Identifying C. elegans lifespan mutants by screening for early-onset protein aggregation

Area of Science:

• Genetics
• Molecular Biology
• Biotechnology

Background:

• Forward genetic screens in *Caenorhabditis elegans* typically require reproductively active mutants.
• Screening for post-reproductive phenotypes like lifespan is challenging due to the need for self-propagating populations.
• Protein aggregation is a known marker associated with aging processes.

Purpose of the Study:

• To develop a high-throughput screening method for identifying short-lived mutants in *C. elegans*.
• To utilize microfluidics and image processing for automated screening of aging phenotypes.
• To establish protein aggregation as a reliable marker for identifying lifespan mutants.

Main Methods:

• Combined microfluidic technologies with image processing for automated screening.
• Used microfluidics to maintain a reproductively active mutagenized population.
• Employed fluorescently-labeled PAB-1 as a readout for protein aggregation and sorted animals accordingly.

Main Results:

• Successfully identified lifespan mutants by screening for accelerated protein aggregation.
• Demonstrated that quantitative analysis of fluorescent aggregates can identify mutants without conditional sterilization.
• Observed differences in aggregate morphology between aged wildtypes and premature aggregation mutants, indicating time-dependent aggregate growth.

Conclusions:

• High-throughput microfluidic screening is effective for identifying lifespan mutants in *C. elegans*.
• Protein aggregation serves as a viable marker for aging and lifespan studies in automated genetic screens.
• Aggregate morphology analysis can provide insights into the time-dependent nature of protein aggregation during aging.