Showing papers by "Lee Murphy published in 2009"

Genomic and genetic analyses of diversity and plant interactions of Pseudomonas fluorescens

Abstract: Pseudomonas fluorescens are common soil bacteria that can improve plant health through nutrient cycling, pathogen antagonism and induction of plant defenses. The genome sequences of strains SBW25 and Pf0-1 were determined and compared to each other and with P. fluorescens Pf-5. A functional genomic in vivo expression technology (IVET) screen provided insight into genes used by P. fluorescens in its natural environment and an improved understanding of the ecological significance of diversity within this species. Comparisons of three P. fluorescens genomes (SBW25, Pf0-1, Pf-5) revealed considerable divergence: 61% of genes are shared, the majority located near the replication origin. Phylogenetic and average amino acid identity analyses showed a low overall relationship. A functional screen of SBW25 defined 125 plant-induced genes including a range of functions specific to the plant environment. Orthologues of 83 of these exist in Pf0-1 and Pf-5, with 73 shared by both strains. The P. fluorescens genomes carry numerous complex repetitive DNA sequences, some resembling Miniature Inverted-repeat Transposable Elements (MITEs). In SBW25, repeat density and distribution revealed 'repeat deserts' lacking repeats, covering approximately 40% of the genome. P. fluorescens genomes are highly diverse. Strain-specific regions around the replication terminus suggest genome compartmentalization. The genomic heterogeneity among the three strains is reminiscent of a species complex rather than a single species. That 42% of plant-inducible genes were not shared by all strains reinforces this conclusion and shows that ecological success requires specialized and core functions. The diversity also indicates the significant size of genetic information within the Pseudomonas pan genome.

Gene Expression Profiles of Endocrine Resistant Breast Tumours.

Abstract: AimTo identify molecular sub-classes of endocrine-resistant breast tumours.MethodsWhole genome expression profiles of 55 endocrine-resistant tumours were obtained using Illumina HT-12 BeadChip arrays. Endocrine resistance was defined as either (i) tumour increased in size during hormonal treatment or (ii) appearance of local recurrence or (iii) contra-lateral breast lesion (metastases or new cancers) during hormonal treatment. Most of the treated patients were post-menopausal. Hormonal treatment included either aromatase inhibitors (letrozole, anastrazole, arimidex) or tamoxifen.ResultsUnsupervised hierarchical clustering using 500 most variable genes split tumours into three major clusters of approximately equal size. The genes discriminating between these clusters included oestrogen receptor- and proliferation- associated set of genes (ESR1, TFF1, TFF3, FOXA1, AGR2, AGR3, XBP1, GATA3, PRAD6B, MYB, CCND1), and stroma-related genes (DCN, COL1A1, COL1A2, COL3A1, COL5A2). Initial analysis of the studied tumours was unable to identify genes associated with clinical features. Sub-division of the dataset may be required to identify these genes more clearly. Genes that tended to separate between tumours resistant to AI and Tamoxifen included MYB, GPR137B, RNF19A, FRMD6, ZNF217 and RPS12. More detailed analysis of the data is underway.DiscussionUnderstanding and overcoming of endocrine resistance will improve treatment results for the majority of breast cancer patients. This abstract reports a new gene expression dataset to compare molecular features of biopsies collected from tumours growing while on endocrine treatment. The initial analysis demonstrates diversity of the resistance mechanisms, enhancing development of individual approaches to endocrine-resistant tumours. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5132.