Collectins and Innate Defense against Inhaled Pathogens
Collectins and Innate Defense against Inhaled Pathogens
批准号:
7924146
负责人:
BARBARA A SEATON
金额:
$193.83万
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:
2009-09-01 至 2012-08-31
中文摘要
本项目的中心主题是了解宿主的先天防御机制
英文摘要
The central theme of the Program Project is to understand the innate host defense mechanisms against
inhaled pathogens by the two pulmonary collectins, surfactant proteins A and D (SP-A, SP-D). This
understanding is important not only in the context of prevalent respiratory infections but also those
associated with serious global biothreats ¿ the emergence of antibiotic-resistant organisms; evolution and
rapid spread of more lethal respiratory viruses; and potential use of inhaled pathogens in acts of
bioterrorism. Effective pulmonary host defense requires early recognition of microorganisms. Following
deposition of an organism into the respiratory tract, there is a critical window of opportunity for pathogen
clearance; delayed response favors infection. The pulmonary collectins play a front-line role in the innate
defense against many gram-negative and positive bacteria and their endotoxins, mycobacteria, pathogenic
fungi, and obligate intracellular pathogens including influenza A (lAV) and other potentially lethal viruses.
The innate defense properties of pulmonary collectins depend upon their rapid recognition and, in some
cases, neutralization of inhaled microorganisms based on pattern recognition of highly-conserved microbial
surface components such as N-linked high-mannose glycans on lAV and gram-negative lipolysaccharide
(endotoxin). Other studies show that animals deficient in lung collectins show significantly increased
susceptibility to microbiological challenges. Studies of recombinant truncated SP-A and SP-D in murine
models of allergy and infection have offered the possibility that aerosolized forms of these proteins delivered
by inhalation may have therapeutic potential in controlling respiratory infection, inflammation, and allergy in
humans. In this program project, a highly collaborative and focused group of projects using complementary
approaches, including x-ray crystallography, mutagenesis, spectroscopy, in vitro and in vivo analyses using
animal models, aim specifically at innate responses of collectins, and proteins such as KGF that modulate
their activity, to lAV and gram-negative bacteria both to gain mechanistic understanding and assist design of
potential collectin-based therapeutics with increased antimicrobial activities.
.
期刊论文(5)
专著(0)
科研奖励(0)
会议论文
Crystallographic complexes of surfactant protein A and carbohydrates reveal ligand-induced conformational change.
表面活性剂蛋白 A 和碳水化合物的晶体复合物揭示了配体诱导的构象变化。
DOI:
10.1074/jbc.m110.175265
发表时间:
2011
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
[Shang,Feifei, Rynkiewicz,MichaelJ, McCormack,FrancisX, Wu,Huixing, Cafarella,TanyaM, Head,JamesF, Seaton,BarbaraA]
通讯作者:
Seaton,BarbaraA
Differential Ligand Binding Specificities of the Pulmonary Collectins Are Determined by the Conformational Freedom of a Surface Loop.
肺集合素的差异配体结合特异性由表面环的构象自由度决定。
DOI:
10.1021/acs.biochem.6b01313
发表时间:
2017
期刊:
Biochemistry
影响因子:
2.9
作者:
[Rynkiewicz,MichaelJ, Wu,Huixing, Cafarella,TanyaR, Nikolaidis,NikolaosM, Head,JamesF, Seaton,BarbaraA, McCormack,FrancisX]
通讯作者:
McCormack,FrancisX
DOI:
10.1016/j.bbamem.2009.11.024
发表时间:
2010-04
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
影响因子:
3.4
作者:
[Mendelsohn, Richard, Mao, Guangru, Flach, Carol R.]
通讯作者:
Flach, Carol R.
Collectins and Innate Defense against Inhaled Pathogens
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批准号:7695978
-
项目类别:
-
资助金额:$203.58万
-
财政年份:2009
-
负责人:BARBARA A SEATON
-
依托单位:
Collectins and Innate Defense against Inhaled Pathogens
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批准号:7932334
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项目类别:
-
资助金额:$94.56万
-
财政年份:2009
-
负责人:BARBARA A SEATON
-
依托单位:
PHOSPHOLIPID HEAD GROUP RECOGNITION IN MEMBRANE BINDING PROTEIN ANNEXIN V
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批准号:6345252
-
项目类别:
-
资助金额:$0.38万
-
财政年份:2000
-
负责人:BARBARA A SEATON
-
依托单位:
PHOSPHOLIPID HEAD GROUP RECOGNITION IN MEMBRANE BINDING PROTEIN ANNEXIN V
-
批准号:6478976
-
项目类别:
-
资助金额:$5.36万
-
财政年份:2000
-
负责人:BARBARA A SEATON
-
依托单位:
PHOSPHOLIPID HEAD GROUP RECOGNITION IN MEMBRANE BINDING PROTEIN ANNEXIN V
-
批准号:6206447
-
项目类别:
-
资助金额:$0.38万
-
财政年份:1999
-
负责人:BARBARA A SEATON
-
依托单位:
CA BRIDGING MECHANISM & PHOSPHOLIPID HEAD GROUP RECOGNITION IN ANNEXIN V
-
批准号:6123287
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1998
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:2182572
-
项目类别:
-
资助金额:$22.45万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:6476516
-
项目类别:
-
资助金额:$26.17万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURE AND PHOSPHOLIPID INTERACTION
-
批准号:3468143
-
项目类别:
-
资助金额:$10.31万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:2444753
-
项目类别:
-
资助金额:$23.13万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:2904412
-
项目类别:
-
资助金额:$27.2万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURE AND PHOSPHOLIPID INTERACTION
-
批准号:3468145
-
项目类别:
-
资助金额:$11.9万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:6625079
-
项目类别:
-
资助金额:$26.94万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:6085175
-
项目类别:
-
资助金额:$11.53万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURE AND PHOSPHOLIPID INTERACTION
-
批准号:2182570
-
项目类别:
-
资助金额:$12.76万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:2734659
-
项目类别:
-
资助金额:$24.04万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURE AND PHOSPHOLIPID INTERACTION
-
批准号:3468144
-
项目类别:
-
资助金额:$11.23万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:6329723
-
项目类别:
-
资助金额:$25.42万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURES AND MEMBRANE INTERACTIONS
-
批准号:2182571
-
项目类别:
-
资助金额:$23.82万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
ANNEXIN CRYSTAL STRUCTURE AND PHOSPHOLIPID INTERACTION
-
批准号:3468146
-
项目类别:
-
资助金额:$11.82万
-
财政年份:1990
-
负责人:BARBARA A SEATON
-
依托单位:
国内基金
海外基金
Innate-likeB细胞受损介导凋亡细胞的清除障碍在系统性红斑狼疮发病中的作用及机制研究
-
批准号:81860295
-
项目类别:地区科学基金项目
-
资助金额:35.0万元
-
批准年份:2018
-
负责人:张伟
-
依托单位: