Heads of Laboratories
Camille and Henry Dreyfus Professor
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry
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 tools, especially those based on quantitative mass spectrometry, for identifying and studying protein interactions, as well as arriving at a functional definition of cellular protein assemblies. Recently, the laboratory has developed potent tools to elucidate proximal, distal, and transient protein-protein interactions in cellular milieus, as well as tools for determining distance restraints between amino acid residues within large protein assemblies by chemical cross-linking and mass spectrometry. The long-term goal of this research is to develop a molecular microscope for defining cellular systems with scales spanning all the way from dimensions of the cell to atomic resolution of molecules.
The Chait lab also serves as the National Resource for the Mass Spectrometric Analysis of Biological Macromolecules, now in its 42nd 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 using high-capacity traps to produce MS/MS information on all the trapped ion species without the usual scanning losses. The lab is also developing novel instrumentation for carrying out massively parallel mass spectrometry.
Another aim of the lab is to develop new methods to study viral-host 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.
Most recently, the lab has 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. They have also developed a new method for improving the sensitivity of electrospray ionization mass spectrometers.
B.Sc. in natural sciences, 1969
B.Sc. in physics, 1970
University of Cape Town
D.Phil. in nuclear physics, 1976
University of Oxford
University of Manitoba, 1977–1979
Research Associate, 1979–1981
Assistant Professor, 1981–1985
Associate Professor, 1985–1991
The Rockefeller University
Newcombe-Cleveland Prize, 1998
Bijvoet Medal, Utrecht University, 2000
Frank H. Field and Joe L. Franklin Award, American Chemical Society, 2002
HUPO Discovery Award in Proteomics Sciences, 2007
Pehr Edman Award, 2012
Distinguished Contribution Award, American Society for Mass Spectrometry, 2015
Krutchinsky, A.N. et al. Maximizing ion transmission from atmospheric pressure into the vacuum of mass spectrometers with a novel electrospray interface. J. Am. Soc. Mass Spectrom. 26, 649–658 (2015).; Krutchinsky, A.N. et al. Optimizing electrospray interfaces using slowly diverging conical duct (ConDuct) electrodes. J. Am. Soc. Mass Spectrom. 26, 659–667 (2015).
Fridy, P.C. et al. A robust pipeline for rapid production of versatile nanobody repertoires. Nat. Methods 11, 1253–1260 (2014).
Shi, Y. et al. Structural characterization by cross-linking reveals the detailed architecture of a coatomer-related heptameric module from the nuclear pore complex. Mol. Cell Proteomics 13, 2927–2943 (2014).
Subbotin, R. and Chait, B.T. A pipeline for determining protein-protein interactions and proximities in the cellular milieu. Mol. Cell Proteomics 13, 2824–2835 (2014).
Scheid, J.F. et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633–1637 (2011).
Dr. Chait is a faculty member in the David Rockefeller Graduate Program, the Tri-Institutional M.D.-Ph.D. Program, and the Tri-Institutional Ph.D. Program in Chemical Biology.