Research

Life Sciences & Biotechnology

Title :

Elucidation of the kinetochore architecture in a basidiomycetes yeast Cryptococcus neoformans

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Kaustuv Sanyal , Jawaharlal Nehru Centre For Advanced Scientific Research, Karnataka

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Equipments :

Details

Executive Summary :

High-fidelity chromosome segregation is crucial for the successful transfer of genetic information in eukaryotes. The mechanism of chromosome segregation is dependent on cellular processes involving physical interaction between centromeric chromatin, kinetochore, and microtubules. The kinetochore is organized as a multi-layered complex, encompassing an inner and outer kinetochore, each with its own subunit complexes. Organisms in phylum Basidiomycota stand apart for the loss of CCAN proteins and the unique ordered assembly of outer and inner kinetochore proteins. The fully assembled kinetochore is observed as a single puncta only upon the onset of mitosis, while the preceding cell cycle stages possess unclustered centromeres. This temporal organization of kinetochore proteins across cell-cycle stages makes it an appropriate model to investigate kinetochore organization dynamics and architecture. Previous studies have identified a novel unconventional linker protein bridgin (Bgi1), which localizes to the outer kinetochore Knl1C-Mis12C-Ndc80C (KMN) complex and links to centromeric chromatin using a basic charged domain. This suggests the presence of additional proteins that can potentially complement the loss of CCAN proteins in C. neoformans and other related species of Basidiomycota. The study of this unique kinetochore design is interesting from a clinical point of view, as C. neoformans tops the critical priority group of fungal pathogens and has emerged as a potential threat to humans due to its antifungal resistance. Identifying Basidiomycota-specific proteins from the kinetochore interactome might serve as potential antifungal drug targets with high specificity and minimal side effects.

Total Budget (INR):

70,82,726

Organizations involved