Chaperonomics, a new tool to study ageing and associated diseases

Area of Science:

• Molecular Biology
• Genomics
• Aging Research

Background:

• Molecular chaperones are crucial for cellular proteostasis and implicated in senescence and age-related diseases.
• Existing knowledge on chaperone gene diversity and number within genomes is incomplete, leading to contradictory findings.
• Eukaryotic chaperone evolution has resulted in complex multi-gene families, complicating functional analysis due to paralogs and differential expression.

Purpose of the Study:

• To develop and present 'chaperonomics', a systematic approach for identifying, characterizing, and classifying chaperone genes and families.
• To enable a comprehensive understanding of chaperone gene composition, evolutionary relationships, and functional properties across different cellular compartments and organisms.
• To provide a foundation for resolving the confusing and contradictory results regarding chaperone roles in aging and disease pathogenesis.

Main Methods:

• Development of concatenated, complementary procedures for genome-wide identification and characterization of chaperone genes.
• Classification of chaperone genes and families based on evolutionary relationships and structural features.
• Application of the chaperonomics framework to the complex heat shock protein 70 (hsp70) gene family as a case study.

Main Results:

• A robust methodology, chaperonomics, has been established for analyzing chaperone gene families in various genomes, including human and model organisms.
• The procedures allow for the elucidation of evolutionary relationships and structural characteristics predictive of chaperone function.
• Illustrative application to the hsp70 family demonstrates the potential of chaperonomics to generate reliable data for future research.

Conclusions:

• Chaperonomics offers a standardized approach to overcome the challenges posed by complex chaperone gene families in eukaryotes.
• This framework is essential for accurately deciphering the roles of specific chaperone genes and their paralogs in cellular processes, development, and disease.
• The data generated through chaperonomics provides a solid foundation for advancing research into the involvement of molecular chaperones in aging and age-related pathologies.