Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model.

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (Treg) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4+CD25+FoxP3+ Tregs from donors improves litter sizes in DEREG mice with depleted Tregs. Our hypothesis is that DEREG mice treated with a single dose of DT will deplete Tregs and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase Tregs and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of Tregs resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of Tregs at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low Treg.

"On the job" learning: A bioinformatics course incorporating undergraduates in actual research projects and manuscript submissions.

The sequencing of whole genomes and the analysis of genetic information continues to fundamentally change biological and medical research. Unfortunately, the people best suited to interpret this data (biologically trained researchers) are commonly discouraged by their own perceived computational limitations. To address this, we developed a course to help alleviate this constraint. Remarkably, in addition to equipping our undergraduates with an informatic toolset, we found our course design helped prepare our students for collaborative research careers in unexpected ways. Instead of simply offering a traditional lecture- or laboratory-based course, we chose a guided inquiry method, where an instructor-selected research question is examined by students in a collaborative analysis with students contributing to experimental design, data collection, and manuscript reporting. While students learn the skills needed to conduct bioinformatic research throughout all sections of the course, importantly, students also gain experience in working as a team and develop important communication skills through working with their partner and the class as a whole, and by contributing to an original research article. Remarkably, in its first three semesters, this novel computational genetics course has generated 45 undergraduate authorships across three peer-reviewed articles. More importantly, the students that took this course acquired a positive research experience, newfound informatics technical proficiency, unprecedented familiarity with manuscript preparation, and an earned sense of achievement. Although this course deals with analyses of genetic systems, we suggest the basic concept of integrating actual research projects into a 16-week undergraduate course could be applied to numerous other research-active academic fields.