CORE C - Infection and Inflammation Core

CORE C - 感染和炎症核心

• 批准号: 10641842
• 负责人: JAMEY MARTH
• 金额: $ 31.18万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641842
• 关键词: Address; B-Lymphocytes; Basophils; Biological; Biological Assay; Blood; Blood Cells; Blood Coagulation Disorders; Blood Platelets; Blood Proteins; Blood specimen; Board Certification; Breeding; Calibration; Cell Lineage; Cells; Clinical; Cohort Studies; Collaborations; Colony-forming units; Comparative Study; Containment; Core Facility; Data; Data Set; Dedications; Disease; Documentation; Equipment; Erythrocytes; Glycoproteins; Growth Factor; Health; Hematocrit procedure; Hematologist; Hematology; Hemoglobin; Hour; Human; Human Resources; Human Volunteers; Immune; Infection; Inflammation; Inflammatory; Intravenous; Intubation; Laboratories; Laboratory mice; Leukocytes; Location; Maintenance; Mass Spectrum Analysis; Measurement; Measures; Monitor; Mouse Strains; Mus; Oral; Pathogenesis; Pathogenicity; Pathway interactions; Physiological; Plasma; Process; Protein Glycosylation; Proteins; Protocols documentation; Publications; Publishing; Quarantine; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; Route; Sampling; Sepsis; Serum; Site; Standardization; Stomach; Stratification; System; Techniques; Technology; Tissues; Training; Travel; Urine; Whole Blood; cohort; cytokine; design; eosinophil; experimental analysis; experimental study; genetic strain; inflammatory marker; instrumentation; intraperitoneal; monocyte; neutrophil; pathogen; pathogenic bacteria; programs; response; sample collection; septic; septic patients; synergism; training project

SUMMARY The Core C facility supports research addressing the specific aims of the projects to include the planning and execution of experimental sepsis cohort studies, hematological analyses of whole blood samples, and measurements of multiple circulating glycoproteins that includes comparative studies of markers of inflammatory processes during the onset and progression of sepsis. The Core thereby provides support addressing the central hypothesis of the program, Protein glycosylation and glycoprotein remodeling alter the coagulopathy and inflammation of sepsis. Core C provides essential experimental and technological capabilities that include the analysis of experimental and clinical biological samples derived from mouse and human species including whole blood, serum, plasma, and, when requested, urine. In collaboration with the projects, and as published, the core has developed an experimental sepsis protocol in the mouse that includes standardized and reproducible pathogen infection and monitoring with specific thresholds for data inclusion representing the onset and progression of mouse sepsis in response to five different human bacterial pathogens and clinical isolates. This approach has enabled comparative studies spanning the specific aims of each of the three projects while revealing the presence of different pathogenic pathways that provide a degree of stratification in the pathogenesis of sepsis due to specific bacterial pathogens. These studies will be further expanded as indicated in the research projects of this application. In addition, the core facility will complete hematology analyses of mouse blood samples as well as blood from human volunteers and sepsis patients to include measurements of white and red blood cells, hematocrit values, hemoglobin abundance, and multiple platelet metrics. Additional analyses when requested will include flow cytometric studies of cell abundance representing various blood cell lineages including T and B lymphocytes, neutrophils, monocytes, eosinophils, and basophils. These hematology analyses will be provided to onsite local project researchers and will be standardized with identical equipment that is used to undertake comparable hematology analyses at the second site of project research. The core facility will also generate multiplex analyte datasets from serum, plasma, or urine samples from mouse and human species in the context of health and sepsis. These multiplex experiments use investigator-selected and customizable assays yielding quantitative measurements of essential and important cytokines, growth factors, and various other biological indicators of physiological systems especially those that impinge upon inflammatory processes. Over a thousand proteins can be selectively measured in various sets of analytes, and many of these proteins are found at low abundance and cannot be routinely detected and accurately measured using mass spectrometry. The core thereby provides a means to query lower abundance proteins that are difficult to quantify otherwise. Core C will enhance the rate of progress of program research and facilitate research integration and synergies among the studies proposed.

总结 核心C设施支持研究解决项目的具体目标，包括规划和 进行实验性脓毒症队列研究，全血样本的血液学分析，以及 测量多种循环糖蛋白，包括比较研究的标志物 在脓毒症的发作和进展过程中的炎症过程。核心因此提供支持 解决了该计划的中心假设，蛋白质糖基化和糖蛋白重塑改变了蛋白质的结构。 凝血病和败血症炎症。核心C提供了必要的实验和技术 能力，包括分析来自小鼠的实验和临床生物样品， 人类物种，包括全血、血清、血浆和尿液（如需要）。联同 项目，并公布，核心已经制定了一个实验性败血症协议的小鼠，其中包括 标准化和可重复的病原体感染和监测，具有特定的数据纳入阈值 代表小鼠脓毒症响应于五种不同的人类细菌感染的发作和进展， 病原体和临床分离株。这种方法使比较研究能够跨越具体目标， 这三个项目中的每一个都揭示了不同致病途径的存在， 由于特定的细菌病原体引起的脓毒症发病机制的分层。这些研究将进一步 如本申请的研究项目中所指示的那样扩展。此外，核心设施将完成 小鼠血液样品以及来自人类志愿者和败血症患者的血液的血液学分析， 包括对白色和红细胞、血细胞比容值、血红蛋白丰度以及多种 血小板指标。如有要求，其他分析将包括细胞丰度的流式细胞术研究 代表各种血细胞谱系，包括T和B淋巴细胞，嗜中性粒细胞，单核细胞，嗜酸性粒细胞， 和嗜碱性粒细胞。这些血液学分析将提供给现场当地项目研究人员， 使用相同的设备进行标准化，用于在 二是项目研究现场。核心设施还将从血清中生成多路分析物数据集， 在健康和脓毒症的情况下，来自小鼠和人类物种的血浆或尿液样品。这些多重 实验使用的是选择性的和可定制的分析， 必需的和重要的细胞因子、生长因子和各种其他生理学的生物学指标。 系统，特别是那些影响炎症过程的系统。超过一千种蛋白质 在各种分析物中选择性地测量，并且这些蛋白质中的许多以低丰度发现， 不能使用质谱法常规检测和精确测量。因此，芯提供了 是指查询较低丰度的蛋白质，否则难以定量。核心C将提高速率 项目研究的进展情况，促进研究整合和研究之间的协同作用。