Life Sciences & Biotechnology
Title : | Genetic and translational landscape of Candida glabrata pathogenesis for identification of novel antifungal drug targets |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Anil Thakur, Regional Centre For Biotechnology, Haryana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | anil.thakur@rcb.res.in |
Details
Executive Summary : | Candida glabrata is a highly resistant fungal pathogen that can survive in macrophages and replicate within phagosomes, despite being deficient in nutrients and trace elements. It inhibits phagosome maturation and suppresses the production of reactive oxygen species by implementing complex regulatory mechanisms, including global inhibition of protein translation. This inhibition in Saccharomyces cerevisiae is mainly dependent on kinases that phosphorylate the α subunit of GTP bound form translation initiation factor 2 (eIF2), which binds with initiator methionyl-tRNA (Met-tRNAi) in a ternary complex (TC) during scanning of the start codon for translation initiation. The GCN2 kinase is also known to regulate the GCN4 master transcription regulatory factor in Saccharomyces cerevisiae, which activates the general amino acid biosynthesis pathway. The reduction of GCN2 during amino acid starvation decreases the ternary complex and leads to the downstream expression of GCN4 for stress adaptations of S. cerevisiae. The interplay between mRNA translation initiation and decay might be different in C. glabrata compared to S. cerevisiae for stress adaptation and to establish the pathogenicity. Protein translation during stress can be regulated through translation initiation and decay machinery by modulating key players of translation initiation and degradation machinery in a manner distinct from S. cerevisiae or other higher order eukaryotes. This proposal aims to delineate various genetic pathways involved post-transcriptional and translational control of gene regulation contributing to C. glabrata adaptation to highly stressed environments, drug resistance, and pathogenesis. |
Total Budget (INR): | 44,84,832 |
Organizations involved