Mapping the blood cell protein complexosome
绘制血细胞蛋白复合体图谱
基本信息
- 批准号:9160716
- 负责人:
- 金额:$ 25.05万
- 依托单位:
- 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:2016-07-01 至 2019-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAnemiaAplastic AnemiaBinding ProteinsBiochemicalBiological AssayBiologyBloodBlood CellsCell LineCell NucleusCell ShapeCell physiologyCellsComplexComputer SimulationCytoplasmic ProteinData SetDefectDevelopmentDiseaseErythroblastsErythrocytesExcisionFoundationsFractionationFutureGrantHematological DiseaseHematopoieticHemoglobinHumanImmunoprecipitationInformation NetworksKidney FailureLabelLeadLongevityMacromolecular ComplexesMammalsMapsMass Spectrum AnalysisMeasuresMegaloblastic AnemiaMembraneMembrane ProteinsMetabolicMethodsModelingMolecularMultipotent Stem CellsMultiprotein ComplexesMusOrganellesOryctolagus cuniculusPathway interactionsPilot ProjectsPlayProductionPropertyProtein BiochemistryProteinsProteomicsRecombinantsRecoveryRoleShapesShotgunsSystemTechniquesTestingTransfectionWorkbasecell typecomparativegene functionimmortalized cellinsightmacromoleculenetwork modelsnew technologynoveloxygen transportprogenitorprotein complexprotein expressionprotein protein interactionresearch studyresponsetranscriptome sequencingwasting
项目摘要
ABSTRACT
Erythrocytes (red blood cells; RBCs) and their progenitors express distinct proteins, which underlie their unique
biology, and which provide a molecular basis for many blood diseases, including diverse anemias, such as
those arising during renal failures as a result of low red blood cell production and lifespan. Importantly,
mammalian RBCs lack nuclei and other major organelles, and hence neither transcriptional profiling by RNA-
sequencing nor recombinant transfection—powerful techniques in other cell types—can be used to reveal RBC
gene functions and pathways. Proteomics methods, in contrast, allow for a detailed analysis of RBC proteins,
and pioneering studies have revealed that RBCs, while dominated by hemoglobin (98%), express on the order
of 1,500 to 2,000 distinct proteins. Many of these proteins play critical roles in erythrocyte function, including
key metabolic and bioenergy roles, and cytoskeletal roles in controlling RBC cell shape. More than 500
proteins in RBCs are of entirely unknown function. A fundamental question in RBC biology is thus how all of
these proteins work together to support proper RBC function and development. Building deep mechanistic
understanding of RBC biology requires accurately delineating the precise membership of protein complexes
specific to RBCs, as these carry out key functions unique to these cells. We propose to perform the first
systematic, global exploration of native protein-protein interactions (PPIs) in RBCs, using a powerful new
technology to examine those interactions directly among endogenous proteins in human and other mammalian
RBCs. Our proposed experiments combine protein biochemistry, quantitative mass spectrometry proteomics
and integrative computer modeling to reliably define the extended PPI networks and multiprotein complexes
native to RBCs, helping to lay rich new mechanistic foundations for interpreting RBC biology. By the end of this
grant, we will have performed nearly 2,000 mass spectrometry experiments on native protein complexes
isolated from primary RBCs and their progenitors, defining the RBC interactome, including both shared and
novel protein complexes, to an unprecedented degree. As a result of this work, RBCs will be the first primary
human cell type with a near complete map of stable protein complexes, giving new insights into erythrocyte
biology and development, and laying the foundation for future attempts to intervene, chemically or genetically,
in diseases affecting these critical cells.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Andrew EMILI其他文献
Andrew EMILI的其他文献
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{{ truncateString('Andrew EMILI', 18)}}的其他基金
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