IDBR: Development of a Linear Ion Trap/Photodissociation Mass Spectrometer for Biological Research

University Of Texas At Austin, Austin TX

Investigators

Abstract

A grant has been awarded to Dr. Jennifer Brodbelt at the University of Texas at Austin to develop a new high performance mass spectrometer for the characterization of biological molecules. Mass spectrometry is currently one of the premier analytical methods for the analysis of biomolecules such as proteins and DNA. Advances in mass spectrometry in recent years have allowed tremendous inroads in the elucidation of, for example, protein biomarkers that characterize nucleic acids responsible for protein synthesis in cells. The ability to solve increasingly complex biological problems depends on improving the performance of mass spectrometers, and the proposed work aims to develop an advanced mass spectrometer that offers better identification of biological molecules and their mutations by using laser-based methods to activate and cleave the biological molecules of interest with high sensitivity. The goal of the project is the design, construction, development and application of a high performance tandem mass spectrometer for the characterization of biological molecules. The core of the instrument is a dual source/linear ion trap/time-of-flight mass spectrometer equipped with two lasers for photodissociation. The heart of the instrument is a linear ion trap which will allow elegant multi-step experiments that incorporate ion isolation for selection of specific ions of interest and photodissociation for disassembly of biological molecules and structural characterization. The project will entail construction of a vacuum chamber, electrical circuits, ion optics, an ionization source, laser options, data acquisition programs, and interfacing of all the components. The mass spectrometer will be built and tested in a modular fashion, and a plan of measurable milestones will be followed. Biological applications involving collaborations will begin in the final year of the project. The new mass spectrometer developed in the grant will allow detailed studies of protein-protein interactions and allow some of the most challenging biological problems to be studied. Nine research groups within the Department of Chemistry and Biochemistry and Institute for Cellular and Molecular Biology at The University of Texas will use the resulting mass spectrometer. The education of future scientists is an equally important goal as accomplishing the scientific objectives stated above. The proposed project will involve the efforts of two graduate students, along with two undergraduate assistants, each year. These students will be trained in the design, development, construction, and testing of state-of-the art analytical instrumentation, will gain experience with the characterization of biological molecules, and will work cooperatively with other graduate students involved on related projects. Due to the interdisciplinary nature of the collaborations, numerous graduate students from other research groups will be exposed to the proposed instrumentation based on teaming with the Dr. Brodbelt?s graduate students to undertake collaborative projects. To increase the awareness of the capabilities of advanced mass spectrometry for solving complex biological problems, PI Brodbelt will offer a mass spectrometry training course at the beginning of each summer term. The course will be publicized to all members of the Department of Chemistry and Biochemistry and Institute for Cellular and Molecular Biology and other local universities.