The Science behind our Research

The ageing chaperome in health and neurodegenerative diseases

Cellular proteostasis is a finely balanced state, where protein production, maintenance, and degradation work harmoniously to preserve cellular well-being. The protein quality control (PQC) system, orchestrated by a network of chaperones (collectively known as the cellular chaperome), plays a central role in upholding this equilibrium. It ensures correct protein folding and prevents the accumulation of misfolded proteins, thereby safeguarding cellular health. Disruptions in proteostasis that surpass the PQC system's capacity can lead to the formation of harmful protein aggregations with irregular structures, potentially causing cellular toxicity and, in severe cases, cell death.

As organisms age, they accumulate intracellular damage, compromising the functional proteome and resulting in cellular dysfunction. Ageing presents increasing challenges in maintaining proteostasis, contributing to the development of diseases such as cancer and neurodegenerative disorders. With the current ageing trend in our population and the rising prevalence of age-related diseases, particularly neurodegenerative disorders, it is imperative to investigate the changes occurring in the ageing chaperome, including the structure and vulnerabilities of organellar PQC subsystems. We firmly believe that these insights will serve as the foundation for future translational medicine interventions.

We postulate that age significantly impacts various aspects of organellar PQC. Ageing is often accompanied by impaired intracellular communication, potentially leading to disruptions in communication pathways between suborganellar PQC systems as individuals age. Our research focuses on unravelling the molecular intricacies underlying the age-related decline of proteostasis and intracellular communication using high-throughput techniques in yeast. Our ultimate goal is to validate and translate these discoveries into more complex eukaryotic model systems.