Heads of Laboratories
Mass spectrometry is a powerful analytical technique that can accurately measure the molecular masses of individual biomolecules, including peptides, proteins and large intact protein assemblies. Dr. Chait’s laboratory specializes in the development of mass spectrometers and other tools and methods for investigating a variety of biological and biochemical phenomena.
Knowledge of the makeup, structure and dynamics of protein assemblies is key to understanding many cellular processes. A central focus of the Chait lab has been the development of novel mass spectrometers and biochemical tools, especially those based on quantitative mass spectrometry, for identifying and studying protein interactions and applying these tools to arrive at a functional definition of cellular protein assemblies. The long-term goal of this research is to develop a multiscale molecular microscope for defining cellular systems in which the scales span all the way from dimensions of the cell to atomic resolution of the molecular players.
The Chait lab also serves as the National Resource for the Mass Spectrometric Analysis of Biological Macromolecules, now in its 40th year of funding from the National Institutes of Health. Its major areas of activity are basic research in mass spectrometry and ion chemistry. Work is currently under way in Dr. Chait’s lab to develop novel tandem mass spectrometry (MS/MS) instrumentation for ultrasensitive, rapid and comprehensive characterization of proteins. Most MS/MS is inherently extremely wasteful, since, at any given time, all ion species except for the one that is specifically isolated are thrown away. The Chait lab is investigating new strategies for overcoming this inefficiency by capturing ions in novel high-capacity ion traps, in which they are cooled and sequentially ejected at increasing m/z ratios. Each of the ejected ions is fragmented, producing MS/MS information on all the trapped ion species without the usual scanning losses. The lab is also developing instrumentation for massively parallel mass spectrometry.
Another aim of the lab is to develop new methods to study viralhost protein interactions during the progression of the highly dynamic viral infection. In particular, members of the Chait lab are developing techniques for simultaneously visualizing individual viral proteins in host cells and identifying their interacting macromolecular partners in space and time. Some of these techniques are already facilitating a greater understanding of both the molecular details of viral infections and the biology of the cell.
In collaboration with Rockefeller’s Nathaniel Heintz, work also is under way to unravel the molecular synaptic code in the mammalian brain. The formation of a functional brain requires several steps from the generation of numerous types of neurons through the establishment of a very precise connectivity among those neurons. The Chait and Heintz labs aim to identify the composition of individual synapses from specific neuronal populations and compare those compositions with one another. They have developed methods that enable them to elucidate those different synaptic compositions.
Dr. Chait and his colleagues are also working toward developing a set of tools that will allow them to analyze chromatin in unprecedented detail. Specifically, they would like to be able to take any portion of a given chromosome under specified cellular conditions and define where the nucleosomes are positioned, quantitate the site-specific modifications on the histones making up those nucleosome and define the position and makeup of every protein and protein complex that is resident on the particular piece of chromatin. Ultimately, their goal is to better understand the sets of proteins that associate with any given region of a chromosome and how they are arranged upon the DNA sequence. Most recently, they have developed new mass spectrometric techniques for defining repertoires of high-affinity antibodies that develop within humans (and llamas) against any given antigen, including endogenous human antibodies that are protective against HIV.
Dr. Chait is a faculty member in the Tri-Institutional Ph.D. Program in Chemical Biology.
Dr. Chait received his B.Sc. in 1969 and his B.Sc. Hons. in 1970, both from the University of Cape Town, in South Africa, and his D.Phil. in 1976 from the University of Oxford. He did postdoctoral research at the University of Manitoba and joined Rockefeller in 1979 as a research associate in Frank H. Field’s laboratory. He was appointed assistant professor in 1981, associate professor in 1985 and professor in 1991. In 1995, he was named the Camille and Henry Dreyfus Professor.
His awards include the 2012 Pehr Edman Award, the 2007 HUPO Discovery Award in Proteomics Sciences, the 2002 Frank H. Field and Joe L. Franklin Award for Outstanding Achievement in Mass Spectrometry from the American Chemical Society, the 2000 Bijvoet Medal from Utrecht University and the 1998 American Association for the Advancement of Science Newcombe-Cleveland Prize. He has been awarded 23 United States patents for his inventions.
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