Periodic Reporting for period 4 - EAGER (Elucidating the effects of ageing on the nucleoporin-directed neural cell type-specific nuclear architecture and gene regulation)
Okres sprawozdawczy: 2022-10-01 do 2024-03-31
Ageing is one of the most critical risk factors for neurological and psychiatric diseases in the developed country. However, the biological links between brain ageing and age-related diseases are still largely unknown. A solid understanding of the cellular biology of neural ageing will be a key to finding the means to treat these diseases. Since neurons in the brain are mostly generated during development with very limited capacity of replacement or renewal, they need to maintain their identity and function throughout our lives. This project aims at seeking a biological link between the fundamental mechanism underlying the long-term maintenance of neural identity and effects of ageing on that.
In the project, we mainly focus on one of nuclear structural proteins, nuclear pore proteins (nucleoporins), which has been postulated as primary target of cellular aging. We specifically test a specific hypothesis that the nucleoporin directed nuclear architecture is a fundamental principle governing cell type-specific gene regulation, and that pathological ageing impairs that regulation. Our preliminary data indicates that one of nucleoporins regulate gene regulation in neurons. To probe how the nucleoporin regulates gene regulation, we are developing molecular and biochemical tools. We also found other nuclear structural protein are dysregulated during aging and impact of brain function. Using novel tools, we will explore how aging impact of nuclear architecture organized by nuclear structural proteins.
Our findings support the original hypothesis that nuclear architecture organized by nuclear structural proteins play critical roles in the maintenance of cell type-specific gene regulation and cellular identity. Using novel tools, we expect to find molecular mechanisms underlying that, which will provide significant insights in neuronal aging and pathological development.