Project description:Emerging evidence suggests that the cryptic translation beyond the annotated translatome may yield proteins with important function. However, the role and function mechanism of these cryptic ORFs in complex diseases such as cancer remain largely unknown. To fill this gap, we combined ribosome profiling and CRISPR/Cas9 screen to systematically identify the colorectal cancer (CRC) dependency on cryptic ORFs.
Project description:Drug resistance is a major public health challenge in Leishmaniasis chemotherapy, particularly in the case of emerging Leishmania/HIV-1 co-infections. Recently, we have delineated the mechanism of cell death induced by the HIV-1 protease inhibitor, Nelfinavir, in the Leishmania parasite. In order to investigate the underlying molecular mechanism involved in Nelfinavir resistance, in vitro Nelfinavir resistant amastigotes were developed by direct drug pressure in culture. RNA expression profiling analyses of closely related Leishmania species were used as a screening tool to compare Nelfinavir-resistant and -sensitive parasites in order to identify candidate genes involved in drug resistance, and several genes were found to be differentially expressed. Comparative gene hybridization (CGH) analyses of Nelfinavir-resistant and -sensitive Leishmania using whole-genome 60-mer oligonucleotide microarrays were also carried out. RNA expression profiles and the CGH of Nelfinavir resistant vs sensitive Leishmania amastigotes suggest that parasites regulate mRNA levels either by modulating gene copy numbers through chromosome aneuploidy, or gene deletion/duplication by homologous recombination. Interestingly, supernumerary chromosomes 6 and 11 in the resistant parasites lead to upregulation of the ABC class of transporters, which are involved in vesicular trafficking. Transporter assays using radiolabeled Nelfinavir suggest that the drug accumulates in greater amounts in the resistant parasites and in a time dependent manner. Furthermore, high-resolution electron microscopy showed an increased number of vacuoles in Nelfinavir-resistant parasites. Together these results suggest that Nelfinavir is rapidly and dramatically sequestered in these intracellular vesicles.
Project description:Hybridization between Cottus rhenanus and C. perifretum has resulted in an evolutionary young hybrid lineage of invasive Cottus that has colonized a new habitat where the parental species are not found (Nolte et al. 2005; Proc. R. Soc. B 272: 2379–2387). This CGH array was designed to screen for copy number variation among Cottus species and to find gene duplicates that are unique to the hybrid lineage (see also Dennenmoser et al. 2017; Copy number increases of transposable elements and protein coding genes in an invasive fish of hybrid origin).
Project description:Identify genes in the epididymal adipose tissue whose expression is under genetic regulation in the hybrid mouse diversity panel. The hybrid mouse diversity panel is comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness. GWAS for expression of epididymal adipose tissue in inbred strains
Project description:Epigenetic mechanisms including histone post-translational modifications control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging aspect of shortened lifespan, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a lifespan screen in S. cerevisiae, designed to identify altered amino acid residues of histones that alter yeast replicative aging. Our results reveal that lack of sustained H3K36 methylation is commensurate with increased cryptic transcription in a set of genes in old cells and shorter lifespan. Deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes and suppresses cryptic transcript initiation to extend lifespan. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to an increase in transcriptional noise that is detrimental to lifespan, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.
Project description:In this study, we used next-generation sequencing technologies and tandem mass tags to characterize mRNA-seq, miRNA-seq and proteomic of Pelteobagrus fulvidraco, P. vachelli and hybrid yellow catfish Huangyou-1 (P. fulvidraco female ×P. vachelli male) livers and in doing so, offer deeper insight into the transcriptional and protein changes in heterosis uncovers key roles for miRNAs.
Project description:Expression profiling analyses for 5 maize inbreds and 4 hybrids, chosen to represent diversity in genotypes and heterosis responses, revealed a correlation between genetic diversity and transcriptional variation. The majority of differentially expressed genes in each of the different hybrids exhibited additive expression patterns, and ~25% exhibited statistically significant non-additive expression profiles. Among the non-additive profiles, ~80% exhibited hybrid expression levels between the parental levels, ~20% exhibited hybrid expression levels at the parental levels and ~1% exhibited hybrid levels outside the parental range. These findings indicate that the frequencies of additive and non-additive expression patterns are very similar across a range of hybrid lines. Keywords: Genotype comparison series