The Microbes in Health and Disease Training Program is a renewal of the NIH-funded T32 training program previously titled "Microbial Pathogenesis and Host Responses Training Program". As part of the renewal, the program's scientific emphasis has expanded to include both the beneficial and harmful role of microbes; hence, the change of name. This change reflects new insights in microbiology regarding the host microbiome that are underscored in the NIH Roadmap, and new faculty recruited to our campus who are leaders in research on the beneficial role of microbes. These faculty members join existing trainers on this grant to provide our program with this fresh scientific dimension. In addition to the expanded scientific emphasis, the types of students trained in this program has also grown to include postdoctoral trainees (MD, PhD or MD/PhD). This change capitalizes on new campus resources that expand the opportunities for training. A new Microbial Sciences Building (MSB) offers a space that knits together campus microbial sciences with clinical infectious diseases and offers a cohesive training environment for both predoctoral and postdoctoral trainees, including physician-scientists.
The MSB houses the departments of Medical Microbiology & Immunology and Bacteriology, as well as the Food Research Institute (FRI) and the Great Lakes Bioenergy Research Center (GLBRC). The MSB also houses physician-scientists; they have their tenure home in a clinical department, but also hold a joint appointment in a basic science department, and interact and collaborate closely with MSB basic scientists in projects that offer physicians and other trainees the chance for bench-to-bedside translational research. In addition to the MSB, a new Center for Infectious Disease (WisCID) will be established by the UW School of Medicine and Public Health (SMPH), and will be located in the MSB. A central goal of the new Center is to foster inter- and cross-disciplinary research and training for both predoctoral and postdoctoral scientists. The founding of this center illustrates the School's and campus commitment to nurturing cross-disciplinary research and training in microbiology and infectious disease.
The Role of Microbes in Health and Disease.
Humans have evolved to live with microbes: to defend against those that harm us, and maintain those that are beneficial. Microbes too have evolved diverse metabolic activities that allow them to thrive in a wide variety of habitats and in association with all living creatures. The result of this coordinated evolution is a spectacular diversity of interactions between microbes and the world, and a diversity of ways in which microbes affect our lives. Our expanded program is designed to train students and postdoctoral fellows in the use of cutting-edge tools to investigate the microbe-animal interface and microbe contributions to human health and disease.
Infectious diseases are a leading cause of human mortality worldwide and a major cause of death in the United States. Their significance is increasing due to:
- The emergence of newly identified pathogens and reemergence of known pathogens.
- The increasing population of immune-compromised patients with to HIV /AIDS, organ transplantation, cancer and cancer therapy, hospitalization and intensive care, and aging.
- Microbial development of antibiotic resistance.
- The risks that are related to mass processing and distribution of foods
- New infectious or immunological etiologies for cardiovascular, neurological, and gastrointestinal diseases and cancer.
- Demonstrated or potential bioterrorism and biowarfare.
In view of the public health significance of infectious disease, there is a significant societal need for the training of a new generation of pre- and post-doctoral scientists in basic mechanisms of microbial pathogenesis and host response. UW-Madison has great investigator expertise and depth in these areas. The 28 faculty trainers on this proposal include faculty with long-standing research and NIH or equivalent funding for programs in microbiology and infectious diseases.
The role of microbes in disease is well known, but recently has there been increasing awareness that beneficial or neutral microbes can profoundly affect health through their influence on host development, nutrition, and immunity. To understand how microbes cause disease, scientists now recognize that we must elucidate how long-term benign or beneficial interactions between microbes and hosts are maintained, and how they affect host immunity and development. For example, the intestinal flora can regulate immunity in the lung and dictate an asthmatic response to mold. Similarly, Dr. Jo Handelsman (a program trainer) has found that a systemic pathogen’s toxicity can be controlled by the intestinal flora. Thus, to prevent or treat disease, we need to study a microbial pathogen in the context of its microbial community, rather than in isolation.
UW-Madison has recently invested in a series of "cluster hires": faculty whose expertise complements and expands on the campus's strengths. One of these cluster hires was in the area of symbiosis, emphasizing the beneficial contributions of microbes to host health. The synergy of research of faculty in the Symbiosis cluster and the Microbial Pathogenesis and Host Response community has spurred our vision of this training grant as "Microbes in Health and Disease" in which we will train researchers to investigate the mechanisms of the microbial-host interface, and use the knowledge gained to combat disease and promote health. Our vision is timely given the newly announced NIH Roadmap Human Microbiome Project "to characterize the microbial content of sites in the human body" and analyze "its role in human health and disease". The complexity of the human microbiome is dramatic: the intestine alone is thought to harbor over 1000 species of bacteria. Moreover, studies of model systems have revealed that animal intestinal microbes contribute to host development, nutrition and obesity, physiology, morphology and immunity. The mechanisms underlying these effects remain obscure and are the subject of research of several trainers. For example, Drs. McFall-Ngai, Ruby, and Goodrich-Blair examine the molecular, cellular, and physiological aspects of binary beneficial invertebrate animal-microbe interactions, while Dr. Currie studies the chemical and physiological relationships between fungal farming ants and their bacterial and fungal symbionts.
Expansion of Program to Include Pre- and Post-doctoral Trainees
UW-Madison attracts a large and talented pool of pre- and post-doctoral trainee candidates, including members of underrepresented minorities. We emphasize that the highly regarded MDTP, which serves as the main source for pre-doctoral trainees, is one of the most successful graduate programs at the UW-Madison, and nationally, in recruiting and enrolling underrepresented minority students. Since its inception in 1998, the MDTP has admitted 35 underrepresented minority students, more than 19% of all admissions, a proportion far higher than that of UW’s proportion of underrepresented minority students.
We seek to build on this record of training success. Opportunities for cutting-edge training in this discipline abound on our campus. Three new developments will synergize to offer outstanding post-doctoral education and training at UW-Madison:
- The Microbial Sciences Building (MSB) brings basic and clinical microbiology together into one exciting space.
The MSB is the physical hub of the Training Program and promotes increased interactions among physicians and scientists. There is a long-standing tradition of close collaboration among the clinical and basic scientists in microbiology and infectious disease across the UW-Madison campus. Faculty from the department of MMI and the clinical sections of Infectious Disease from the departments of Medicine and Pediatrics already team-teach a full-year course in the second year of medical school. The course, Infection and Immunity (I&I) is among the most popular and favorably reviewed courses in the medical school’s curriculum. This collaborative effort is also evident in research and training interactions of the physician-scientist faculty (Andes, Gern, Kenney Huttenlocher, Klein and Striker) with members of MMI and Bacteriology. Each of the MD trainers participates in the MDTP program, and they sit on numerous thesis committees with other trainers, hold federal grants together, and publish together. These interactions have increased in the MSB, where 4 of these physician scientists have their laboratory space. The physical proximity of physician and basic scientists will expose MD postdoctoral trainees to basic research labs and training in MSB, and conversely, PhD pre- and post-doctoral trainees to the labs and translational research opportunities in physician scientist labs. The constant interplay among these disciplines will positively shape the scientific questions that trainees tackle in the lab and translate from the bench. Dr Huttenlocher, a physician scientist, is a co-director of the Medical Scientist Training Program (MSTP). She can thus link these outstanding pre-doctoral MD/PhD students with suitable labs, and herself serve as a physician-scientist role model engaging in translational research.
- The WI Center for Infectious Disease (WisCID) will highlight the discipline and provide programmatic resources for research and training.
The Center for Infectious Disease (WisCID) will promote interdisciplinary interactions in the MSB. WisCID will bring a sharp, effective focus to the study of microbiology, symbiosis and infectious diseases at our medical school and campus. It will integrate currently fragmented effort of physicians and scientists into a synergistic matrix and allow them to better apply the tools of microbiology, immunology and public health to promote health and combat infectious diseases. It will facilitate, with a newly supported core, translational research opportunities for basic scientists (important today for the NIH roadmap) and provide physician investigators exposure to the rigorous scientific methods that are now available and essential to tackle key clinical and public health problems. Dr. Klein, the PI of this T32 training grant, will be the Center’s director and Dr. Welch (MMI Chair, and trainer), the associate director. Two interdisciplinary research projects are already underway under its aegis: Klein is PI on an antimicrobial drug discovery project in conjunction with 5 other physician and basic scientist trainers on this proposal. Dr. Huttenlocher is PI on a anti-inflammatory drug discovery project. Center educational activities will include a featured seminar series on Microbiology and Infectious Disease to be held in the MSB’s 450-seat auditorium. Several symposia on cutting edge topics, including "Immunity/Inflammation", and "Beneficial Role of Microbes in Health" are planned. These activities will expose pre- and post-doctoral trainees to leading-edge topics in the field in an environment where experts from multiple disciplines – basic, clinical and public health – lecture, debate, interact and collaborate.
- The School of Medicine and Public Health has redoubled its efforts in the area of clinical and translational research by recently securing an NIH-supported Clinical and Translational Science Awards and establishing the Institute for Clinical and Translational Research (ICTR), which will provide complimentary opportunities for advanced training in infectious disease translational research.
The ICTR will offer infectious disease translational research training opportunities. In recent years, MD fellows in the section of Infectious Disease in Internal Medicine have taken advantage of coursework and instruction for training in clinical and translational research through an NIH-funded (K30) Clinical Investigator Preparatory Program (CIPP). Dr. Chris Crnich received this training and also matriculated for a PhD in public health. Dr. Nassia Safdar similarly received this training and obtained an MPH during fellowship. Both are now junior faculty engaged in clinical/translational research.
Our training program was founded within the context of a strong institutional commitment to translational research, particularly with the recent establishment of ICTR. The goal of the institute is to transform health research so that discoveries flow from basic and clinical investigation into translation and practice. ICTR will consist of cores that provide support and service to researchers and trainees: Education, Biostatistics/Medical Bioinformatics, and Clinical and Population-based Research. ICTR will:
- Aid trainees with grants and budgets.
- Ensure compliance and subject safety in on-going research studies.
- Offer standardized training to research nurses and coordinators.
- Help streamline the movement of clinical trial protocols through the Institutional Review Board.
Our trainees who elect translational research will be able to capitalize on a strong institutional infrastructure to assist with clinical and translational research training and implementation. Importantly, our trainees will also be able to matriculate for a MS or PhD degree in clinical/translational investigation.
