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Richard M Caprioli - One of the best experts on this subject based on the ideXlab platform.

  • Imaging Mass Spectrometry: Enabling a New Age of Discovery in Biology and Medicine Through Molecular Microscopy
    Journal of The American Society for Mass Spectrometry, 2015
    Co-Authors: Richard M Caprioli
    Abstract:

    Imaging mass spectrometry (IMS) has become a valuable tool for the production of molecular maps in samples ranging from solid inorganic materials to biologicals such as cells and tissues. The unique features of IMS are its ability to map a wide variety of different types of molecules, its superb molecular specificity, and its potential for Discovery since no target-specific reAgents are needed. IMS has made significant contributions in biology and medicine and promises to be a next generation tool in anatomic pathology. Graphical Abstract ᅟ

  • maldi imaging mass spectrometry spatial molecular analysis to enable a new Age of Discovery
    Journal of Proteomics, 2014
    Co-Authors: Megan M Gessel, Jeremy L Norris, Richard M Caprioli
    Abstract:

    Abstract Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses to provide unbiased visualization of the arrangement of biomolecules in tissue. As such, MALDI IMS has the capability to become a powerful new molecular technology for the biological and clinical sciences. In this review, we briefly describe several applications of MALDI IMS covering a range of molecular weights, from drugs to proteins. Current limitations and challenges are discussed along with recent developments to address these issues. This article is part of a Special Issue entitled: 20 years of Proteomics in memory of Vitaliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.

  • imaging mass spectrometry molecular microscopy for enabling a new Age of Discovery
    Proteomics, 2014
    Co-Authors: Richard M Caprioli
    Abstract:

    The molecular expression from genomic, proteomic, and metabolomic processes ongoing in living cells is enormously complex, continuously challenging our ability to measure and understand their integrated totality. Important biological studies and advances in the understanding of the biochemistry and biology of living cells have most often been preceded by innovations in the technology used to probe cells, tissues, and animals that then facilitate new insightful observations. A great deal has been learned over the decades about individual enzymes and pathways from isolated samples and extracts from a wide variety of bacterial and animal sources and much progress has been made toward integrating these findings into a framework that describes the underlying biology. This reductionist approach has and will continue to be important; however, there exists a multitude of biological and clinical problems that will only be solved using a systems approach. The innovative and groundbreaking advances in genomic technology and the resultant information has led to a dramatic increase in our ability to measure and predict many of the molecular events involving both genotypic and proteomic processes. Today, multiplex molecular interactions and pathway connectivity can be understood through both direct measurement and predictive models in an impressive attempt to understand this totality at this point in our current knowledge. Although these efforts have greatly advanced our understanding of biological processes, the end game remains far off, especially since spatial and temporal dimensions are yet to be fully explored and integrated into this view of the intact integrated cell. Further, cells react with their environment so that even the same basic cell type will have altered expression depending on their local cellular environment. Although the overall task is daunting, investigators continue to make impressive breakthroughs in understanding this complexity and interdependence. Understanding the spatial arrangement of biomolecules in tissues and cells remains an area of intense interest. Imaging platforms, such a microscopy, NMR, positron emission tomography, and many more, have brought valuable insight into this important field. One significant new molecular technology in this regard is imaging mass spectrometry (IMS), bringing unparalleled molecular specificity and sensitivity to create molecular imAge maps of molecules in tissues. In essence, one can produce a series of imAges, each presented at a discrete molecular weight (measured as m/z values), in multiple molecular dimensions of an entire sample ranging from a simple biopsy to a whole animal tissue section. Using a microprobe approach, ablation of spots on the target tissue encompassing an array across the field of interest provides the basic dataset. Each signal in the mass spectrum of each spot can be plotted over the entire array, giving rise to a molecular map of each of the signals. The spatial resolution of the map or imAge is defined by the diameter of the ablation spot and the pitch of the spots. Literally, hundreds to thousands of discrete molecular imAges can be generated from a single-array acquisition. Many different ionization modes have been used for IMS and include secondary ion MS [1], laser desorption ionization [2], MALDI [3], and desorption ESI of a number of varieties and variations [4]. All have unique capabilities and limitations and have led to an astonishing rise in the number of papers published in this field, as shown in Fig. 1. Together, these technologies have included the mapping of trace elements, low molecular weight organic molecules such as endogenous metabolites and drugs, lipids, peptides, proteins, polynucleotides, and synthetic polymers, as well as other molecules. Figure 1 Publications reporting the development and application of IMS. Data were collected from a PubMed search of the following key words: imaging mass spectrometry or mass spectrometry imaging, and “1980” (Date—Publication): “2014” ... In the biological and medical arena, the most generally useful technology for imaging biomolecules is MALDI IMS. The first description of this imaging platform and its use for imaging cells and tissues was published in 1997 where it was demonstrated that signals for peptides and proteins could be obtained directly from tissues and blots of tissues [5,6]. MALDI IMS enjoys the widest applicability to biological and medical research due to the balance among critical parameters in imAge analysis, including spatial resolution, molecular types amenable to analysis, molecular mass range, and sensitivity. For example, the MALDI MS imAge shown in Fig. 2 was obtained at 10 μm spatial resolution from a section of human kidney. Specific molecular imAges are overlaid in different colors representing unique m/z values for glomeruli (m/z = 13 787, red), tubules (m/z = 2592, green and 1618, blue) and a blood vessel (m/z = 8415, yellow). Figure 2 Molecular imAges (right panel) of specific peptides and proteins acquired by MALDI IMS at 10 μm spatial resolution from a section of human kidney and the corresponding microscopy imAge (left panel) corresponding periodic acid Schiff stain of the ... Perhaps one of the greatest opportunities and challenges for IMS lies in its clinical potential to aid diagnosis, prognosis, and effectiveness of therapy through the molecular assessment of biopsies obtained from patients [7]. Through the unique combination of the cell type specific sampling and the multiplex capabilities of the mass spectrometer, molecular signatures of specific diseased cells can be assayed where 10–20 or more proteins or metabolites can be measured virtually at the same time and at high sensitivity. For the first time, anatomical pathologists will have the tools to probe tissues directly without the limitations and expense of needing specific molecular probes. For clinical research, the potential for Discovery is maximized since target-specific reAgents such as antibodies are not required. It is clear that direct molecular mapping in disease will become increasingly important for molecular pathology in the coming years and represents a paradigm shift in this field. Although the vision of creating a functional molecular microscope goes back many years, the technology advancements recently realized in modern MS in terms of speed, sensitivity, and ablation spot size allow such a vision to become a reality. To be certain, this magnificent journey has been made possible by the many pioneering scientists whose innovative spirits in both fundamental MS and the application of imaging technology to biological studies must be recognized and applauded. Moreover, in working with colleagues in virtually every area of molecular sciences, new discoveries will be made as a consequence of our ability to look deeper into the molecular complexity of living cells while leaving the basic biological structures intact. When taken together with other molecular analytical tools available today, it is certain that IMS will be an indispensable technology in providing specific molecular information for Discovery of new and exciting biological processes and their relevancy in disease. IMS is now a newly matured technology, and it is certain that the capabilities we enjoy today will seem modest in the coming years as the technology continues to develop and research investigators push the need for higher and higher performance.

Andrew Whiten - One of the best experts on this subject based on the ideXlab platform.

Rima Arnaout - One of the best experts on this subject based on the ideXlab platform.

  • little fish big data zebrafish as a model for cardiovascular and metabolic disease
    Physical Review, 2017
    Co-Authors: Philipp Gut, Sven Reischauer, Didier Y R Stainier, Rima Arnaout
    Abstract:

    The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for Discovery and therapeutics. Animal models of human disease are cornerstones of drug Discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an Age of Discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantAges and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date.

Philipp Gut - One of the best experts on this subject based on the ideXlab platform.

  • little fish big data zebrafish as a model for cardiovascular and metabolic disease
    Physical Review, 2017
    Co-Authors: Philipp Gut, Sven Reischauer, Didier Y R Stainier, Rima Arnaout
    Abstract:

    The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for Discovery and therapeutics. Animal models of human disease are cornerstones of drug Discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis. The zebrafish model has been used for decades to study development and pathophysiology. More than ever, the specific strengths of the zebrafish model make it a prime partner in an Age of Discovery transformed by big-data approaches to genomics and disease. Zebrafish share a largely conserved physiology and anatomy with mammals. They allow a wide range of genetic manipulations, including the latest genome engineering approaches. They can be bred and studied with remarkable speed, enabling a range of large-scale phenotypic screens. Finally, zebrafish demonstrate an impressive regenerative capacity scientists hope to unlock in humans. Here, we provide a comprehensive guide on applications of zebrafish to investigate cardiovascular and metabolic diseases. We delineate advantAges and limitations of zebrafish models of human disease and summarize their most significant contributions to understanding disease progression to date.

Koen Vandelannoote - One of the best experts on this subject based on the ideXlab platform.

  • mycobacterium ulcerans population genomics to inform on the spread of buruli ulcer across central africa
    mSphere, 2019
    Co-Authors: Koen Vandelannoote, Conor J Meehan, Miriam Eddyani, Delphin Mavinga Phanzu, Kapay Kibadi, Francoise Portaels, Kurt Jordaens, Herwig Leirs, Timothy P. Stinear
    Abstract:

    ABSTRACT Buruli ulcer is a neglected tropical disease of skin and subcutaneous tissue caused by infection with the pathogen Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical villAge scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all Buruli ulcer foci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineAge of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the Buruli ulcer epidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium. IMPORTANCE Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans. The disease is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Currently, the major hurdles facing disease control are incomplete understandings of both the mode of transmission and environmental reservoirs of M. ulcerans. As decades of spasmodic environmental sampling surveys have not brought us much closer to overcoming these hurdles, the Buruli ulcer research community has recently switched to using comparative genomics. The significance of our research is in how we used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our approach shows that it might be possible to use bacterial population genomics to assess the impact of health interventions, providing valuable feedback for manAgers of disease control programs in areas where health surveillance infrastructure is poor.

  • Mycobacterium ulcerans Population Genomics To Inform on the Spread of Buruli Ulcer across Central Africa
    American Society for Microbiology, 2019
    Co-Authors: Koen Vandelannoote, Conor J Meehan, Miriam Eddyani, Delphin Mavinga Phanzu, Kapay Kibadi, Timothy P. Stinear, Francoise Portaels, Kurt Jordaens, Herwig Leirs, Simon R. Harris
    Abstract:

    Buruli ulcer is a destructive skin and soft tissue infection caused by Mycobacterium ulcerans. The disease is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Currently, the major hurdles facing disease control are incomplete understandings of both the mode of transmission and environmental reservoirs of M. ulcerans. As decades of spasmodic environmental sampling surveys have not brought us much closer to overcoming these hurdles, the Buruli ulcer research community has recently switched to using comparative genomics. The significance of our research is in how we used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our approach shows that it might be possible to use bacterial population genomics to assess the impact of health interventions, providing valuable feedback for manAgers of disease control programs in areas where health surveillance infrastructure is poor.Buruli ulcer is a neglected tropical disease of skin and subcutaneous tissue caused by infection with the pathogen Mycobacterium ulcerans. Many critical issues for disease control, such as understanding the mode of transmission and identifying source reservoirs of M. ulcerans, are still largely unknown. Here, we used genomics to reconstruct in detail the evolutionary trajectory and dynamics of M. ulcerans populations at a central African scale and at smaller geographical villAge scales. Whole-genome sequencing (WGS) data were analyzed from 179 M. ulcerans strains isolated from all Buruli ulcer foci in the Democratic Republic of the Congo, The Republic of Congo, and Angola that have ever yielded positive M. ulcerans cultures. We used both temporal associations and the study of the mycobacterial demographic history to estimate the contribution of humans as a reservoir in Buruli ulcer transmission. Our phylogeographic analysis revealed one almost exclusively predominant sublineAge of M. ulcerans that arose in Central Africa and proliferated in its different regions of endemicity during the Age of Discovery. We observed how the best sampled endemic hot spot, the Songololo territory, became an area of endemicity while the region was being colonized by Belgium (1880s). We furthermore identified temporal parallels between the observed past population fluxes of M. ulcerans from the Songololo territory and the timing of health policy changes toward control of the Buruli ulcer epidemic in that region. These findings suggest that an intervention based on detecting and treating human cases in an area of endemicity might be sufficient to break disease transmission chains, irrespective of other reservoirs of the bacterium