HAPPY Screening

In the phase of pre-clinical drug development (or re-purposing), good research models are required. To confer suitability upon a model system for the study of aging, two characteristics are essential: The model needs to be relevant (reflect the hallmarks of aging) and it must be readily amenable.

The single-cell organism Saccharomyces cerevisiae possesses both qualities.

First, the majority of hallmarks of the aging present in vertebrates also manifest themselves in replicative aging yeast. It is thus not surprising, that S. cerevisiae has been an important model for studying the molecular mechanisms of aging in eukaryotic cells for almost two decades. It has played a pivotal role in the understanding of basic cellular processes such as cell cycle regulation, intracellular trafficking, protein folding regulation, and many others.

Second, yeast has some surprising similarities (homologues and orthologues) with mammalian (including human) cells, which makes it effective to model human diseases.

Third, yeast has a short generation time, convenient and cheap experimental setups, and straightforward genetic approaches.

Our technology can be used to test in the yeast model if a compound (or already approved drug) increases the lifespan of a single cell compared to the untreated control. This approach could be used for drugs, as well as for lead structures, natural products, supplements of cosmetics, food extracts, or even toxins (like pesticides). The process can be multiplexed, running hundreds of assays on thousands of cells treated with entire compound libraries in parallel.

Apart from the general screening for the effect a drug (or more general, a compound) has on lifespan, the HAPPY-chip could be used to compare the effect of compounds on yeast cells that represent a specific genetic disorder. As the methods to manipulate the genome of a yeast cell are readily available, it is fairly easy to generate yeast models that resemble specific forms of neurodegenerative diseases, cancer, or other unhealthy conditions. Performing drug screening on these cells will highlight compounds of specific interest in defined areas.