Proteomics is increasingly employed in both neurological and oncological research to provide insight into the molecular basis of disease but rarely has a coherent, novel pathophysiological insight emerged. Gliomas account for >50% of adult primary intracranial tumors, with malignant gliomas (anaplastic astrocytomas and glioblastoma multiforme) being the most common. In glioma, the application of proteomic technology has identified altered protein expression but without consistency of these alterations or their biological significance being established. A systematic review of multiple independent proteomic analyses of glioma has demonstrated alterations of 99 different proteins. Importantly 10 of the 99 proteins found differentially expressed in glioma [PHB, Hsp20, serum albumin, epidermal growth factor receptor (EGFR), EA-15, RhoGDI, APOA1, GFAP, HSP70, PDIA3] were identified in multiple publications. An assessment of protein-protein interactions between these proteins compiled using novel web-based technology, revealed a robust and cohesive network for glioblastoma. The protein network discovered (containing TP53 and RB1 at its core) compliments recent findings in genomic studies of malignant glioma. The novel perspective provided by network analysis indicates that the potential of this technology to explore crucial aspects of glioma pathophysiology can now be realized but only if the conceptual and technical limitations highlighted in this review are addressed.

Bacterial two-component regulatory systems (TCS) are common components of complex regulatory networks and cascades. In Sinorhizobium meliloti, the TCS ExoS/ChvI controls exopolysaccharide succinoglycan production and flagellum biosynthesis. Although this system plays a crucial role in establishing the symbiosis between S. meliloti and its host plant, it is not well characterized. Attempts to generate complete loss-of-function mutations in either exoS or chvI in S. meliloti have been unsuccessful; thus, it was previously suggested that exoS or chvI are essential genes for bacterial cell growth. We constructed a chvI mutant by completely deleting the open reading frame encoding this gene. The mutant strain failed to grow on complex medium, exhibited lower tolerance to acidic condition, produced significantly less poly-3-hydroxybutyrate than the wild type, was hypermotile, and exhibited an altered lipopolysaccharide profile. In addition, this mutant was defective in symbiosis with Medicago truncatula and M. sativa (alfalfa), although it induced root hair deformation as efficiently as the wild type. Together, our results demonstrate that ChvI is intimately involved in regulatory networks involving the cell envelope and metabolism; however, its precise role within the regulatory network remains to be determined.

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