Project description:Mutations in CHCHD10, coding for a mitochondrial intermembrane space protein, are a rare cause of autosomal dominant amyotrophic lateral sclerosis (ALS). Mutation-specific toxic gain of function or haploinsuffuciency models have been proposed to explain pathogenicity. To decipher the metabolic dysfunction associated with the haploinsufficient p.R15L variant we conducted a TMT labelling experiment. Fibroblasts with the CHCHD10 p.R15L variant (hereafter referred to as ‘patient’), were compared to the same cells expressing wild-type CHCHD10 cDNA (hereafter called ‘rescue’) under nutrient stress, in which galactose was substituted for glucose.
Project description:Salmonella causes a range of diseases in different hosts, including enterocolitis and systemic infection. Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. Reversible acetylation in Salmonella Typhimurium depends on acetyltransferase Pat and nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase CobB. Here, we used cell and animal models to evaluate the virulence of pat and cobB deletion mutants in S. Typhimurium, and found that pat is essential for bacterial intestinal colonization, systemic infection and host inflammation response. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA-seq data showed the expression of Salmonella pathogenicity islands 1 (SPI-1) is partially dependent on pat. In addition, we found that HilD is a substrate of Pat, which is essential for maintaining HilD protein level. Taken together, these results suggested that protein acetylation system regulates SPI-1 expression by controlling HilD in a post-translational manner to mediate S. Typhimurium virulence. To use RNA-seq to analyze the transcriptome patterns of pat or cobB mutation in Salmonella Typhimurium 14028s.
Project description:We sought to compare changes in gene expression levels and pathway-level dysregulation between FUS-ALS, sporadic ALS, and healthy control patient derived fibroblasts. Gene expression profiling analysis were performed on bulk RNA-seq data obtained from 12 FUS, 11 sporadic, and 13 healthy control cell lines.
Project description:Salmonella causes a range of diseases in different hosts, including enterocolitis and systemic infection. Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. Reversible acetylation in Salmonella Typhimurium depends on acetyltransferase Pat and nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase CobB. Here, we used cell and animal models to evaluate the virulence of pat and cobB deletion mutants in S. Typhimurium, and found that pat is essential for bacterial intestinal colonization, systemic infection and host inflammation response. Next, to understand the underlying mechanism, genome-wide transcriptome was analyzed. RNA-seq data showed the expression of Salmonella pathogenicity islands 1 (SPI-1) is partially dependent on pat. In addition, we found that HilD is a substrate of Pat, which is essential for maintaining HilD protein level. Taken together, these results suggested that protein acetylation system regulates SPI-1 expression by controlling HilD in a post-translational manner to mediate S. Typhimurium virulence.
Project description:Label-free whole-cell proteomics. Quadruplicates of fibroblast cell lines of healthy control and COA5 mutation carrying patient to investigate complex IV assembly.
Project description:Based on activities of daily living assessments at admission and followed by a 3-month recovery, ischemic stroke participants were categorized into the groups involving the recovery of little effective (LE) and obvious effective (OE). Differentially expressed proteins (DEPs) derived from proteomic testing of the clinical serum samples (5 LE, 5 OE, and 6 healthy control) and differentially expressed genes (DEGs). In total, 194 DEPs (LE vs healthy control) and 174 DEPs (OE vs healthy control) in serum of the enrolled.
