美国洛克菲勒大学质谱学与气体离子化学实验室：Brian T. Chait教授
The Laboratory of mass spectrometry and gaseous ion chemistry uses mass spectrometry as a tool for investigating 1) properties and reactions of gaseous ions, 2) the phenomena involved in ionization processes such as laser desorption ionization and electrospray ionization, and 3) a variety of biological and biochemical phenomena. For the past 29 years, they have also served as a Biotechnology Research Resource of the U.S. National Institutes of Health, and as such they have three major areas of activity: basic research in mass spectrometry and ion chemistry, collaborative research involving mass spectrometry and various biomedical disciplines, and service work for a widespread biomedical user community.
Their basic research for the last several years has been concerned primarily with matrix-assisted laser desorption mass spectrometry and electrospray ionization mass spectrometry. These two techniques provide means for the volatilization and ionization of involatile and fragile organic molecules and permit the use of mass spectrometry for the investigation of hitherto inaccessible compounds such as proteins and oligonucleotides. They have designed and constructed a variety of matrix-laser desorption ionization mass spectrometers, and they have shown that the instruments can be used to measure the molecular masses of peptides and proteins with high accuracies and sensitivities. They have also developed techniques for investigating crude and partially purified biological extracts by laser desorption mass spectrometry and have used the technique to assist in the solution of a large number of biological problems. They continue to investigate the physical and chemical processes that govern
the desorption and ionization of large molecules by laser irradiation and are investigating various approaches for sequencing proteins and obtaining detailed information about modifications such as phosphorylation. They have also designed and constructed electrospray ionization mass spectrometers and are investigating the physicochemical phenomena whereby highly charged liquid droplets directly produce biomolecular ions.
Increasingly, they are exploring the utility of mass spectrometry for rapidly identifying and quantifying proteins, elucidating posttranslational modifications, mapping compact protein domains and probing protein-protein and protein-DNA interactions. Major current goals of the laboratory are to:
Develop improved instrumentation for rapid, sensitive fragmentation analysis of peptides for protein identification.
Develop improved instrumentation for ultra-high sensitivity detection of phosphopeptides.
Study the origin of the “chemical noise” background and develop means for reducing it or its effects. An ultimate goal is to detect single molecules of interest.
Develop improved methodologies for studying protein interactions. Ultimate goals include making a map of all protein interactions within a cell, both stable and transient.
Develop improved methodologies for studying protein phosphorylation. An ultimate goal is to define the “phosphoproteome” of an organism.
Develop a tool set for differential proteomics research that includes methods to accurately quantify changes in the levels of proteins and protein modifications.
Development of mass spectrometry as a tool for the atomic resolution structure analysis of proteins, including integral membrane proteins and ion channels.
Development of mass spectrometric informatics tools for the analysis of the proteome. Recently, they are developing tools for annotating the human genome using mass spectrometric information.
They also perform collaborative research in which new mass spectrometric technologies are utilized to assist in the solution of challenging and important biomedical/biological problems. Representative examples (with the names of the major collaborators provided in parenthesis) include studies of control of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel structure and function by phosphorylation, dephosphorylation and ATP hydrolysis (David Gadsby and Angus Nairn); new methods for dissecting the molecular machinery of nucleocytoplasmic transport (Michael Rout and Michael Matunis); cell cycle control in budding yeast and the elucidation of substrates of the major cyclin-dependent kinase in yeast (Frederick Cross and Michael Rout); studies of the pathogenic protozoan Trypanosoma brucei (George Cross); studies aimed at understanding the molecular mechanisms controlling development and dysfunction of the mammalian cerebellum (Nathaniel Heintz); studies of euk
aryotic gene expression and transcription (Robert Roeder); characterization of expression of proteins in the erythrocyte plasma membrane that are encoded by the malaria parasite Plasmodium falciparum (Sanford Simon and Sanjay Desai); investigations of STAT proteins and transciptional regulation (James Darnell); identification of the protein components of human telomeres (Titia de Lange); elucidating the molecular mechanism of transmembrane signal transduction by G protein-coupled receptors (Thomas Sakmar); defining the network of WW domain signaling in yeast (Marius Sudol); understanding the role of opioid receptor systems in addiction and analgesia (Mary Jeanne Kreek); and studies aimed at elucidating the structure and function of ion channels (Roderick MacKinnon).
Brian T. Chait
Camille and Henry Dreyfus Professor
2002年美国化学会国家奖获得者 (ACS 2002 National Award Recipients)
Summary by 杨宏伟 on 2003-12-04
Last updated by 杨宏伟 on 2003-12-04