Functional genomics by mass spectrometry

Systematic analysis of the function of genes can take place at the oligonuc leotide or protein level. The latter has the advantage of being closest to function, since it is proteins that perform most of the reactions necessary for the cell. For most protein based ('proteomic') approaches to gene func tion, mass spectrometry is the method of choice. Mass spectrometry can now identify proteins with very high sensitivity and medium to high throughput. New instrumentation for the analysis of the proteome has been developed in cluding a MALDI hybrid quadrupole time of flight instrument which combines advantages of the mass finger printing and peptide sequencing methods for p rotein identification. New approaches include the isotopic labeling of prot eins to obtain accurate quantitative data by mass spectrometry, methods to analyze peptides derived from crude protein mixtures and approaches to anal yze large numbers of intact proteins by mass spectrometry directly. Example s from this laboratory illustrate biological problem solving by modern mass spectrometric techniques. These include the analysis of the structure and function of the nucleolus and the analysis of signaling complexes, (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Scienc e B.V. All rights reserved.