Project description:Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and integrated multi-omics data set (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application. Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and integrate the single data sets will be described. In summary, we present temporal and integrated multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool to provide a searchable transcriptome and proteome for kidney fibrosis researchers.
Project description:(i) To determine the inhibitory effect of Luvangetin against Fusarium verticillioides and fumonisins production in vitro and in vivo, and (ii) to investigate the mode of action of Luvangetin against Fusarium verticillioides by transcriptomics and proteomics analysis.
Project description:Salicylic acid (SA) is one of the key signal molecules in regulating plant resistance to diverse pathogens. It is predominantly associated with resistance against biotrophic and hemibiotrophic pathogens, and triggering systemic acquired resistance (SAR) in Arabidopsis. However, whether and how SA directly affects Fusarium graminearum and how SA influences the defence efficiency of wheat against fusarium head blight (FHB) are still poorly understood. Previous experiments have shown that the growth of F. graminearum mycelia and the germination of spores were significantly inhibited, and eventually stopped by increasing amounts of SA in both liquid and solid media cultures. Co-inoculation of SA and Fg spores has led to reduced FHB symptoms in the very susceptible Triticum aestivum cultivar ‘Roblin’. To better understand the effect of SA on F. graminearum mycelial growth, we have compared the expression profiles of SA-treated and untreated F. graminearum liquid cultures after 8 and 24 h of treatment, using an F. graminearum custom-commercial microarray. The microarray analysis suggests that F. graminearum can metabolize SA through two pathways, the gentisate and catechol pathways that are present in many fungal species. Additional experiments have confirmed the capacity of F. graminearum to metabolize SA. Our results demonstrate that, although F. graminearum has the capacity to metabolize SA, SA has a significant and direct impact on F. graminearum through a reduction in efficiency of germination and growth at higher concentrations. Untreated and Salicylic Acid (SA) treated liquid cultures of F. graminearum at 8h and 24h collection times. Three biological replicates per time point and treatment, 2 technical replicates (dye flips) per sample.
Project description:Role of fungal cellulases upon Fusarium oxysporum infection. We obtained Fusarium oxysporum mutants, which cannot degrade cellulose capacity to observe their virulence. Cellulose degradation is not mandatory for Fusarium oxysporum to reach the plant vasculature system.
Project description:Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease. Its pathological aggregation can be mitigated by tramiprosate and its metabolite 3-sulfopropanoic acid, along with their impact on the transcription of genes, expression of proteins, and production of lipids. Taurine (TRN) is a close chemical analogue of tramiprosate (TMP) with an extra carbon atom , demonstrating protective effects against aging. Using an integrated approach involving static light scattering, hydrogen-deuterium exchange mass spectrometry, molecular dynamics, and studies of cerebral organoids, we evaluated the effects of 3-sulfopropanoic acid and taurine on ApoE4 aggregation, as well as their impact on organoid transcriptomics and proteomics. Our results reveal that taurine effectively inhibits ApoE4 aggregation, comparable to 3-sulfopropanoic acid, and ameliorates the pathophysiological phenotype of ApoE4 in cerebral organoids, aligning it more closely with the ApoE3 phenotype. These findings suggest that taurine may have potential as a therapeutic agent against Alzheimer's disease, particularly in ApoE4/E4 carriers.
Project description:The target of rapamycin (TOR) kinase is a central signaling hub that plays a crucial role in precisely orchestrating plant growth and development. It is increasingly evident that TOR also has a significant impact on plant stress responses. This suggests that TOR is intricately involved in maintaining the balance between plant growth and stress responses. Nevertheless, despite the observed effects, the specific mechanisms through which TOR operates in these processes remain obscure. In this study, we investigated how the tomato (Solanum lycopersicum) TOR (SlTOR) affects plant growth and cold responses. We demonstrated that the inhibition of SlTOR transcriptionally primes cold stress responses, consequently enhancing tomato cold tolerance. Furthermore, a widely targeted metabolomics analysis revealed the disruption of amino acid metabolism homeostasis under cold stress upon SlTOR inhibition. This disruption led to the accumulation of two important defense metabolites: salicylic acid (SA) and putrescine (Put). Subsequent gain- and loss-of-function analyses validated the crucial roles of salicylic acid and putrescine in enhancing tomato cold tolerance. Our study provides a mechanistic framework that elucidates how SlTOR modulates amino acid-related metabolism to enhance tomato cold tolerance, which sheds light on the complex interplay between growth and stress responses orchestrated by TOR.
Project description:Investigation of whole genome gene expression level changes over time of Fusarium verticillioides wild-type in liquid fumonisin inducing media (GYAM). Fusarium verticillioides produces a polyketide derived mycotoxin, fumonsin, over time in liquid media (Proctor et al, Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic gene cluster in Gibberella moniliformis, Fungal Genetics and Biology, 38:237-249).
Project description:Investigation of whole genome gene expression level changes over time of Fusarium verticillioides wild-type in liquid fumonisin inducing media (GYAM) Fusarium verticillioides produces a polyketide derived mycotoxin, fumonsin, over time in liquid media, Proctor et al, Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic gene cluster in Gibberella moniliformis, Fungal Genetics and Biology, 38:237-249
Project description:Investigation of whole genome gene expression level changes over time of Fusarium verticillioides wild-type in liquid fumonisin inducing media (GYAM). Fusarium verticillioides produces a polyketide derived mycotoxin, fumonsin, over time in liquid media (Proctor et al, Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic gene cluster in Gibberella moniliformis, Fungal Genetics and Biology, 38:237-249). A twelve chip study using total RNA recovered from twelve wild type cultures of Fusarium verticillioides. Each chip measures the expression level of 13,288 genes with thirteen 60-mer probe pairs per gene.