Project description:In Drosophila, homozygosity for neoplastic tumor suppressors, like lethal giant larvae, lgl results in malignant transformation of all larval imaginal discs. To gain insight into the molecular players involved in fly tumorigenesis we undertook genome-wide transcriptional profiling of neoplastically transformed wing imaginal discs of lgl mutants. Wild type (Canton S) wing imaginal discs served as control. The transcriptional profile, for instance, revealed the misregulation of JNK and JAK-STAT signaling which is implicated in epithelial transformation in Drosophila. These transcriptional profiles, therefore, provide a useful resource for identification of genes/pathways that are functionally relevant for carcinogenesis.
Project description:Pathogenic bacteria encounter a variety of stressful host environments during infection. Their responses to meet these challenges protect them from deadly damages and aid in adaption to harmful environments. Bacterial products critical for this protection are therefore interesting as suitable targets for new antimicrobials. To shed light on the complex array of molecular pathways involved in bacterial stress responses we challenged 32 diverse human pathogenic bacteria to 11 infection related stress conditions and catalogued their transcriptomes. Initial analyses of the comprehensive data set showed that beside coding RNAs, known and yet unknown putative novel ncRNAs comprise a significant part of the responses. We also computed a scores for all genes to be used for predictions for their probability to be regulated at certain stresses. The core scores enabled identification of universal stress responders representing conserved gene products involved in basic mechanisms important for responses to multiple stresses. Further, the environmental specific core scores made it possible to predict functions of yet non-characterized and also hypothetical gene products. All data are collected in the PATHOGENEX interactive RNA atlas, which is made available to the research community providing ample opportunities for discovering new aspects of regulatory networks in pathogenic bacteria as well as identification of novel players critical for bacterial infectivity and maintenance of infections.
Project description:In this study we applyed transcriptomics and proteomics to brains of mice with systemic hyperammonemia resulting from knockout of hepatic glutamine synthetase to identify new molecular players relevant for ammonia toxicity and hepatic encephalopathy.
Project description:Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal lining of the upper aerodigestive tract and display few treatment options in advanced stages. Despite increased knowledge of HNSCC molecular biology, the identification of new players involved in triggering HNSCC recurrence and metastatic disease is needed. We uncover that G-protein-coupled receptor kinase-2 (GRK2) expression is reduced in undifferentiated, high-grade human HNSCC tumors, whereas its silencing in model human HNSCC cells is sufficient to trigger epithelial-to-mesenchymal transition (EMT) phenotypic features, an EMT-like transcriptional program and enhanced lymph node colonization from orthotopic tongue tumors in mice. Conversely, enhancing GRK2 expression counteracts mesenchymal cells traits by mechanisms involving phosphorylation and decreased functionality of the key EMT inducer Snail1. Our results suggest that GRK2 safeguards the epithelial phenotype, whereas its downregulation contributes to the activation of EMT programs in HNSCC
Project description:Now a days, wound healing is becoming a global threat that impact economy of the country severely. Though the steps involved in wound healing are well characterised, direct therapeutics for the accelerated wound healing is comparatively less. This is solely because of the incomplete mechanism of healing and the lack of knowledge on molecular players involved in wound healing. Hence, in the present study, we have investigated the molecular players involved in wound healing process using a versatile model organism Caenorhabditis elegans through proteomic analyses. Especially, we have employed the high through put proteomic analyses tools such as 2-D GE and LCMS/MS analysis to uncover the molecular players involved in wound healing. As a result of LC-MS/MS analysis at 0 and 24 h, a total of 435 proteins were regulated in both unwounded and wounded conditions in which 13 and 10 proteins were significantly differential regulated. Bioinformatics analyses result suggested that molecular players involved in cortical actin cytoskeleton organization, protein phosphatase binding, and proton transporting ATP synthase activity were identified at 0 h; skeletal muscle myosin thick filament assembly, actin filament depolymerization were identified at 24 h.