Systems Biology Approaches to Single-Cell Aging by using Novel Microfluidic Platforms

2013 new Scholar Award in aging

Cellular aging is the dynamic process of accumulating genetic and molecular changes in cells. A variety of diseases, such as cancer, type-2 diabetes, and Alzheimer's disease, are linked to aging. Of the approximately 150,000 people who die everyday in the world, two thirds die of age-related causes. Despite the pressing need to alleviate this problem, our understanding into the mechanisms of cellular aging and how these mechanisms are coupled to the initiation of various disease states is very limited. For example, we know very little about the chromosome instabilities occurring in old cells. A basic understanding on the set of genes and gene networks responsible from directly regulating lifespan and the mechanisms used in this regulation is also missing. This lack of understanding is contributed by the fact that cellular aging is a complex phenotype to measure and comprehensive studies on aging require the application of novel experimental approaches and technological platforms. Using the replicative aging of the yeast Saccharomyces cerevisiae as an aging model, we will apply quantitative systems biology approaches to investigate: 1. the age-associated genome instability events in single-cells; and 2. the dynamics of stress response in individual yeast cells during aging. To facilitate these approaches, novel microfluidic platforms automating the separation of daughter cells away from their mothers will be used. Aging mother cells will be time-dynamically imaged with high efficiency and throughput until they no longer produce daughter cells. Results from these studies will broaden our limited understanding on how single-cells age by elucidating which genetic and phenotypic changes accompany the aging process.

Murat Acar Ph.D.
Yale University