Molecular Genetics of Coagulation Disorders
Molecular Genetics of Coagulation Disorders
批准号:
7657103
负责人:
Daniel A Lawrence
金额:
$20.12万
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-04-01 至 2014-03-31
关键词:
A MouseAnticoagulantsAntigensAtherosclerosisBiological AssayBlood Coagulation DisordersCellsChemicalsCoagulation ProcessEnsureFibrin fragment DGenomicsGoalsIndividualInflammatoryInflammatory ResponseLaboratoriesLaboratory miceLipidsLiverMeasuresMetabolicMolecular GeneticsMouse ProteinMusPlasmaResearch PersonnelScreening procedureStreptococcal InfectionsStreptococcus pyogenesStreptokinaseStressTFPITechnologyThrombosisVirulence Factorsadipokinesantithrombin III-protease complexbasecytokineinhibitor/antagonistprogramsprothrombin fragment 1responsesmall moleculesuccess
中文摘要
核心A:小鼠凝血实验室
小鼠凝血实验室核心A的目标是为项目中的每一个项目提供服务。它将提供
一系列评估凝血和抗凝活性的检测,以及血脂谱。这个
CORE还将提供炎性细胞因子和脂肪因子的分析,使用与
Luminex科技公司。核心A还将使用已建立的与血栓形成相关的小鼠蛋白质试剂盒,
和动脉粥样硬化。可用于每个项目的具体分析如下所示。堆芯
A还将协调化学中心对小分子的高通量筛选
基因组学。
项目1:核心A将对小鼠血浆进行标准凝血分析,分析将包括FV活性
以及抗原、APC活性、TFPI活性、D-二聚体、凝血酶-抗凝血酶复合体和凝血酶原片段
12次化验。还将进行ADAMTS13活性测定。
项目2:核心A将评估FVIII的表达对肝脏内质网应激的影响。化验将包括
FVIII活性和抗原,以及炎症反应和脂肪因子/细胞因子谱的分析,以及
代谢参数,如血脂分布。项目2将使用核心A的CCG组件来筛选
使用考夫曼实验室开发的独特的基于细胞的分析方法开发CHOP的小分子抑制剂。
项目3:核心A将通过测量研究中的血浆细胞因子水平来协助项目3的研究人员
用Luminex多重模式检测小鼠对A组链球菌感染的反应
技术。项目3还将使用Core A的CCG组件来筛选小分子抑制剂
A组链球菌毒力因子链激酶等。
核心A的总体目标是通过提供严格的、
标准化的化验,并确保合并后的计划比每个单独的部分更强大。
英文摘要
Core A: Mouse Coagulation Laboratory
The Mouse Coagulation Laboratory Core A has the goal to serve every project in the Program. It will provide
an array of assays assessing coagulation, and anticoagulant activities, as well as plasma lipid profiles. The
Core will also provide assays of inflammatory cytokines and of adipokines, using a mutiplex format with the
Luminex Technology. Core A will also use established kits for mouse proteins associated with thrombosis,
and atherosclerosis. The specific assays that are available for each of the projects are indicated below. Core
A will also coordinate the high through-put screening of small molecules by the Center for Chemical
Genomics.
Project 1: Core A will perform standard clotting analysis of murine plasma, assays will include FV activity
and antigen, APC activity, TFPI activity, D-Dimer, thrombin-antithrombin complex and prothrombin fragment
1+2 assays. Assays of Adamts13 activity will also be performed.
Project 2: Core A will evaluate the effect of FVIII expression on ER stress in the liver. Assays will include
FVIII activity and antigen, and analysis of inflammatory responses as well as adipokine/cytokine profiles, and
metabolic parameters such as lipid profiles. Project 2 will use the CCG component of Core A to screen for
small molecule inhibitors of CHOP using unique cell-based assays developed by the Kaufman Laboratory.
Project 3: Core A will assist the investigators of Project 3 by measuring plasma cytokine levels in studies of
the murine response to Group A Streptococcal infection using a mutiplex format with the Luminex
Technology. Project 3 will also use the CCG component of Core A to screen for small molecule inhibitors of
Group A Streptococcus virulence factors such as streptokinase.
The overall goals of Core A are to enhance the success of each individual project by providing rigorous,
standardized assays and to ensure that the combined Program is stronger than each of its individual parts.
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