CORE C - Infection and Inflammation Core

CORE C - 感染和炎症核心

基本信息

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
项目类别：
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

项目摘要

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.

概括核心C设施支持研究项目的具体目的，包括计划和执行实验性败血症队列研究，全血样本的血液学分析以及测量多种循环糖蛋白，包括对标记的比较研究败血症发作和进展过程中的炎症过程。因此，核心提供支持解决该程序的中心假设，蛋白质糖基化和糖蛋白重塑改变了脓毒症的凝血病和炎症。 Core C提供必不可少的实验和技术功能包括分析源自小鼠的实验和临床生物样品，人类包括全血，血清，血浆以及尿液。与核心在鼠标中开发了一个实验性败血症协议，包括具有特定阈值的数据包含的标准化和可再现的病原体感染和监测代表小鼠败血症的发作和进展，以响应五种不同的人类细菌病原体和临床分离株。这种方法使比较研究涵盖了这三个项目中的每个项目都在揭示了提供一定程度的不同致病途径的情况下由于特定的细菌病原体，败血症发病机理的分层。这些研究将进一步如本应用程序的研究项目所示。此外，核心设施将完成小鼠血液样本以及人类志愿者和败血症患者血液的血液学分析包括对白色和红细胞的测量，血细胞比容值，血红蛋白丰度以及多个血小板指标。在要求时进行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，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的本地项目研究人员，将是用相同的设备进行标准化，用于在项目研究的第二站点。核心功能还将从血清生成多路复用分析物数据集，在健康和败血症的背景下，血浆或小鼠和人类的尿液样品。这些多重实验使用研究者选择的和可定制的测定法，得出定量测量必不可少的细胞因子，生长因子和生理的其他各种生物学指标系统尤其是那些影响炎症过程的系统。一千多个蛋白质可以是在各种分析物中有选择性测量的无法常规检测并使用质谱法准确测量。因此，核心提供了意味着要查询较低的丰度蛋白，这些蛋白质难以量化。核心C将提高速率计划研究的进展并促进了提出的研究之间的研究整合和协同作用。