Project Summary This is a Diversity Supplement to support the development of the career of Yoko Takashima, a second year PhD student who is engaged in work related to R01 HD059060, “Regulation of Gamete Use and Neural Pathways in Reproduction”. Her work focuses on three primary aims related to the determinants of reproductive success. The first aim is to elucidate the functional consequences of the transfer of exosomes (vesicles) from males to females during mating, a phenomenon seen in mammals and in Drosophila. The function of these transferred exosomes, minute lipid-bound vesicles that encapsulate and transfer proteins and RNAs, is not well- understood in any system. In Drosophila they have been suggested to affect the process of sperm competition, in which ejaculates from successive males compete for fertilization opportunities. Ms. Takashima will assess the variation in exosome production, transfer, and its effects on sperm competition, allowing her to apply genome-wide association (GWAS) approaches to identify previously unknown genetic variants that impact exosome biology. In her second aim, Ms. Takashima will dissect the mechanism(s) employed by exosome contents to impact female post-mating responses, including a specific assay of sperm competitive ability. Finally, in Aim 3, these data will be incorporated into a promising statistical modeling approach, the Bradley-Terry model, to quantify the effects of perturbed seminal exosomes on male competitive-reproductive success. We have devised a detailed mentoring plan that will provide Ms. Takashima tailored support for both her scientific development and to guide her in achieving her career goals. She will receive academic and research training, training in presentational skills and responsible conduct in research, teaching/mentoring experience, and guidance to complete an impactful PhD. She will also receive additional guidance to help her choose among career options that she is considering; this will involve one-on-one guidance from her mentors, networking that we will set up for her with colleagues and alumni in careers she is exploring, as well as workshops and resources at Cornell and at conferences she will attend.

Project Narrative This Diversity Supplement is for the training of Yoko Takashima, a second-year Latina graduate student who recently joined our labs. Yoko will be trained in research by investigating at the bench and statistically an important reproductive interaction between females and males: specifically, how male seminal exosomes regulate the paternity of a female’s progeny; she will learn and use multiple areas new to her including statistical analysis, GWAS and functional genetic analysis, reproductive phenotypes, and quantitative immunofluorescence microscopy. Yoko will be mentored in her science and towards her career objectives through intensive one- on-one discussions with her mentors and with colleagues and alumni in career areas of interest, discussions with her mentors and labs about research results, planning, and ethics as well as through coursework, workshops, science-presentation, meeting attendance, and student- mentoring.