Dataset Information

Microdialysis Workflow for Metabotyping Superficial Pathologies: Application to Burn Injury.

ABSTRACT: Burn injury can be a devastating traumatic injury, with long-term personal and social implications for the patient. The many complex local and disseminating pathological processes underlying burn injury's clinical challenges are orchestrated from the site of injury and develop over time, yet few studies of the molecular basis of these mechanisms specifically explore the local signaling environment. Those that do are typically destructive in nature and preclude the collection of longitudinal temporal data. Burn injury therefore exemplifies a superficial temporally dynamic pathology for which experimental sampling typically prioritizes either specificity to the local burn site or continuous collection from circulation. Here, we present an exploratory approach to the targeted elucidation of complex, local, acutely temporally dynamic interstitia through its application to burn injury. Subcutaneous microdialysis is coupled with ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) analysis, permitting the application of high-throughput metabolomic profiling to samples collected both continuously and specifically from the burn site. We demonstrate this workflow's high yield of burn-altered metabolites including the complete structural elucidation of niacinamide and uric acid, two compounds potentially involved in the pathology of burn injury. Further understanding the metabolic changes induced by burn injury will help to guide therapeutic intervention in the future. This approach is equally applicable to the analysis of other tissues and pathological conditions, so it may further improve our understanding of the metabolic changes underlying a wide variety of pathological processes.

SUBMITTER: Friston D

PROVIDER: S-EPMC6533596 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Microdialysis Workflow for Metabotyping Superficial Pathologies: Application to Burn Injury.

Friston Dominic D Laycock Helen H Nagy Istvan I Want Elizabeth J EJ

Analytical chemistry 20190511 10

Burn injury can be a devastating traumatic injury, with long-term personal and social implications for the patient. The many complex local and disseminating pathological processes underlying burn injury's clinical challenges are orchestrated from the site of injury and develop over time, yet few studies of the molecular basis of these mechanisms specifically explore the local signaling environment. Those that do are typically destructive in nature and preclude the collection of longitudinal temp ...[more]

PMID: 31021084

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Project description:BACKGROUND:The last years have seen a renaissance of the vaccine area, driven by clinical needs in infectious diseases but also chronic diseases such as cancer and autoimmune disorders. Equally important are technological improvements involving nano-scale delivery platforms as well as third generation adjuvants. In parallel immunoinformatics routines have reached essential maturity for supporting central aspects in vaccinology going beyond prediction of antigenic determinants. On this basis computational vaccinology has emerged as a discipline aimed at ab-initio rational vaccine design.Here we present a computational workflow for implementing computational vaccinology covering aspects from vaccine target identification to functional characterization and epitope selection supported by a Systems Biology assessment of central aspects in host-pathogen interaction. We exemplify the procedures for Epstein Barr Virus (EBV), a clinically relevant pathogen causing chronic infection and suspected of triggering malignancies and autoimmune disorders. RESULTS:We introduce pBone/pView as a computational workflow supporting design and execution of immunoinformatics workflow modules, additionally involving aspects of results visualization, knowledge sharing and re-use. Specific elements of the workflow involve identification of vaccine targets in the realm of a Systems Biology assessment of host-pathogen interaction for identifying functionally relevant targets, as well as various methodologies for delineating B- and T-cell epitopes with particular emphasis on broad coverage of viral isolates as well as MHC alleles.Applying the workflow on EBV specifically proposes sequences from the viral proteins LMP2, EBNA2 and BALF4 as vaccine targets holding specific B- and T-cell epitopes promising broad strain and allele coverage. CONCLUSION:Based on advancements in the experimental assessment of genomes, transcriptomes and proteomes for both, pathogen and (human) host, the fundaments for rational design of vaccines have been laid out. In parallel, immunoinformatics modules have been designed and successfully applied for supporting specific aspects in vaccine design. Joining these advancements, further complemented by novel vaccine formulation and delivery aspects, have paved the way for implementing computational vaccinology for rational vaccine design tackling presently unmet vaccine challenges.

Dataset Information

Microdialysis Workflow for Metabotyping Superficial Pathologies: Application to Burn Injury.

Publications

Microdialysis Workflow for Metabotyping Superficial Pathologies: Application to Burn Injury.

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