PI/PD: Ann Jerse, Ph.D.
Uniformed Services University
The broad objectives of the Administrative Core (Core A) of the Atlantic Coast (AC) STI CRC are to provide the infrastructure needed to help the Center meet its long-term goal of increased understanding and improved control measures for chlamydia and gonorrhea infections. The activities of Core A are organized around the following five specific aims and a management plan has been developed to address each aim. Aim 1 is to foster interactive and synergistic interactions between Center PIs, co-PIs and Core Leaders to maximize research accomplishments and increase the types of significant breakthroughs that occur when experts in different fields work together. Mechanisms to accomplish this goal include monthly teleconferences for Center investigators and annual AC STI CRC meetings where Center PIs, coPIs and Core Leaders present their progress. An outside scientific advisory board (SAB) composed of researchers with diverse experience in STIs will attend two of the AC STI CRC meetings and provide critiques on the progress of individual Research Projects, the Research Cores, and the overall Center. Aim 2 is to provide funds, mentorship, and networking opportunities to talented new investigators working in STI research through the Developmental Research Project (DRP) program. Core A will solicit calls for applications and organize the review panel and review process by which awardees will be selected. Core A will also play a role in developing a training plan for the awardee and will provide DRP awardees with the opportunity to attend and present at an annual NIAID programmatic STI CRC meeting. Aim 3 is to actively facilitate good communications between the Henry Jackson Foundation, who will administer the awards and subawards of the Center, and administrative personnel at the different institutions within the Center. Core A will provide administrative oversight with respect to maintaining all assurances for animal and human use. Aim 4 is to regularly communicate with NIH/NIAID program staff so that our progress is transparent and we are aware of changes in programmatic focus. To promote these interactions, NIAID program staff will be invited to the annual internal AC STI CRC meetings. Aim 5 is to broaden networks within the STI research community by actively seeking and identifying potential collaborations between Center researchers and investigators at other Centers. Besides helping to identify such collaborations, Core A will consult with NIAID program staff for information on expertises or technologies held by other Centers that might help PIs within our center.
PI/PD: Ann Jerse, Ph.D.
Uniformed Services University
The overall goal of the Mouse Infection Core (Core B) is to conduct animal infection experiments for other researchers in the Atlantic Coast STI CRC using mouse models of
Neisseria gonorrhoeae (Ng) and Ng/Chlamydia muridarum (Cm) coinfection developed by our laboratory. Core B is a key integrative component for reaching the Center’s long-term goals and thus, this core is critical to the success of the Center. Core B will provide services for the two research projects in our group (Project 1, Duncan and Project 2, Nicholas/Shafer) and to other Center investigators who need our expertise. Having a Research Core for this purpose is highly beneficial to the Center in that it allows experiments to be conducted in the same manner between labs, and thus standardizes results. It also allows research to proceed in an efficient and cost-effective manner. The coinfection model, which was only recently developed, is technically complicated and it is important that our Center has a mechanism for coordinating its use since understanding STI coinfections is one of the main objectives of our Center. We therefore train individuals in these laboratories as needed. To accomplish the goals of Core B, we have organized our services under the following specific aims: Aim 1) Microbial fitness studies: We conduct competitive infections to measure the relative fitness of mutant and wild-type Ng strains in the lower genital tract of female mice; Aim 2) Pathogenesis studies: We conduct noncompetitive infections to study whether certain Ng factors are required for infection and the impact of these factors on the mouse response to Ng; Aim 3) Coinfection studies: We test Ng mutants in mice that have a Cm infection to determine whether the in vivo phenotypes of the mutants, disease progression, and host responses are altered in the context of coinfection; Aim 4): Product development: We perform immunization and challenge studies with candidate Ng vaccines in the Ng and Ng/Cm infecton models. Should progress by any of Center PIs lead to potential therapeutic treatments (e.g. novel antimicrobials, immunotherapies), we can also test the in vivo efficacy of these candidate products in either model using well-established protocols; Aim 5): Consultation and training: We provide technical advice, assist with experimental designs, and perform hands-on training with other Center PIs and technical staff as needed.
PI/PD: Greg Sempowski, Ph.D.
The overall objective of the Host Response Monitoring Core is to provide centralized, comprehensive and consistent immune monitoring to enhance the activities of the Atlantic Coast Sexually Transmitted Infection Cooperative Research Center investigators. The shared scientific/resource core will provide expertise in systemic and mucosal immunity with an emphasis on humoral, cellular and biomarker analysis. To accomplish Core goals the efforts and expertise of Dr. Sempowski’s cellular immunology lab and Dr. Staats’ mucosal immunology lab have been united. Centralized immune monitoring assays have been divided into three specific aims. 1) Humoral Responses: Provide antibody quantity and isotype assessment by ELISA, and antibody quality (avidity) by surface plasmon resonance. 2) Cellular Responses: Provide mucosal tissue procurement, cellular subset isolation, polychromatic flow cytometry/cell sorting, and functional in vitro restimulation assays for comprehensive host response monitoring to both challenge pathogens and experimental vaccines/adjuvants. Supporting technologies include analysis of the frequency of cytokine producing cells by intracellular staining and flow cytometry, and ELISpot. 3) Multiplex Biomarker Analysis: Provide targeted multiplex protein array profiling of biological samples, such as culture supernatant, serum/plasma, urine or inflammatory exudate, using the luminex bead array platform (Mouse and Human). This technology has the capability of simultaneously quantifying up to 50 distinct analytes (e.g. cytokines, chemokines, hormones, signaling transduction proteins) in a single 50 uL sample. This core will be utilized by all AC-STI-CRC research projects and is critical to the success of the center.