Genetic screening techniques are frequently employed to find the genes responsible for particular biological processes. Forward genetic screens in Caenorhabditis elegans rely on the discovery of mutants that are capable of self-propagating clonal colonies and are thus reproductively active (Zhou et al., 2014). Thus, it is difficult to develop screens that focus on post-reproductive characteristics, including longevity. We accomplish highthroughput automated screening for short-lived mutants utilising protein aggregation as a marker for ageing using microfluidic technology and image processing. Using fluorescently-labeled PAB-1 as a readout, we use microfluidics to undertake repetitive high-throughput analysis and sorting of animals with enhanced protein aggregation as well as to maintain a reproductively active adult mutagenized population (Hermann et al., 1999). We show that longevity mutants may be found without conditional sterilisation or manual separation of the parental and progeny populations by quantitatively analysing fluorescently labelled aggregates and screening for accelerated protein aggregation. We further demonstrate that the aggregate shape of elderly wildtypes and premature aggregation mutants differs; indicating that aggregate growth is time-dependent.
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