Project description:We determined the set of newly acquired CRISPR spacers during naive and primed adaptation in E. coli. We compared primed adaptation when targeting different plasmid and chromosomal sites. These data provide insight into the sequence features that impact the efficiency of primed adaptation in E. coli.
Project description:Caloric restriction extends lifespan, an effect once thought to involve attenuation of reactive oxygen species (ROS) generated by aerobic metabolism. However, recent evidence suggests that caloric restriction may in fact raise ROS levels, which in turn provides protection from acute doses of oxidant through a process called adaptation. To shed light on the molecular mechanisms of adaptation, we designed a series of genome-wide deletion fitness screens to identify genes involved in adaptation to hydrogen peroxide.
Project description:The mechanism of evolution in different conditions can be examined from various molecular aspects that constitute a cell, namely, transcript, protein or metabolite abundance. We have analyzed transcript and metabolite abundance changes in evolved and ancestor strains in three different evolutionary conditions, namely, excess-nutrient adaptation, prolonged stationary phase adaptation and adaptation due to environmental shift, in two different strains of Escherichia coli K-12 (MG1655 and DH10B).
Project description:Adaptation to hydrogen peroxide in Saccharomyces cerevisiae is profiled with expression arrays. Adaptation describes the process in which a mild dose of toxin (in this case, hydrogen peroxide) is able to protect against a later acute dose. Here, we study two adaptive protocols (0.1 mM H2O2 and 0.1 + 0.4 mM H2O2) and one acute protocol (0.4 mM H2O2) to identify processes uniquely involved in adaptation. Predictions from these studies are validated in expression profiling of deletion mutants of the transcription factors Yap1, Mga2, and Rox1.
Project description:Intervention group:Virtual-reality based Cognitive Behavioral Intervention ;Attention Control group:Dietary guidance
Primary outcome(s): The sick role adaptation
Study Design: Parallel
Project description:This study evaluates genetic and phenotypic variation in the high altitude Colla population living in the Argentinean Andes above 3500 m. They were compared to the Wichí population living in the nearby lowlands of the Gran Chaco region. This study attempts to pinpoint evolutionary mechanisms underlying adaptation to hypobaric hypoxia. We have genotyped 25 individuals from both populations for 730,525 SNPs.
Project description:High-altitude adaptation is a representative example of vertebrates getting adapted to harsh and extreme environments. To investigate the miRNA expression alterations of goats that were induced by high altitude stress, we performed comparative miRNA transcriptome analysis on six hypoxia-sensitive tissues (heart, kidney, liver, lung, skeletal muscle and spleen) in two indigenous goat populations from distinct altitudes (600 m and 3000 m). We obtained the expression of 1391 mature miRNAs and identified 138 differentially expressed miRNAs between altitudes. Combined with tissue specificity analysis, we illustrated alterations of expression levels between altitudes and among tissues, which suggested the coexisting tissue-specific and tissue-conserved mechanism for hypoxia adaptation. Notably, the interplay between DE miRNA and DE target genes strongly indicated post-transcriptional regulation in HIF-1 signaling pathway, insulin signaling pathway and p53 signaling pathway, which might play a significant role in high altitude adaptation in domestic goats. These results provide insights into the complicated miRNA expression pattern and regulatory mechanism of high altitude adaptation in domestic goats.
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. In addition to genetic mutations, recent research has identified a role for non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell-state transitions that occur in the adaptation to cancer therapies remain unknown and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell-state transitions accompanied by a progressive increase in cell fitness, which we denote as the 'resistance continuum'. This cellular adaptation involves a stepwise assembly of gene expression programmes and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that epithelial-to-mesenchymal transition or stemness programmes-often considered a proxy for phenotypic plasticity-enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify the acquisition of metabolic dependencies, exposing vulnerabilities that can potentially be exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell-state transitions.
Project description:Using Caenorhabditis elegans to investigate environmental cues-induced mitochondrial dysfunction, we found that exposure to electron transport chain (ETC) inhibitors at the parental generation initiates the transmission of heritable information to descendants and make descendants stress-adaptive. This mitochondrial stress adaptation phenotype can persist for at least three generations. Animals lacking histone H3K4me3 chromatin modifiers, or the methyltransferase of N6-methyldeoxyadenosine (6mA), lose the ability to initiate stress adaptation in progeny. H3K4me3 plays a role upstream of 6mA, while both mark promoter regions of mitochondrial unfolded protein response (UPR mt ) genes and activate the UPR mt pathway to alleviate mitochondrial damage.
Project description:<p>Due to a unique adaptation to high altitude, the Tibetan Plateau population has been the subject of much research interest. In this study, we conducted whole genome sequencing of 27 Tibetan individuals. Through our analysis, we inferred a detailed history of demography and revealed the natural selection of Tibetan population. We provided evidence of genetic separation between the two subpopulations of Han and Tibetans as early as 44 to 58 thousand years ago, replicated previously reported high altitude adaptation genes, including <i>EPAS1</i> and <i>EGLN1</i>, and reported three new candidate genes, including <i>PTGIS</i>, <i>VDR</i>, and <i>KCTD12</i>.</p>