PROJECT SUMMARY/ABSTRACT There is an urgent need for nonhuman primate models of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders to help with development of therapies designed to advance brain health. Among NHPs, the common marmoset [Callithrix jacchus (cj)] affords a highly tractable option because of its small size, short lifespan, production of multiple offspring/year and accurate recapitulation of human neuroanatomy. However, the ultimate utility of the marmoset model remains in its infancy due to the paucity of efficient tools to facilitate studies requiring genetic modification, especially those needed to recapitulate complex aspects of brain health. To address this urgent need, the parent project proposed an innovative, more efficient approach to achieve gene editing and transgenesis in marmosets based on the novel use of highly manipulable induced pluripotent stem cells (iPSCs) that can be differentiated to form male germ cells that can ultimately be used to produce transgenic offspring carrying precisely edited alleles of genes relevant to brain health and disease. In Aim 2 of the parent grant, we are optimizing derivation and transplantation of male cjiPSC-derived germ cells into recipient testes and grafts to foster development of transgenic sperm. Here, we are proposing supplemental support for a promising undergraduate candidate to be involved with experiments in this Aim 2 to expose her to this cutting-edge research in marmosets using spatial transcriptomics, stimulate her continued interest in pursuit of a research career and provide her with new skills that will benefit her prospects as a career researcher.

PROJECT NARRATIVE The overarching goals of this project are to develop a marmoset model system to represent the neurobiology of the human brain and to develop a novel pluripotent stem cell/male germline-mediated transgenesis approach to advance the utility of the marmoset model to benefit the brain health research community. This supplement will introduce a promising undergraduate student from an underrepresented groups and disadvantaged background to this cutting-edge research in marmosets using bioinformatics to stimulate her continued interest in pursuit of research careers and provide her with key skills to make her a competitive applicant for MD-PhD programs.