Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Epigenetically heritable alteration of fly development in response to toxic challenge

ABSTRACT: Developing organisms have evolved a wide range of mechanisms for coping with recurrent environmental challenges. How they cope with rare or unforeseen challenges is, however, unclear as are the implications to their unchallenged offspring. Here we investigate these questions by confronting the development of the fly, D. melanogaster, with artificial tissue distributions of toxic stress that are not expected to occur during fly development. We show that under a wide range of toxic scenarios, this challenge can lead to modified development which may coincide with increased tolerance to an otherwise lethal condition. Part of this response was mediated by suppression of Polycomb group genes, which in turn leads to de-repression of developmental regulators and their expression in new domains. Importantly, some of the developmental alterations were epigenetically inherited by subsequent generations of unchallenged offspring. These results show that the environment can induce alternative patterns of development that are stable across multiple generations. Measuring differences in RNA levels between larvae that were exposed to a toxic challenge and unchallenged larvae. measuring differences in RNA levels between F3 larvae with or without past exposure to the challenge in F1 generation.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Shay Stern

PROVIDER: E-GEOD-36486 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:One of the key impacts of probiotic bacteria is the ability to beneficially modulate innate and adaptive immune responses of various cell types of the gut-associated lymphoid tissue. In this study we used an in vitro intestinal epithelial cell model to investigate the impact of three probiotic bacteria Lactobacillus helveticus R0052, Bifidobacterium longum subsp. infantis R0033 and Bifidobacterium bifidum R0071 individually, in combination (R0033, R0052 and R0071) and of a specific surface-layer protein partially purified from L. helveticus R0052 (R0052-SLP) in response to a known dsRNA pro-inflammatory stimulus, poly (I:C). Genome-wide human expression microarray chips were used to evaluate other cellular pathways and gain a deeper insight into global gene and pathway modulation. Here we report that the challenge by poly (I:C)-only resulted in the differential expression of 863 genes; whereas, the co-challenge with either R0033, R0052, R0071, R0052-SLP and the multi-strain combination (R0052, R0033 and R0071) resulted in differential expression of 467 genes, 369 genes, 293 genes, 219 genes and 132 genes; respectively. The multi-strain combination had a greater impact than each single component strain at reducing the number of genes modulated. Among the major human pathways modulated by probiotics or R0052-SLP in response to poly (I:C) include: immune/virus, cellular/signaling, nervous/endocrine and autoimmune disorder related pathways. Cytokine and chemokine profiling was performed at the protein level based on specific markers from the TNF-α and NF-KB signaling pathways. The results revealed single strain, multi-strain and R0052-SLP specific attenuation for the majority of proteins measured (TNF-α, IL-8, CXCL1, CXCL2, CXCL10 and IL-10) indicating potentially different mechanisms for each strain, multi-strain and protein component and reinforcing the rationale for multi-strain combinations. The overall study design consisted of 8 different treatments/challenges of HT-29. Briefly, HT-29 cells were co-challenge for 3 h with either the single strains (R0033, R0052 or R0071) or probiotic combination (PC) alone or in combination with poly (I:C) at 10 µg/mL. Also, a specific surface layer protein purified from R0052 (R0052-SLP) was also co-challenged with poly (I:C) in HT-29 cells. Treatment/challenges of poly (I:C)-only, surface layer protein-only (R0052-SLP-only) and probiotic combination-only or PC-only were also evaluated. All challenges and co-challenges were compared to unchallenged control HT-29 cells. 4 biological reps were performed for each of the 8 samples/treatments.

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Epigenetically heritable alteration of fly development in response to toxic challenge

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