Design of a Lyme Disease Vaccine as an Active Learning Approach in a Novel Interdisciplinary Graduate-Level Course.

A biomedical sciences graduate program needed an introductory class that would develop skills for students interested in a wide variety of disciplines, such as microbiology or cancer biology, and a diverse array of biomedical careers. Faculty created a year-long student-centered course, Scientific Discovery, to serve this need. The course was divided into four modules with progressive skill outcomes. Each module had a focus related to each of the major research areas of the collective faculty: molecular biology, biochemistry, neuroscience, and infectious disease. First-year graduate students enter the program with relevant college-level biology and chemistry coursework but not in-depth content knowledge of any of the focus areas. Each module features a biomedical problem for the students to gain specific content knowledge while developing skills outcomes, such as the ability to conduct scholarly inquiry. In 2015, the theme of the infectious disease module was to create an effective human vaccine to prevent Lyme disease. The module required students to learn fundamental concepts of microbiology and immunology and then apply that knowledge to design their own Lyme disease vaccine. The class culminated with students communicating their creative designs in the form of a "white paper" and a pitch to "potential investors." By the end of the module, students had developed fundamental knowledge, applied that knowledge with great creativity, and met the skills learning outcomes, as evidenced by their ability to conduct scholarly inquiry and apply knowledge gained during this module to a novel problem, as part of their final exam.

The N terminus of type III secretion needle protein YscF from Yersinia pestis functions to modulate innate immune responses.

The type III secretion system is employed by many pathogens, including the genera Yersinia, Shigella, Pseudomonas, and Salmonella, to deliver effector proteins into eukaryotic cells. The injectisome needle is formed by the polymerization of a single protein, e.g., YscF (Yersinia pestis), PscF (Pseudomonas aeruginosa), PrgI (Salmonella enterica SPI-1), SsaG (Salmonella enterica SPI-2), or MxiH (Shigella flexneri). In this study, we demonstrated that the N termini of some needle proteins, particularly the N terminus of YscF from Yersinia pestis, influences host immune responses. The N termini of several needle proteins were truncated and tested for the ability to induce inflammatory responses in a human monocytic cell line (THP-1 cells). Truncated needle proteins induced proinflammatory cytokines to different magnitudes than the corresponding wild-type proteins, except SsaG. Notably, N-terminally truncated YscF induced significantly higher activation of NF-κB and/or AP-1 and higher induction of proinflammatory cytokines, suggesting that a function of the N terminus of YscF is interference with host sensing of YscF, consistent with Y. pestis pathogenesis. To directly test the ability of the N terminus of YscF to suppress cytokine induction, a YscF-SsaG chimera with 15 N-terminal amino acids from YscF added to SsaG was constructed. The chimeric YscF-SsaG induced lower levels of cytokines than wild-type SsaG. However, the addition of 15 random amino acids to SsaG had no effect on NF-κB/AP-1 activation. These results suggest that the N terminus of YscF can function to decrease cytokine induction, perhaps contributing to a favorable immune environment leading to survival of Y. pestis within the eukaryotic host.