Brian T. Chait, D.Phil.
Camille and Henry Dreyfus Professor
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry
E-mail: chait@rockefeller.edu
Mass spectrometry is a powerful analytical technique that can accurately measure the molecular weights of individual biomolecules, such as proteins and nucleic acids, and determine their structures. Dr. Chait’s laboratory specializes in the use of mass spectrometry as a tool for investigating properties and reactions of gaseous ions, the phenomena involved in ionization processes such as laser desorption ionization and electrospray ionization, and a variety of biological and biochemical phenomena.
Knowledge of the makeup, structure and dynamics of protein assemblies is a key to the understanding of many cellular processes. Thus, a central focus of the Chait laboratory has been the development of biochemical tools (especially mass spectrometry-based tools) for studying protein interactions and the application of these tools for the elucidation and functional definition of cellular protein assemblies. Although currently available tools are already revolutionizing aspects of biological research, further improvements are highly desirable.
Over the years, the Chait lab has developed robust mass spectrometric methods for accurately elucidating the domain structures of recombinant proteins, which have proven invaluable for x-ray crystallographic structure determinations. Recently, Dr. Chait and his colleagues developed a new variation of the limited proteolysis method, which they named protease accessibility laddering (PAL), which allows them to elucidate the domain structures of proteins expressed at endogenous levels.
For the last 34 years, the Chait lab has also served as the National Resource for the Mass Spectrometric Analysis of Biological Macromolecules funded by the National Institutes of Health, and, as such, its major areas of activity are basic research in mass spectrometry and ion chemistry and collaborative research involving mass spectrometry and various biomedical disciplines. Work is currently under way in Dr. Chait’s lab to develop novel tandem MS (MS/MS) instrumentation for ultrasensitive, rapid and comprehensive characterization of proteins. Most tandem mass spectrometry 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 a new strategy for overcoming this inefficiency by capturing ions in a novel high capacity ion trap, cooling these ions in the trap, sequentially ejecting the trapped ions at increasing m/z ratios and fragmenting each of these ejected ions in turn, thereby producing MS/MS information on all the trapped ion species, without the usual scanning losses.
Another aim of the lab is to develop new methods to study viral-host and viral-viral 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. These techniques promise to greatly facilitate understanding of both the molecular details of viral infections and the biology of the cell.
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 between these neurons. The Chait lab aims to identify the composition of individual synapses from specific neuronal populations and compare these compositions with one another. The goal of this project is to develop a method that will enable them to elucidate these different synaptic compositions.
Dr. Chait and his colleagues also are 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 these nucleosomes and define the position and makeup of every protein and protein complex that is resident on this particular piece of chromatin. Ultimately, their goal is to elucidate the sets of proteins that associate with any given region of a chromosome, and how they are arranged upon the DNA sequence.
CAREER
Dr. Chait received his B.Sc. in 1969 and his
B.Sc. Hons. in 1970, both from the University
of Cape Town, 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 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 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 20 U.S. patents for his inventions.
