our driving questions.”

    The UW-based CSSAS is among the newest members of the Energy Frontier Research Centers announced June 29 by the Department of Energy. These centers, operated out of universities and national labs, are funded by the Department of Energy and devoted to specific goals in energy science. The work at the CSSAS will focus on understanding the principles of “hierarchical synthesis” — the process by which molecules come together, bind, interact and create layer upon layer of higher-ordered structures.

    2
    The initial stage of the assembly of protein building blocks (left) and a self-assembled peptoid sheet (right). Scale bars indicate length in nanometers.Jim De Yoreo/Chun-Long Chen

    CSSAS experiments will focus on protein-based building blocks, but will also probe protein-like synthetic compounds called peptoids as well as inorganic nanoparticles. Studying the biologically inspired assembly of these systems individually and in combination will shed new light on how living organisms, through billions of years of adaptation and evolution, have created complex hierarchical systems to solve a host of challenges, said Baneyx.

    Understanding hierarchical synthesis would allow engineers to design and build new materials with unique properties for innovative technological advancements that can come about only when scientists exert precise control over a material. For example, controlling how charges move precisely through a material — or how a substrate is shuttled between the active sites of a series of enzymes positioned with nanoscale precision — could be key to creating new materials for energy storage, transmission and generation. The precision control that scientists envision could also yield functional materials that are self-healing or self-repairing, and have other custom physical properties designed within them.

    “Scientists have been trying to create these types of innovative materials largely through ‘top-down’ approaches, and often by reverse engineering an interesting biological material,” said Baneyx. “We will begin with the blocks themselves, exploring how order evolves in the synthesis process when the blocks are put together and interact.”

    CSSAS research will focus on three major areas:

    Investigating the emergence of order from the interactions of individual building blocks, be they peptoids, inorganic nanoparticles or protein-based particles
    Probing how hierarchy unfolds as these building blocks are combined to construct lattices, active structures and hybrid materials
    Using machine learning, computational simulations and big data analytics to learn new ways to control the assembly dynamics of hierarchical structures

    3
    No image caption or credit

    These investigations will build upon work conducted at the UW Institute for Protein Design, led by UW biochemistry professor and Howard Hughes Medical Institute investigator David Baker, and harness the expertise of researchers at the University of Chicago, the Oak Ridge National Laboratory and the University of California, San Diego.


    Dr. David Baker, Baker Lab, U Washington


    David Baker’s Rosetta@home project, a project running on BOINC software from UC Berkeley


    Rosetta@home BOINC project



    The CSSAS effort was enabled by the Northwest Institute for Materials Physics, Chemistry, and Technology, or NW IMPACT, which was formally launched earlier this year by UW President Ana Mari Cauce and PNNL Director Steven Ashby to fertilize cross-disciplinary collaborations between UW and PNNL researchers. NW IMPACT co-director Jim De Yoreo, who is the PNNL chief scientist for materials synthesis and simulation across scales and also holds a joint appointment at the UW in both chemistry and materials science and engineering, will serve as the deputy director of the CSSAS.

    “This center’s focus is ultimately on unlocking potential,” said Baneyx. “Once we understand the fundamental rules governing the assembly of bioinspired building blocks, we will be able to design new materials to meet a broad range of technological needs.”

    For more information, contact Baneyx at 206-685-7659 or baneyx@uw.edu and De Yoreo at 509-375-6494 or james.deyoreo@pnnl.gov.

    See the full article here .


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    Please help promote STEM in your local schools.

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
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  • richardmitnick 10:00 am on August 2, 2018 Permalink | Reply
    Tags: , Biology, Professor Selman Waksman, , Streptomyces griseus,   

    From Rutgers University: “Rutgers Discovery That Changed the World May Become New Jersey’s State Microbe” 

    Rutgers smaller
    Our Great Seal.

    From Rutgers University

    Todd Bates
    848-932-0550
    todd.bates@rutgers.edu

    1
    A color-enhanced photo of Streptomyces griseus, a soil-based bacterium. Image: John Warhol and Actinomycetes Society of Japan.

    A soil-based bacterium called Streptomyces griseus could become New Jersey’s official state microbe 75 years after Rutgers University–New Brunswick scientists discovered its ability to cure tuberculosis.

    The 1943 discovery at the New Jersey Agricultural Experiment Station defined Rutgers’ role as a leader in antibiotic research and had a profound impact on global health. Professor Selman Waksman and graduate students Albert Schatz and Elizabeth Bugie found that S. griseus produces an antibiotic, which they named streptomycin, that kills the bacteria that cause tuberculosis, cholera, typhoid and dysentery, all of which were resistant to penicillin. Waksman was awarded the 1952 Nobel Prize in Physiology or Medicine and is the namesake of Rutgers’ Waksman Institute of Microbiology.

    The New Jersey State Senate last week voted 33-0 to approve a bill that would name S. griseus the Garden State’s state microbe, and the legislation is pending in the state Assembly.

    Microbiologist Max Häggblom, distinguished professor in the Department of Biochemistry and Microbiology, discusses the push for a state microbe.

    Who first proposed that New Jersey have a state microbe?

    Professor Doug Eveleigh in the Department of Biochemistry and Microbiology for many years advocated for a New Jersey State Microbe. John Warhol, a Rutgers graduate who studied microbiology, finally convinced the state Senate to introduce the bill. He wrote the book Dr. Warhol’s Periodic Table of Microbes, The Small Guide to Small Things and is involved in microbiology outreach.

    Why should New Jersey have a state microbe?

    We live in a microbial world, or the microbial world, as some people put it. Microbes are in us, they are on us, we need them, we use them and that’s why they matter. Microbes are not just germs. They do good things, like producing antibiotics, and what better microbe to name than Streptomyces griseus, which in many ways galvanized the pharmaceutical industry in New Jersey, providing thousands of jobs?

    How important was the discovery of Streptomyces griseus and streptomycin in terms of microbial and medical history?

    It changed the world. The Rutgers legacy is one of launching soil and environmental microbiology as active research disciplines. In 1903, Jacob Lipman became the nation’s first professor of soil bacteriology. Waksman, as a student, found that the filamentous actinomycetes in soil were actually bacteria and not fungi. Several years later, he shifted his research emphasis to antibiotic discoveries that eventually led back to actinomycetes, a group of poorly understood bacteria that include Streptomyces griseus, playing a central role. Waksman’s student, Boyd Woodruff, was the first student to go into antibiotic research. Woodruff developed a screening system for finding antibiotic-producing bacteria in soil. Waksman, Schatz and Bugie used that system in their discovery of streptomycin. Woodruff went to Merck and eventually headed the company’s natural products discovery division. Many different students eventually discovered about 20 antibiotics at Rutgers. Some of them were too toxic to be used in medicine – they could kill microbes and people – but some still have potential as cancer therapies. Two, neomycin and candicin, are still used today, while actinomycin is used in cancer therapy.

    Do scientists still have a lot to learn about microbes and their functions?

    Indeed. Basically, microbes are what make the earth’s biosphere function. They will do very well without us, but life would not survive without them. Microbes drive all environmental and biochemical processes.

    How much does the public know about microbes?

    Very little. The effort to name a state microbe is the beginning of trying to educate everyone about what microbes are, what they do, when they’re good, when they’re bad and their importance for humans.

    See the full article here .


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    Please help promote STEM in your local schools.

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    Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

    Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.

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  • richardmitnick 12:43 pm on July 11, 2018 Permalink | Reply
    Tags: , , Biology, , , Oxidation in Earth's history unearthed,   

    From University of Washington: “Oxygen levels on early Earth rose and fell several times before the successful Great Oxidation Event” 

    U Washington

    From University of Washington

    July 9, 2018
    Peter Kelley

    1
    The Jeerinah Formation in Western Australia, where a UW-led team found a sudden shift in nitrogen isotopes. “Nitrogen isotopes tell a story about oxygenation of the surface ocean, and this oxygenation spans hundreds of kilometers across a marine basin and lasts for somewhere less than 50 million years,” said lead author Matt Koehler.Photo Roger Buick.

    Earth’s oxygen levels rose and fell more than once hundreds of millions of years before the planetwide success of the Great Oxidation Event about 2.4 billion years ago, new research from the University of Washington shows.

    The evidence comes from a new study that indicates a second and much earlier “whiff” of oxygen in Earth’s distant past — in the atmosphere and on the surface of a large stretch of ocean — showing that the oxygenation of the Earth was a complex process of repeated trying and failing over a vast stretch of time.

    The finding also may have implications in the search for life beyond Earth. Coming years will bring powerful new ground- and space-based telescopes able to analyze the atmospheres of distant planets. This work could help keep astronomers from unduly ruling out “false negatives,” or inhabited planets that may not at first appear to be so due to undetectable oxygen levels.

    “The production and destruction of oxygen in the ocean and atmosphere over time was a war with no evidence of a clear winner, until the Great Oxidation Event,” said Matt Koehler, a UW doctoral student in Earth and space sciences and lead author of a new paper published the week of July 9 in the Proceedings of the National Academy of Sciences.

    “These transient oxygenation events were battles in the war, when the balance tipped more in favor of oxygenation.”

    In 2007, co-author Roger Buick, UW professor of Earth and space sciences, was part of an international team of scientists that found evidence of an episode — a “whiff” — of oxygen some 50 million to 100 million years before the Great Oxidation Event. This they learned by drilling deep into sedimentary rock of the Mount McRae Shale in Western Australia and analyzing the samples for the trace metals molybdenum and rhenium, accumulation of which is dependent on oxygen in the environment.

    Now, a team led by Koehler has confirmed a second such appearance of oxygen in Earth’s past, this time roughly 150 million years earlier — or about 2.66 billion years ago — and lasting for less than 50 million years. For this work they used two different proxies for oxygen — nitrogen isotopes and the element selenium — substances that, each in its way, also tell of the presence of oxygen.

    “What we have in this paper is another detection, at high resolution, of a transient whiff of oxygen,” said Koehler. “Nitrogen isotopes tell a story about oxygenation of the surface ocean, and this oxygenation spans hundreds of kilometers across a marine basin and lasts for somewhere less than 50 million years.”

    The team analyzed drill samples taken by Buick in 2012 at another site in the northwestern part of Western Australia called the Jeerinah Formation.

    The researchers drilled two cores about 300 kilometers apart but through the same sedimentary rocks — one core samples sediments deposited in shallower waters, and the other samples sediments from deeper waters. Analyzing successive layers in the rocks years shows, Buick said, a “stepwise” change in nitrogen isotopes “and then back again to zero. This can only be interpreted as meaning that there is oxygen in the environment. It’s really cool — and it’s sudden.”

    The nitrogen isotopes reveal the activity of certain marine microorganisms that use oxygen to form nitrate, and other microorganisms that use this nitrate for energy. The data collected from nitrogen isotopes sample the surface of the ocean, while selenium suggests oxygen in the air of ancient Earth. Koehler said the deep ocean was likely anoxic, or without oxygen, at the time.

    The team found plentiful selenium in the shallow hole only, meaning that it came from the nearby land, not making it to deeper water. Selenium is held in sulfur minerals on land; higher atmospheric oxygen would cause more selenium to be leached from the land through oxidative weathering — “the rusting of rocks,” Buick said — and transported to sea.

    “That selenium then accumulates in ocean sediments,” Koehler said. “So when we measure a spike in selenium abundances in ocean sediments, it could mean there was a temporary increase in atmospheric oxygen.”

    The finding, Buick and Koehler said, also has relevance for detecting life on exoplanets, or those beyond the solar system.

    “One of the strongest atmospheric biosignatures is thought to be oxygen, but this study confirms that during a planet’s transition to becoming permanently oxygenated, its surface environments may be oxic for intervals of only a few million years and then slip back into anoxia,” Buick said.

    “So, if you fail to detect oxygen in a planet’s atmosphere, that doesn’t mean that the planet is uninhabited or even that it lacks photosynthetic life. Merely that it hasn’t built up enough sources of oxygen to overwhelm the ‘sinks’ for any longer than a short interval.

    “In other words, lack of oxygen can easily be a ‘false negative’ for life.”

    Koehler added: “You could be looking at a planet and not see any oxygen — but it could be teeming with microbial life.”

    Koehler’s other co-authors are UW Earth and space sciences doctoral student Michael Kipp, former Earth and space sciences postdoctoral researcher Eva Stüeken — now a faculty member at the University of St. Andrews in Scotland — and Jonathan Zaloumis of Arizona State University.

    The research was funded by grants from NASA, the UW-based Virtual Planetary Laboratory and the National Science Foundation; drilling was funded by the Agouron Institute.

    For more information, contact Koehler at koehlerm@uw.edu or Buick at 206-543-1913 or buick@ess.washington.edu

    See the full article here .


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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 8:40 am on July 5, 2018 Permalink | Reply
    Tags: , , , Biology, , , , James Lovelock, Lynn Margulis, ,   

    From Science Alert: “These Scientists Have a Tantalising New Answer to The Mysterious ‘Gaia Puzzle’ “ 

    ScienceAlert

    From Science Alert

    5 JUL 2018
    JAMES DYKE,
    TIM LENTON

    1
    (Louis Maniquet/Unsplash)

    2
    marianaboterop

    We will likely never know how life on Earth started. Perhaps in a shallow sunlit pool.

    Or in the crushing ocean depths miles beneath the surface near fissures in the Earth’s crust that spewed out hot mineral-rich soup. While there is good evidence for life at least 3.7 billion years ago, we don’t know precisely when it started.

    But these passing aeons have produced something perhaps even more remarkable: life has persisted.

    Despite massive asteroid impacts, cataclysmic volcano activity and extreme climate change, life has managed to not just cling on to our rocky world but to thrive.

    How did this happen? Research we recently published with colleagues in Trends in Ecology and Evolution offers an important part of the answer, providing a new explanation for the Gaia hypothesis.

    Developed by scientist and inventor James Lovelock, and microbiologist Lynn Margulis, the Gaia hypothesis originally proposed that life, through its interactions with the Earth’s crust, oceans, and atmosphere, produced a stabilising effect on conditions on the surface of the planet – in particular the composition of the atmosphere and the climate.

    With such a self-regulating process in place, life has been able to survive under conditions which would have wiped it out on non-regulating planets.

    Lovelock formulated the Gaia hypothesis while working for NASA in the 1960s. He recognised that life has not been a passive passenger on Earth.

    Rather it has profoundly remodelled the planet, creating new rocks such as limestone, affecting the atmosphere by producing oxygen, and driving the cycles of elements such as nitrogen, phosphorus and carbon.

    Human-produced climate change, which is largely a consequence of us burning fossil fuels and so releasing carbon dioxide, is just the latest way life affects the Earth system.

    While it is now accepted that life is a powerful force on the planet, the Gaia hypothesis remains controversial. Despite evidence that surface temperatures have, bar a few notable exceptions, remained within the range required for widespread liquid water, many scientists attribute this simply to good luck.

    If the Earth had descended completely into an ice house or hot house (think Mars or Venus) then life would have become extinct and we would not be here to wonder about how it had persisted for so long.

    This is a form of anthropic selection argument that says there is nothing to explain.

    Clearly, life on Earth has been lucky. In the first instance, the Earth is within the habitable zone – it orbits the sun at a distance that produces surface temperatures required for liquid water.

    There are alternative and perhaps more exotic forms of life in the universe, but life as we know it requires water. Life has also been lucky to avoid very large asteroid impacts.

    A lump of rock significantly larger than the one that lead to the demise of the dinosaurs some 66 million years ago could have completely sterilised the Earth.

    But what if life had been able to push down on one side of the scales of fortune? What if life in some sense made its own luck by reducing the impacts of planetary-scale disturbances?

    This leads to the central outstanding issue in the Gaia hypothesis: how is planetary self-regulation meant to work?

    While natural selection is a powerful explanatory mechanism that can account for much of the change we observe in species over time, we have been lacking a theory that could explain how the living and non-living elements of a planet produce self-regulation.

    Consequently the Gaia hypothesis has typically been considered as interesting but speculative – and not grounded in any testable theory.

    Selecting for stability

    We think we finally have an explanation for the Gaia hypothesis. The mechanism is “sequential selection”. In principle it’s very simple.

    As life emerges on a planet it begins to affect environmental conditions, and this can organise into stabilising states which act like a thermostat and tend to persist, or destabilising runaway states such as the snowball Earth events that nearly extinguished the beginnings of complex life more than 600 million years ago.

    If it stabilises then the scene is set for further biological evolution that will in time reconfigure the set of interactions between life and planet. A famous example is the origin of oxygen-producing photosynthesis around 3 billion years ago, in a world previously devoid of oxygen.

    If these newer interactions are stabilising, then the planetary-system continues to self-regulate. But new interactions can also produce disruptions and runaway feedbacks.

    In the case of photosynthesis it led to an abrupt rise in atmospheric oxygen levels in the “Great Oxidation Event” around 2.3 billion years ago.

    This was one of the rare periods in Earth’s history where the change was so pronounced it probably wiped out much of the incumbent biosphere, effectively rebooting the system.

    The chances of life and environment spontaneously organising into self-regulating states may be much higher than you would expect.

    In fact, given sufficient biodiversity, it may be extremely likely. But there is a limit to this stability.

    Push the system too far and it may go beyond a tipping point and rapidly collapse to a new and potentially very different state.

    This isn’t a purely theoretical exercise, as we think we may able to test the theory in a number of different ways. At the smallest scale that would involve experiments with diverse bacterial colonies.

    On a much larger scale it would involve searching for other biospheres around other stars which we could use to estimate the total number of biospheres in the universe – and so not only how likely it is for life to emerge, but also to persist.

    The relevance of our findings to current concerns over climate change has not escaped us. Whatever humans do life will carry on in one way or another.

    But if we continue to emit greenhouse gasses and so change the atmosphere, then we risk producing dangerous and potentially runaway climate change.

    This could eventually stop human civilisation affecting the atmosphere, if only because there will not be any human civilisation left.

    The ConversationGaian self-regulation may be very effective. But there is no evidence that it prefers one form of life over another. Countless species have emerged and then disappeared from the Earth over the past 3.7 billion years.

    We have no reason to think that Homo sapiens are any different in that respect.

    See the full article here .


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  • richardmitnick 12:24 am on July 2, 2018 Permalink | Reply
    Tags: Biology, C6orf106 or "C6", , , , Gene discovery unlocks mysteries of our immunity, , Our immune system   

    From Commonwealth Scientific and Industrial Research Organisation CSIRO: “Gene discovery unlocks mysteries of our immunity” 

    CSIRO bloc

    From Commonwealth Scientific and Industrial Research Organisation CSIRO

    7.1.18

    Ofa Fitzgibbons
    Communication Advisor
    +61 2 4960 6188
    Ofa.Fitzgibbons@csiro.au

    Australia’s national science agency CSIRO has identified a new gene that plays a critical role in regulating the body’s immune response to infection and disease.

    1
    The C6orf106 or “C6” gene. No image credit.

    The discovery could lead to the development of new treatments for influenza, arthritis and even cancer.

    The gene, called C6orf106 or “C6”, controls the production of proteins involved in infectious diseases, cancer and diabetes. The gene has existed for 500 million years, but its potential is only now understood.

    “Our immune system produces proteins called cytokines that help fortify the immune system and work to prevent viruses and other pathogens from replicating and causing disease,” CSIRO researcher Dr Cameron Stewart said.

    “C6 regulates this process by switching off the production of certain cytokines to stop our immune response from spiralling out of control.

    “The cytokines regulated by C6 are implicated in a variety of diseases including cancer, diabetes and inflammatory disorders such as rheumatoid arthritis.”

    The discovery helps improve our understanding of our immune system, and it is hoped that this understanding will enable scientists to develop new, more targeted therapies.

    Dr Rebecca Ambrose was part of the CSIRO team that discovered the gene, and co-authored the recent paper announcing the discovery in the Journal of Biological Chemistry.

    “Even though the human genome was first fully sequenced in 2003, there are still thousands of genes that we know very little about,” Dr Rebecca Ambrose, a former CSIRO researcher, now based at the Hudson Institute of Medical Research said.

    “It’s exciting to consider that C6 has existed for more than 500 million years, preserved and passed down from simple organisms all the way to humans. But only now are we gaining insights into its importance.”

    Having discovered the function of C6, the researchers are awarded the privilege of naming it, and are enlisting the help of the community to do so.

    “The current name, C6orf106, reflects the gene’s location within the human genome, rather than relating to any particular function,” Dr Stewart said.

    “We think we can do better than that, and are inviting suggestions from the public.”

    A shortlist of names will be made available for final approval by a governing third party.

    The breakthrough builds on decades of work in infectious diseases, by researchers from CSIRO, Australia’s national science agency.

    See the full article here .


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    CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

     
  • richardmitnick 10:37 am on June 28, 2018 Permalink | Reply
    Tags: , Biology, , , Phase contrast tomography, The human cerebellum   

    From DESY: “Google Maps for the cerebellum” 

    DESY
    From DESY

    Scientists image millions of nerve cells with the help of PETRA III [Image is below].

    2018/06/28

    1
    Result of the phase contrast X-ray tomography at DESY’s X-ray source PETRA III. Credit: Töpperiwen et al., Universität Göttingen

    A team of researchers from Göttingen has successfully applied a special variant of X-ray imaging to brain tissue. With the combination of high-resolution measurements at DESY’s X-ray light source PETRA III and data from a laboratory X-ray source, Tim Salditt’s group from the Institute of X-ray Physics at the Georg August University of Göttingen was able to visualize about 1.8 million nerve cells in the cerebellar cortex. The researchers describe the investigations with the so-called phase contrast tomography in the Proceedings of the National Academy of Sciences (PNAS).

    The human cerebellum contains about 80 percent of all nerve cells in 10 percent of the brain volume – one cubic millimeter can therefore contain more than one million nerve cells. These process signals that mainly control learned and unconscious movement sequences. However, their exact positions and neighbourhood relationships are largely unknown. “Tomography in the so-called phase contrast mode and subsequent automated image processing enables the cells to be located and displayed in their exact position,” explains Mareike Töpperwien from the Institute of X-ray Physics at the University of Göttingen, lead author of the publication.

    The scientists used a biopsy needle to take cylindrical tissue samples from tissue blocks and investigated them with a special phase contrast tomograph developed by Salditt’s research group. Conventional instruments have the disadvantage that small structures and tissues of low density – as in nerve cells – provide little to no contrast and therefore cannot be imaged. The innovative method of the Göttingen researchers is not based on the absorption of X-rays, but on the altered propagation speed of X-rays. The resulting differences in propagation time become indirectly visible through beam propagation on a free flight path between object and detector.

    “For biological samples, this ‘phase’ contrast is up to 1000 times more intense and is used at PETRA III for imaging structures in the sub-micrometer range,” explains DESY researcher Michael Sprung, head of the P10 measuring station where the investigations took place. One micrometer is a thousandth of a millimeter.

    In order to obtain sharp images, the scientists process the images by computer. They can then reconstruct the three-dimensional electron density of the tissue from the entire tomographic image series. “In the future, we will also use this method to show pathological changes, such as those occurring in neurodegenerative diseases, in three dimensions, for example changes in nerve tissue in diseases such as multiple sclerosis,” explains co-author Christine Stadelmann-Nessler, neuropathologist at Göttingen University Medicine.

    The combination of images of different magnifications enabled the Göttingen team to map the cerebellum over many orders of magnitude. “In the future, we want to be able to zoom even further into interesting brain regions, almost like on Google Maps,” says Salditt.

    See the full article here .


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    desi

    DESY is one of the world’s leading accelerator centres. Researchers use the large-scale facilities at DESY to explore the microcosm in all its variety – from the interactions of tiny elementary particles and the behaviour of new types of nanomaterials to biomolecular processes that are essential to life. The accelerators and detectors that DESY develops and builds are unique research tools. The facilities generate the world’s most intense X-ray light, accelerate particles to record energies and open completely new windows onto the universe. 
That makes DESY not only a magnet for more than 3000 guest researchers from over 40 countries every year, but also a coveted partner for national and international cooperations. Committed young researchers find an exciting interdisciplinary setting at DESY. The research centre offers specialized training for a large number of professions. DESY cooperates with industry and business to promote new technologies that will benefit society and encourage innovations. This also benefits the metropolitan regions of the two DESY locations, Hamburg and Zeuthen near Berlin.

    DESY Petra III interior


    DESY Petra III

    DESY/FLASH

    H1 detector at DESY HERA ring

    DESY DORIS III

     
  • richardmitnick 3:19 pm on June 19, 2018 Permalink | Reply
    Tags: Biology, , ,   

    From World Community Grid (WCG): “Microbiome Immunity Project Researchers Create Ambitious Plans for Data” 

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    From World Community Grid (WCG)

    By: Dr. Tomasz Kościółek and Bryn Taylor
    University of California San Diego
    19 Jun 2018

    Summary
    The Microbiome Immunity Project researchers—from Boston, New York, and San Diego—met in person a few weeks ago to make plans that include a 3D map of the protein universe and other far-ranging uses for the data from the project.


    The research team members pictured above are (from left to right): Vladimir Gligorijevic (Simons Foundation’s Flatiron Institute), Tommi Vatanen (Broad Institute of MIT and Harvard), Tomasz Kosciolek (University of California San Diego), Rob Knight (University of California San Diego), Rich Bonneau (Simons Foundation’s Flatiron Institute), Doug Renfrew (Simons Foundation’s Flatiron Institute), Bryn Taylor (University of California San Diego), Julia Koehler Leman (Simons Foundation’s Flatiron Institute). Visit the project’s Research Participants page for additional team members.

    During the week of May 28, researchers from all Microbiome Immunity Project (MIP) institutions (University of California San Diego, Broad Institute of MIT and Harvard, and the Simons Foundation’s Flatiron Institute) met in San Diego to discuss updates on the project and plan future work.

    Our technical discussions included a complete overview of the practical aspects of the project, including data preparation, pre-processing, grid computations, and post-processing on our machines.

    We were excited to notice that if we keep the current momentum of producing new structures for the project, we will double the universe of known protein structures (compared to the Protein Data Bank) by mid-2019! We also planned how to extract the most useful information from our data, store it effectively for future use, and extend our exploration strategies.

    We outlined three major areas we want to focus on over the next six months.

    Structure-Aided Function Predictions

    We can use the structures of proteins to gain insight into protein function—or what the proteins actually do. Building on research from MIP co-principal investigator Richard Bonneau’s lab, we will extend their state-of-the-art algorithms to predict protein function using structural models generated through MIP. Using this new methodology based on deep learning, akin to the artificial intelligence algorithms of IBM, we hope to see improvements over more simplistic methods and provide interesting examples from the microbiome (e.g., discover new genes creating antibiotic resistance).

    Map of the Protein Universe

    Together we produce hundreds of high-quality protein models every month! To help researchers navigate this ever-growing space, we need to put them into perspective of what we already know about protein structures and create a 3D map of the “protein universe.” This map will illustrate how the MIP has eliminated the “dark matter” from this space one structure at a time. It will also be made available as a resource for other researchers to explore interactively.

    Structural and Functional Landscape of the Human Gut Microbiome

    We want to show what is currently known about the gut microbiome in terms of functional annotations and how our function prediction methods can help us bridge the gap in understanding of gene functions. Specifically, we want to follow up with examples from early childhood microbiome cohorts (relevant to Type-1 diabetes, or T1D) and discuss how our methodology can help us to better understand T1D and inflammatory bowel disease.

    The future of the Microbiome Immunity Project is really exciting, thanks to everyone who makes our research possible. Together we are making meaningful contributions to not one, but many scientific problems!

    See the full article here.


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    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”
    WCG projects run on BOINC software from UC Berkeley.
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    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

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    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

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    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

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  • richardmitnick 4:44 pm on June 16, 2018 Permalink | Reply
    Tags: , , Biology, , , New type of photosynthesis discovered   

    From Imperial College London: “New type of photosynthesis discovered” 

    Imperial College London
    From Imperial College London

    15 June 2018
    Hayley Dunning

    1
    Colony of cells where colours represent chlorophyll-a and -f driven photosynthesis. Dennis Nuernberg

    The discovery changes our understanding of the basic mechanism of photosynthesis and should rewrite the textbooks.

    It will also tailor the way we hunt for alien life and provide insights into how we could engineer more efficient crops that take advantage of longer wavelengths of light.

    The discovery, published today in Science, was led by Imperial College London, supported by the BBSRC, and involved groups from the ANU in Canberra, the CNRS in Paris and Saclay and the CNR in Milan.

    The vast majority of life on Earth uses visible red light in the process of photosynthesis, but the new type uses near-infrared light instead. It was detected in a wide range of cyanobacteria (blue-green algae) when they grow in near-infrared light, found in shaded conditions like bacterial mats in Yellowstone and in beach rock in Australia.

    As scientists have now discovered, it also occurs in a cupboard fitted with infrared LEDs in Imperial College London.

    Photosynthesis beyond the red limit

    The standard, near-universal type of photosynthesis uses the green pigment, chlorophyll-a, both to collect light and use its energy to make useful biochemicals and oxygen. The way chlorophyll-a absorbs light means only the energy from red light can be used for photosynthesis.

    Since chlorophyll-a is present in all plants, algae and cyanobacteria that we know of, it was considered that the energy of red light set the ‘red limit’ for photosynthesis; that is, the minimum amount of energy needed to do the demanding chemistry that produces oxygen. The red limit is used in astrobiology to judge whether complex life could have evolved on planets in other solar systems.

    However, when some cyanobacteria are grown under near-infrared light, the standard chlorophyll-a-containing systems shut down and different systems containing a different kind of chlorophyll, chlorophyll-f, takes over.

    2
    Cross-section of beach rock (Heron Island, Australia) showing chlorophyll-f containing cyanobacteria (green band) growing deep into the rock, several millimetres below the surface. Dennis Nuernberg

    Until now, it was thought that chlorophyll-f just harvested the light. The new research shows that instead chlorophyll-f plays the key role in photosynthesis under shaded conditions, using lower-energy infrared light to do the complex chemistry. This is photosynthesis ‘beyond the red limit’.

    Lead researcher Professor Bill Rutherford, from the Department of Life Sciences at Imperial, said: “The new form of photosynthesis made us rethink what we thought was possible. It also changes how we understand the key events at the heart of standard photosynthesis. This is textbook changing stuff.”

    Preventing damage by light

    Another cyanobacterium, Acaryochloris, is already known to do photosynthesis beyond the red limit. However, because it occurs in just this one species, with a very specific habitat, it had been considered a ‘one-off’. Acaryochloris lives underneath a green sea-squirt that shades out most of the visible light leaving just the near-infrared.

    The chlorophyll-f based photosynthesis reported today represents a third type of photosynthesis that is widespread. However, it is only used in special infrared-rich shaded conditions; in normal light conditions, the standard red form of photosynthesis is used.

    It was thought that light damage would be more severe beyond the red limit, but the new study shows that it is not a problem in stable, shaded environments.

    Co-author Dr Andrea Fantuzzi, from the Department of Life Sciences at Imperial, said: “Finding a type of photosynthesis that works beyond the red limit changes our understanding of the energy requirements of photosynthesis. This provides insights into light energy use and into mechanisms that protect the systems against damage by light.”

    These insights could be useful for researchers trying to engineer crops to perform more efficient photosynthesis by using a wider range of light. How these cyanobacteria protect themselves from damage caused by variations in the brightness of light could help researchers discover what is feasible to engineer into crop plants.

    Textbook-changing insights

    More detail could be seen in the new systems than has ever been seen before in the standard chlorophyll-a systems. The chlorophylls often termed ‘accessory’ chlorophylls were actually performing the crucial chemical step, rather than the textbook ‘special pair’ of chlorophylls in the centre of the complex.

    This indicates that this pattern holds for the other types of photosynthesis, which would change the textbook view of how the dominant form of photosynthesis works.

    Dr Dennis Nürnberg, the first author and initiator of the study, said: “I did not expect that my interest in cyanobacteria and their diverse lifestyles would snowball into a major change in how we understand photosynthesis. It is amazing what is still out there in nature waiting to be discovered.”

    Peter Burlinson, lead for frontier bioscience at BBSRC – UKRI says, “This is an important discovery in photosynthesis, a process that plays a crucial role in the biology of the crops that feed the world. Discoveries like this push the boundaries of our understanding of life and Professor Bill Rutherford and the team at Imperial should be congratulated for revealing a new perspective on such a fundamental process.”

    See the full article here .


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    Imperial College London

    Imperial College London is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialisation, harnessing science and innovation to tackle global challenges.

     
  • richardmitnick 12:21 pm on June 15, 2018 Permalink | Reply
    Tags: , Biology, Retinal,   

    From SLAC Lab: “Scientists Make the First Molecular Movie of One of Nature’s Most Widely Used Light Sensors” 


    From SLAC Lab

    June 14, 2018
    Glennda Chui


    A molecular movie based on experimental data shows the retinal molecule, in green, changing shape along with parts of its surrounding protein pocket, in pink, when hit by light. The changing numbers are distances in angstroms. One angstrom is one ten-billionth of a meter. That’s roughly the diameter of the smallest atoms. (Paul Scherrer Institute, Andy Freeberg/SLAC)

    The X-ray laser movie shows what happens when light hits retinal, a key part of vision in animals and photosynthesis in microbes. The action takes place in a trillionth of an eye blink.

    Scientists have made the first molecular movie of the instant when light hits a sensor that’s widely used in nature for probing the environment and harvesting energy from light. The sensor, a form of vitamin A known as retinal, is central to a number of important light-driven processes in people, animals, microbes and algae, including human vision and some forms of photosynthesis, and the movie shows it changing shape in a trillionth of an eye blink.

    “To my knowledge, nobody has measured changes in a retinal biosensor so quickly and so accurately,” said Jörg Standfuss, a biologist at the Paul Scherrer Institute (PSI) in Switzerland who led the research at the Department of Energy’s SLAC National Accelerator Laboratory. “And the fact that we saw just the opposite of what we intuitively expected was spectacular and surprising to us.”

    The team carried out their experiments at the lab’s Linac Coherent Light Source (LCLS) X-ray laser and reported the results today in Science.

    SLAC/LCLS

    Comming soon (A really bad attempt at lab humor. In fact, it will be a while).

    SLAC/LCLS II projected view

    In the past, scientists had to fill the gaps in their knowledge about retinal’s behavior by making inferences based on theory and computer simulations, said Mark Hunter, a staff scientist at LCLS and paper co-author. But in this study, “LCLS’s super-short pulses allowed us to collect data on where the atoms actually were in space and how that changed over time,” he said, “so it gave us a much more direct visualization of molecules in motion.”

    Colorful Lakes and Arching Cats

    Retinal is so central to human vision – it’s named for the retina at the back of the eye – that scientists have been studying it for nearly a century, steadily building a more detailed picture of how it works. It’s also used in the burgeoning field of optogenetics to turn groups of nerve cells on and off, revealing how the brain works and how things go wrong in conditions like depression, stroke and addiction.

    The retinal studied in this experiment came from salt-loving microbes that use it to harvest energy from the sun. (Fun fact: Purple and orange-red pigments in these microbes give the briny waters they live in, from San Francisco Bay salt ponds to Senegal’s Lake Retba, their incredibly vivid colors.)

    Retinal does its job while snuggled deep into a pocket of specialized proteins in the membrane of the cell. When hit by light, the retinal changes shape – in this case it curves, like a cat arching its back. This creates a signal that’s transmitted by the protein into the cell’s interior, initiating photosynthesis or vision.

    Scientists thought retinal set off the signal by pushing on the protein pocket as it changed shape. But the LCLS experiments found just the opposite: The pocket actually changed shape first, creating space for the retinal to perform its arching-cat maneuver. Nearby water molecules also moved aside and made room, Standfuss said. It all took place within 200 to 500 femtoseconds, or millionths of a billionth of a second. That’s about a trillionth of the blink of an eye, making this one of the fastest chemical reactions known in living things.

    “In retrospect, this makes a lot of sense,” Standfuss said. “We always say seeing is believing in structural biology, and in this case it’s very true. The molecular movie we made makes it so obvious what’s going on that you can immediately grasp it. This solves a very important piece of the puzzle of how retinal works that people have been wondering about.”

    The protein pocket’s initial movements are triggered by small changes in electrical charge that rearrange certain chemical bonds, he said. These movements guide the retinal’s response and make it much more efficient, which is why it requires only a few photons of light and why nature can use that light so effectively.


    In this pair of molecular movies we see the retinal molecule (in the middle of each frame) and parts of its surrounding protein pocket with their shapes defined by their electron clouds (blue lines). The top frame shows the retinal molecule from the side, and the bottom one shows it from the top as it curves in response to light. (Paul Scherrer Institute)

    Catching Molecules in Action

    How can you watch something so small that happens so fast? The X-ray laser was key, Standfuss said. LCLS produces brilliant pulses of X-ray laser light that scatter off the electrons in a sample and reveal how its atoms are arranged. Like a camera with an extreme zoom lens and ultrafast shutter speed, the X-ray laser can also make snapshots of molecules moving, breaking apart and interacting with each other.

    In this case, the researchers looked at samples of retinal snuggled into pockets of bacteriorhodopsin, a purple protein found in simple microbes like those in the salt ponds.

    After years of effort, PSI postdoctoral researcher Przemyslaw Nogly, the lead author of the report, found ways to pack these retinal-protein pairs into thousands and thousands of tiny but well-ordered crystals. One after another, crystals were hit with light from an optical laser – a stand-in for sunlight – followed by X-ray laser pulses to record the response. Then Nogly and the team boiled down data into 20 snapshots and assembled them into stop-action movies that show the retinal moving in sync with its protein pocket.

    Proteins like bacteriorhodopsin that sit in cell membranes are notoriously difficult to study because it’s so hard to form them into crystals for X-ray experiments, Hunter said. But scientists have learned that they crystallize more readily when embedded in a fatty, toothpaste-like sludge that mimics their natural environment, and that’s how these crystals were formed and delivered into the X-ray beam.

    The researchers were also able to detect “protein quakes,” vibrations that release some of the energy deposited by the light flashes. These had been predicted by theory and came off as expected.

    Standfuss said he has spent most of his career studying retinal and its role in vision, which involves slightly different shape changes in the protein-embedded molecule. “I really hope that we can now study the same reaction in many different systems,” he said. “Now that we see for the first time how it works in one particular bacterial protein, I want to understand how it works in the human eye as well.”

    LCLS researchers Sergio Carbajo, Jason Koglin, Matthew Seaberg and Thomas Lane were co-authors of this study. Other contributors came from PSI, the University of Gothenburg in Sweden, the Fritz Haber Center for Molecular Dynamics at the Hebrew University of Jerusalem, the RIKEN SPring-8 Center and Kyoto University in Japan, the Center for Free-Electron Laser Science at DESY in Germany and Arizona State University. Major funding came from the European Horizon 2020 Program, the Swedish Research Council and the Swiss National Science Foundation.

    See the full article here .


    five-ways-keep-your-child-safe-school-shootings
    Please help promote STEM in your local schools.

    Stem Education Coalition

    SLAC Campus
    SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.

     
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