PHASE I – WORK PLAN
Embryogenesis
Projects in Embryogenesis and Germline Rejuvenation
Dynamics, Mechanisms and Applications of Embryonic Rejuvenation
Embryonic rejuvenation represents a natural, profound reset of biological age that occurs during early development, specifically around the gastrulation stage. This rejuvenation process is marked by extensive epigenetic, metabolic, and bioelectric changes that collectively reduce biological age to its lowest point, termed “ground zero.” This project aims to explore the mechanisms underlying this event, using state-of-the-art multi-omic profiling, bioelectric pattern analysis in diverse models, including mouse embryos, induced pluripotent stem cells (iPSCs), and embryoids. This will produce a dataset that will be a valuable resource in the exploration of “ground zero” and the rejuvenation events associated with it. By understanding how embryos reset biological age, we hope to apply these insights to novel therapeutic strategies for rejuvenating aging somatic cells and reversing age-related decline. The project will focus on three main objectives: (1) mapping embryonic rejuvenation at high resolution across various models, (2) identifying key genetic and environmental factors that regulate rejuvenation, and (3) developing bioelectric reprogramming techniques to induce rejuvenation without loss of cell identity. This research aims to uncover fundamental biological processes and lay the groundwork for future therapies targeting aging and age-related diseases.
Maintenance of Reduced Biological Age in the Germline
The proposed research investigates the mechanisms of germline maintenance, specifically focusing on the reduced biological age of germ cells and their ability to perpetuate indefinitely across generations. Germ cells maintain a low biological age despite the aging of the parent organism, which is a crucial feature for the preservation of genomic integrity. This project will perform multi-omic profiling to map biological age across different stages of germ cell differentiation and compare it with non-germline cell types in the reproductive organs. Through bulk and single-cell analyses of germ cells from male and female mice, we aim to elucidate how biological age is maintained or reset during gametogenesis. In parallel, we will identify mechanisms that contribute to the indefinite genome maintenance of the germline, with a focus on DNA repair pathways and the role of transposon activity.