As we've discussed elsewhere [43] , the future of virology depends on making progress in understanding how things work at a systems level, and we must ensure that genomic and proteomic technologies do more than simply generate ever larger quantities of data without providing clues to underlying function. Nevertheless, we are confident that as technologies and experimental systems continue to progress, and data integration strategies become more mature [44] , functional genomics will make ever greater contributions to virology. As an example, we are continuing to take our use of genomics in new directions and Robert Palermo is working together with Marjorie Robert-Guroff (National Cancer Institute) to pursue genomic approaches to improving AIDS vaccine development. Genomic analyses during vaccine trials may reveal gene expression markers of protective immunity or gene expression changes that are indicative of a predisposition to a particular response to immunization and subsequent challenge. All told, the past eight years have been an exciting journey full of discoveries, and we look forward to new breakthroughs in the future. Indeed, life after the Milstein award hasn't been too bad. Representation of the range of viruses and experimental systems we have evaluated using genomic and proteomic technologies. Highlights of experiments related to the use of many of these experimental systems, particularly for hepatitis C virus and influenza, are summarized in this review. SARS-CoV: severe acute respiratory syndrome-associated coronavirus; SIV: simian immunodeficiency virus; WNV: West Nile virus; HIV-1: human immunodeficiency virus type 1; HSV-1: herpes simplex virus type 1; EAM: Expression Array Manager. The Division of Functional Genomics and Infectious Disease provides the virus infection models and the clinical, genomic, proteomic, and immunologic resources needed to perform comprehensive analyses on nonhuman primates. This allows us to analyze the response to virus infection at multiple points along the flow of biological information. EST: expressed sequence tag; AMT: accurate mass and time. Electrospray ionisation-cleavable tandem nucleic acid mass tag–peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS The synthesis and characterization of isotopomer tandem nucleic acid mass tag–peptide nucleic acid (TNT–PNA) conjugates is described along with their use as electrospray ionisation-cleavable (ESI-Cleavable) hybridization probes for the detection and quantification of target DNA sequences by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). ESI-cleavable peptide TNT isotopomers were introduced into PNA oligonucleotide sequences in a total synthesis approach. These conjugates were evaluated as hybridization probes for the detection and quantification of immobilized synthetic target DNAs using ESI-MS/MS. In these experiments, the PNA portion of the conjugate acts as a hybridization probe, whereas the peptide TNT is released in a collision-based process during the ionization of the probe conjugate in the electrospray ion source. The cleaved TNT acts as a uniquely resolvable marker to identify and quantify a unique target DNA sequence. The method should be applicable to a wide variety of assays requiring highly multiplexed, quantitative DNA/RNA analysis, including gene expression monitoring, genetic profiling and the detection of pathogens. Mass spectrometry has much to offer the field of genomic analysis, particularly in terms of multiplexed analysis and accurate quantification. To date, many mass spectrometry-based approaches for genomic analysis have been based on direct detection of nucleic acids particularly using matrix assisted laser desorption ionisation time-offlight (MALDI TOF) MS analysis. MALDI TOF is well suited to this approach due to the high mass range achievable by TOF analysis, however, MALDI TOF instrumentation is relatively expensive and sample preparation can be quite laborious. In addition, direct analysis of nucleic acids by mass spectrometry suffers from problems such as depurination leading to fragmentation (1) or cation adduct formation (2, 3) . These issues notwithstanding, MALDI TOF analysis of nucleic acids has been applied to DNA sequencing (4, 5) , RNA sequencing (6, 7) , analysis of DNA tandem repeats (8) . In particular, PNA probes, with and without noncleavable mass modifiers, have been used for characterization of genomic DNA libraries (9) , detection of DNA methylation (10) and detection of single nucleotide polymorphisms (SNPs) (11, 12) by MALDI TOF mass spectrometry.