Designing a Genetic Screen to Identify Factors Required for Meiotic Nuclear Rejuvenation

During the natural cycle of life, most eukaryotic organisms grow old, age, and die. A common natural mechanism by which organisms “reset” their lifespan is through sexual reproduction; however, how this rejuvenation takes place remains unknown. My lab has found that meiosis in budding yeast, the developmental program that forms sex cells, eliminates age-induced damage. This involves the formation of a novel nuclear compartment, the Gametogenesis Uninherited Nuclear Compartment (GUNC), which acts as a trash can for accumulated age-induced damage. To understand the molecular details of this process, I worked on designing a screen for genes involved in GUNC formation. My mentor and I fused three different proteins targeted to the GUNC and a protein that is able to bind to a drug-resistance plasmid, in order to couple the inheritance of a selectable DNA marker with the elimination of age-induced damage. Initial testing of these three fusion proteins suggested that they were unable to successfully target the plasmid to the GUNC; as such, testing of additional candidate proteins is necessary. We plan to eventually use this system to identify mutations that disrupt GUNC formation and cause inheritance of the drug-resistance plasmid. By identifying and perturbing proteins involved in GUNC formation, we are hoping to be able to drive the inheritance of specific types of age-induced damage, allowing for the determination of what a symptom versus a cause of aging is.