Mass Spectrometry: Reconnaissance at the Frontiers of Biology

The 10th International Symposium on Mass Spectrometry in the Health and Life Sciences: Molecular and Cellular Proteomics was held in San Francisco in August 2011. This biennial event has become one of the premier meetings on the proteomics agenda. As with its predecessors, this symposium was designed to showcase how mass spectrometric-based technology has developed into one of the most important tools to address the challenges of unraveling complex biological problems. The articles contained in this special issue of Molecular & Cellular Proteomics are a representative sampling of the presentations and illustrate both the technical advances and the practical applications of mass spectrometry to proteomic analyses in the past 2 years. These are, of course, often mixed together: new technological developments being described in terms of the investigation of biological questions. Three articles (presenters at the meeting are indicated by brackets) describe improved developments with existing methodology, particularly as it relates to quantification of both proteins and post-translational modifications: Deeb et al., 77–89 [Mann] used super-SILAC for the classification of diffuse large B-cell lymphoma subtypes, Stokes et al., 187–201 [Silva] describe the identification and quantification of peptides from critical signaling proteins by immunoaffinity enrichment coupled with LC-MS/MS (PTMScan Direct), and Peach et al., 128–137 [Jaffe] illustrate the use of chromatin immunoprecipitation-grade antibodies in the quantitative assessment of histone modifications. There were also several talks that focused directly on post-translational modifications as the mediators of intracellular signaling events. Three of these dealt with phosphoproteome analyses and are represented by the contributions of Biarc et al., 15–30 [Bradshaw], who used TrkA-chimeric receptors to determine downstream phosphorylations of serine and threonine protein substrates following growth factor stimulation; Franz-Wachtel et al., 160–170 [Macek], who report protein kinase D-dependent phosphorylation events in nocodazole-treated human cells; and Ruperez de Arrilucea et al., 171–186 [Ruperez], who provide a quantitative phosphoproteomic analysis that identifies serine and threonine kinase involvement in the cytoskeletal reorganization in early T-cell receptor activation in human primary T-cells. Two other articles describe modifications of lysine side chains. Xie et al., 100–107 [Zhao] report on the rarer succinylation and malonylation additions, whereas Udeshi et al., 148–159 [Udeshi] describe the much more prevalent ubiquitination modification, which, along with acetylation, is rapidly challenging the O-modifications of serine and threonine in terms of extent of diversification and importance. Moreover, as post-translational modification analyses have become increasingly prevalent and extensive, software able to analyze this information has become more and more critical. Chalkley and Clauser, 3–14 [Chalkley] summarize the state of programs to localize post-translational modifications in their timely review, and Schilling et al., 202–214 [Gibson] discuss the use of the Skyline software tool in the platform-independent and label-free quantification of proteomic data of MS1 extracted ion chromatograms as applied to protein acetylation and phosphorylation data. The remainder of the articles are devoted to the analyses of various enzymes, paradigms, and systems. Suganuma et al., 90–99 [Workman] report on a metazoan Two A containing (ATAC) acetyltransferase subunit, which is related to an ancient molybdopterin synthase component that regulates mitogen-activated protein kinase signaling, and Rutger et al., 47–59 [Hertz] describe a chemical genetic approach for human aurora B kinase to identify novel substrates of the chromosomal passenger complex. Tsai et al., 60–76 [Cristea] used functional proteomics to establish the interaction of SIRT7 with chromatin remodeling complexes, giving greater insight into its role in regulating RNA polymerase I transcription, and Tetenbaum-Novatt et al., 31–46 [Rout] give a report on a role for nonspecific competition in karyopherin-nucleoporin interactions in nucleocytoplasmic transport. Two other contributions delved into more complex systems: Fang et al., 138–147 [Huang] report a label-free strategy to map the protein interaction network of the human COP9 signalosome complex, and Hastie et al., 108–127 [Gorman] discuss the regulation of the type I and II interferon pathways by the human respiratory syncytial virus nonstructural protein 1, an important pathogen affecting young children. This selection of papers (from the several dozen presented orally or in posters) gives an excellent flavor of not only the symposium but the field in general. The unbiased nature of mass spectrometric analyses is proving to be enormously useful in defining the myriad of signaling events (manifested in a wide variety of post-translational modifications) and thus identifying the players and their interactions that characterize living cell responses. However, there has over the last 10 years also been a steady shift from broad unfocused analyses, to those that more closely probe specific situations, which reflect normal and pathological responses/conditions. Many of the technical advances have been introduced with this sharpening of focus in mind. All of this reflects the essential balance between understanding basic biology, determining translatable goals, and the development of usable diagnostics/therapeutics/prophylactics to treat the human condition. Thus the symposium is moving and changing with the times as it keeps abreast of these shifts. It will be exciting to see how these changes are further manifested in the 11th Symposium in 2013.