Life Sciences & Biotechnology
Title : | Understanding the Diversity of Translation Initiation Regulations in Leishmania |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Translation Regulation, Parasitology |
Principal Investigator : | Dr. Nitin Chandrashekhar Tupperwar, CSIR- Centre For Cellular And Molecular Biology (CSIR–CCMB), Hyderabad, Telangana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | nitint@ccmb.res.in |
Details
Executive Summary : | Leishmania species cause a variety of diseases, and there is no commercial vaccine available against them. Anti-Leishmanial drugs often lead to severe toxicities and drug resistance, making clinical management difficult. Understanding the molecular machinery of Leishmania could lead to new drug targets. In Leishmania, there is no evidence of gene expression regulations via conventional transcription activation mechanisms, so post-transcriptional events like mRNA stability and translation are key regulatory elements. Translation regulation is considered the central mechanism driving gene expression in trypanosomatids. In higher eukaryotes, cap-dependent translation is mediated by a cap-binding complex, eIF4F, which is controlled by 4E-binding protein (4E-BP) containing the Y(X4)L element. The genome of Leishmania encodes six paralogs of eIF4E and five paralogs of eIF4G. The absence of 4E-BP and lack of understanding of translation initiation regulation raise questions about cap-binding activities and translation initiation in Leishmania. Using affinity purification and an unbiased proteomics approach, several potential 4E-interacting proteins containing Y(X4)L elements have been identified. The proposed study aims to characterize these potential 4E-interacting proteins, providing insights into translation regulatory mechanisms at the initiation level and potentially identifying new drug targets. |
Total Budget (INR): | 44,75,340 |
Organizations involved