个体化医疗的现状与未来-蛋白质组学.ppt

1、个体化医疗的现状与未来三. 蛋白质组学研究,吕林莉 M.D., Ph.D. 东南大学医学院,Outline,Why we study proteome? What is proteome? How to study proteome? Proteomics and disease,Why we study proteome?,Why we study proteome?为何要研究蛋白质组？,Gene expression not correlates with protein All proteins have life and death cycle Structure and chemis

2、try property of protein is more complex,(1) Gene expression not correlates with protein,The abundance of cellular protein is affected by: (a) DNA transcription rate (转录效率）(codon bias)（密码子偏倚） (b) mRNA translation rate（翻译效率） (c) Protein degradation rate（降解效率）,Apparent poor relationship betweengene exp

3、ression and protein content,(2) The life and death of a protein-dynamic change,(3) Structure and chemistry property of protein is more complex,细胞内基因水平并不直接反映蛋白质水平 蛋白质是机体功能的真正执行者 蛋白质的数目、结构和理化性质都更为复杂。,Why study the proteome when we already know genome?,“without doubt the most important of all substance

4、s of the organic kingdom, and without it life on our planet would probably not exist”. Gerardus Mulder,What is proteome?,What is Proteome?,Proteome - All the proteins expressed by a cell , tissue or organism at a particular time and under specific conditions.,Proteomics is the systematic study of al

5、l of the proteins in a cell, tissue, or organism. The analysis includes the identification, expression, localizations, functions (physiological and pathophysiological functions), and interactions of proteomes.,What is Proteomics?,“Omics” revolution: fundamental shift in strategy from - piece-by-piec

6、e to global analysis - hypothesis-driven to discovery-based research,传统分析方法 蛋白质组学分析方法,Is proteomics just what we used to call protein chemistry?,Genomics and proteomics have challenged biologists to think BIG,/research/hpp/,Branches of Proteomics,Expressional Proteomics Functional

7、Proteomics Structure Proteomics,Branches of Proteomics,Structural Proteomics,High Throughput（高通量） protein structure determination via X-ray crystallography（晶体学） NMR（核磁共振） spectroscopy（光谱） comparative molecular modeling,How to study proteome?,The Major Techniques in Current Proteomics,Two-dimensional

8、 electrophoresis IEF strip separation SDS-PAGE gel separation Mass Spectrometry Protein sequencing Peptide mapping Others Yeast two hybrid assay Protein microarray,2D Gel-Electrophoresis,Protein separation Molecular weight (MW) Isoelectric point (pI) Staining Birds-eye view of protein abundance,质谱分析

9、,第一台质谱仪是英国科学家弗朗西斯阿斯顿于1919年制成的。 阿斯顿用这台装置发现了多种元素同位素，研究了53个非放射性元素，发现了天然存在的287种核素中的212种，第一次证明原子质量亏损。 他为此荣获1922年诺贝尔化学奖。,Mass Spectrometer(质谱分析仪）三个基本组成部分,MALDI Electro-SprayIonization (ESI),Time-Of-Flight (TOF) Quadrapole Ion-Trap,ElectronMultiplier(EM),Peptide Mass Fingerprint,Cut out 2D-GelSpot,Peptide

10、Mass Fingerprint,Trypsin Digest,Peptide Mass Fingerprint,Microarray Technology,Proteomics and disease,Collapse of the single target paradigm-the need for systems biology,Old paradigm,New paradigm,Diseases are due to single genes - by knocking out the gene, or designing specific inhibitors to its pro

11、tein, disease can be cured,We have to understand gene and protein networks - proteins dont act alone effective systems have built in redundancy,While genomics can assess a patients risk for certain diseases, proteomics can tell you much more about whats actually going on in the patients body.,蛋白质组学技

12、术的应用,生物信息 学分析,抗体 微阵列,质谱分析 二维凝胶电泳,亲和纯化,蛋白质的鉴别,蛋白质丰度 分析,蛋白质相互作用 及信号网络分析,生物标志物分析 及临床应用,Drake et al. J Lipid Res. 2007 Jan;48(1):1-8.,“Proteomics is the heart of personalized medicinemore so than genetics, When youre born, youre healthy. And when youre 80, youre dying, but youve got more or less the sam

13、e genome as when you were healthy.”,Larry Gold, CEO and chairman of SomaLogic, Inc. in Boulder, CO.,Disease proteomics,Applying proteomics to foster a better understanding of disease processes Develop new biomarkers for diagnosis and early detection of disease Accelerate drug development.,Proteomic identification of subgroups of RA patientslikely to develop more sev