Project description:Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination of this neglected tropical disease. Here we conducted whole genome resequencing, proteome profiling, and comparative analyses of a drug-resistant clinical isolate and two drug-susceptible strains of Leishmania donovani to explore genetic features that might contribute to the establishment of drug resistance in this parasite. By comparative genomic analysis, exclusive variations were identified in the drug-resistant isolate of L. donovani, including 86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes. Comparative proteomic analysis indicated significant differences in protein expression between resistant and susceptible strains of L. donovani, including 69 exclusive detected molecules and 84 consistent down-/up-regulations in the former. Integrating the genomic mutations and proteomic specificities linked nine of the genomic mutations (gene duplication, insertion and deletion) to significantly altered protein expression changes in the drug-resistant clinical isolate. These genetic features were inferred to be associated with nucleotide-binding and fatty acid metabolism (biosynthesis and degradation), which might contribute to fitness-gains allowing for the drug-resistant phenotype of L. donovani. This comparative and integrative work provided deep insights into the molecular basis underlying resistance establishment, suggesting new aspects to be investigated for novel intervention strategies against L. donovani and related species.
Project description:IL28B genotype was shown to be associated with treatment outcome of antiviral thearpy for HCV infection. We tried to clarify the molecular feature that was asocciated with IL2B genotype by comparing Hepatic gene expression of HCV related Hepatocellular carcinoma and non-cancerous tissue with Il28B rs8099917 TT genotype and TG/GG genotype.
Project description:A miRNA microarray was performed from HCV infected patient serum samples of bothe genotype 1b and genotype 3a, which are prevalent in India, with the aim of identifying a set of miRNAs which are uniquely differentially expressed during HCV infection. miR-320c, miR-483-5p, miR-134 and miR-198 were found to be upregulated in the patient samples as compared to the controls and are currenty being validated.
Project description:Our aim is to analyze the genome of human melanoma cell lines and short term culture from human melanoma samples in order to identify genes that confer drug resistance to clinically relevant targeted therapies. We will perform whole-exome sequencing, copy number variation analysis and methylome analysis in a collection of human melanoma cell lines and short term culture that will be then screened for drug sensitivity/resistance through a library of clinically relevant drugs and drug combinations. By the combined analysis of the genomic lesion and the drug sensitivity/resistance profile of different cell lines, we will look for genes whose mutation is associated to the sensitivity or resistance to a specific drug in different samples.
