Medical Microbiology & Immunology - Department of Medical ...

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In Madison, Don continued to study mycobacterial cell wall lipids with major ... research on the major public health issue of vaccine induced immunity in. TB.

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November 31, 2012 Volume 4, Issue 1 Department Faculty: David Andes, MD James Bangs, PhD Curtis Brandt, PhD Joseph Dillard, PhD Jenny Gumperz, PhD Christina Hull, PhD Anna Huttenlocher, MD Nancy Keller, PhD Bruce Klein, MD Laura Knoll, PhD Miroslav Malkovsky, MD, PhD John Mansfield, PhD Margaret McFall-Ngai, PhD Andrew Mehle, PhD Donna Paulnock, PhD Caitlin Pepperell, MD Edward Ruby, PhD JD Sauer, PhD Ronald Schell, PhD Robert Striker, MD, PhD Rodney Welch, PhD, Dept. Chair Jon Woods, MD, PhD Emeritus Instructors: Julie Franz, MS Judith Manning, PhD Janet Schrader, PhD Joanne Weber, BS, MT Emeritus Faculty: Harry Hinze, PhD Richard Proctor, MD William Weidanz, PhD Dept Administrator: Tracy Wiklund Newsletter Editor: Alicia Hamilton Tracy Wiklund

Medical Microbiology & Immunology   Greetings!

Greetings again to all of our MMI alumni and friends! It has been a relatively mild and warm Fall thus far in Madison. I am hoping the mild weather will continue through the winter. I am not a big fan of the snow and cold. Historically, our Department faculty members have not taken sabbaticals. However, that situation is changing for us. Drs. Margaret McFall-Ngai and Ned Ruby just returned from spending the past academic year at Cal Tech. They said it was a very stimulating year, and they have returned with some new great ideas for their teaching and research programs. Dr. Bruce Klein is planning to take a sabbatical in Aberdeen, Scotland during the coming calendar year. Yours truly is also planning to take a six month sabbatical in 2013 - I will split my time working in my lab and in England. While I am gone, Dr. Ned Ruby has agreed to serve as Acting Chair of MMI. In terms of faculty awards and recognition, we have had a great stretch of good fortune. First, one of our junior faculty members, Dr. Andy Mehle, was named a Shaw Scholar; he will receive a considerable award of flexible research funds from the Shaw family endowment in Milwaukee, WI. Dr. Ned Ruby was just named the Steenbock Professor of Microbiological Science. This endowed Professorship is given via a campus-wide competition, and provides flexible research funds for Dr. Ruby’s laboratory for ten years. This year, Dr. Margaret McFall-Ngai was named a Fellow of the American Academy of Arts and Sciences. At her induction ceremony in October, she was one of the five invited speakers among

the new inductees. Some of her fellow inductees this year included the actor Daniel Day-Lewis, journalist Judy Woodruff, composer Andre Previn, playright Neil Simon and Griffin P. Rodgers, director of the National Institute of Diabetes and Digestive and Kidney Diseases. In the last newsletter, I mentioned we have experienced significant turnover of our staff, particularly with our undergraduate instructors. Because of this, we have been shifting around teaching assignments. This fall I have taken over the pathogenic bacteriology laboratory formerly taught by Joanne Weber. This is the first time in over 20 years that I have been teaching in a laboratory setting and I have to say, I am truly enjoying the experience. There are 55 students split between two sections. The course requires a lot of logistical attention and it gets quite hectic at times, but I have found the direct contact with our undergraduates to be very rewarding. By midsemester, I had learned nearly every student’s name and in many cases gotten a significant impression of their intellects and personalities. I have found them to be bright, energetic, focused and a lot of fun. ~ Rod Welch, Department Chair

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Back to Seasons: Welcoming Caitlin Pepperell After living in the Mediterranean climate of the San Francisco bay area for eight years, I am back to four proper, distinct seasons here in Madison. I have lived in some seriously cold places (Ottawa, Montreal) and people tell me that Madison can be comparable, but last winter was a pretty gentle reintroduction to snow and ice. My research is adapting to this new environment as well. I have made connections with an outstanding group of ecologists, statisticians and computer scientists here on campus. Happily for me, population genetics has been in a growth spurt at UW-Madison over the past few years. We had the first of what I hope will be many joint UW population genetics lab meetings this summer. So far, two things have surprised me about Madison and Wisconsin. I did not know that Madison has such beautiful architecture, and when my husband and I were looking for a place to buy, the options would include gorgeous Victorians and original, prairie style homes. In the end, we settled on an 86-year old house, and now we are learning how to fix beautiful old homes. The other thing that has surprised me is the diversity of locally endemic human pathogens. Apparently Wisconsin’s fertile soil and abundant waterways support

a great variety of disease vectors and free-living pathogens. A member of the UW hospital infectious diseases team told me she takes prophylactic doxycycline whenever she goes camping here. I don’t think I’ll do that, but it seems to me there are lots of local opportunities to learn about why some organisms “choose” (in the evolutionary sense) to become pathogens. I am really looking forward to delving into these questions over the next few years as I build my lab and get to know the Madison microbial sciences community. ~ Caitlin Pepperell, Assistant Professor

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Notes from the Andes Lab As you may already know, in the Andes lab we work with Candida albicans. This organism’s most impressive virulence attribute is the ability to propagate as a biofilm attached to a medical device, such as a venous catheter. This critical factor alone is responsible for the majority of invasive and persistent disease. As conventional antimicrobials are ineffective for treatment of these lifethreatening infections, further understanding of the biofilm lifestyle and how the cells survive drug therapy is desperately needed. The microbe-derived extracellular matrix, a distinguishing feature of biofilms, has been linked to several roles in biofilm pathogenesis. Over the last few years we have concentrated our efforts defining the key genes responsible for production of the extracellular biofilm matrix components and analyzing their role in biofilm pathogenesis. The current investigation capitalizes on our progress during the last few years. We have identified the role of one matrix component, β-1,3 glucan, for biofilm resistance and dispersion. Our excitement for future investigation is based upon two unexpected observations: First, the surprising identification of two additional abundant matrix polysaccharides, β1,6 glucan and αmannan. Second, we have

demonstrated an interaction among these matrix components. Our major objectives now are to define the genetic pathways governing production, delivery, and maturation of the entire complement of polysaccharides in matrix and to discern the function of these matrix components alone and in a coordinated fashion in biofilm pathogenesis. To accomplish this, Dr. Andes has put together an excellent team of scientists and dedicated students. We have six full time "bench scientists" (Alex Lepak, Karen Marchillo, Jeniel Nett, Jamie Van Hecker, Robert Zarsnowski and myself), one post-doc (Jonathan Cabezas), three graduate students (Jessica Edward, Kaitlin Mitchell and Heather Taff), and three undergrads (Emily Reinicke, Kasey Reeves and Elliot Thieleke). We are a very diverse and interesting group of people who love science, food, music and life in general. ~ Hiram Sanchez, Lab manager

From Left to Right Hiram Sanchez, Jamie Van Hecker, David Andes, Karen Marcillo, Mike Cain, Anna Moreland, Heather Taff and Alex Lepak (some other lab members couldn't make it to the Memorial Union that day).

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On the Death of Professor Emeritus Donald Ward Smith Donald Ward Smith, Emeritus Professor of Medical Microbiology & Immunology, passed away in Madison, Wisconsin, on Saturday, September 29th, 2012, at the age of 86. He was born in Flint, Michigan in 1926. He served in the US Navy and attended the Michigan College of Mining and Technology with support from the GI Bill. He received a BA degree in Chemistry. Following graduation, he obtained a teaching assistantship in the Bacteriology Department at the University of Michigan in Ann Arbor. He joined the laboratory of Professor Harrison M. Randall, an international authority on the measurement of infrared spectra, who wished to apply infrared spectroscopy to the investigation of tuberculosis (TB). Don conducted studies of the comparative biochemistry of mycobacterial lipids and earned his PhD in medical microbiology in 1951. After two years as a post-doctoral fellow, Don accepted a faculty position in the Department of Medical Microbiology at the University of Wisconsin-Madison, where he rose through the ranks to Professor (1965) and retired in 1991. At the time of his death, he was Professor Emeritus in the Department of Medical Microbiology and Immunology. In Madison, Don continued to study mycobacterial cell wall lipids with major funding from the National Tuberculosis Association. Interactions with Dr. Halfdan Mahler at the World Health Organization lead Don to focus his research on the major public health issue of vaccine induced immunity in TB. In the mid-1960’s Don theorized that the striking differences in the reported efficacy of various experimental TB vaccines was likely due to differences in the animal models used to test the vaccines. He organized a large international collaborative effort involving eight laboratories to evaluate 6 TB vaccines in 21 different animal models. Each laboratory ranked the six vaccines according to efficacy. No two animal models ranked the vaccines in the same order. Don was convinced that, to evaluate potential human vaccines against tuberculosis, a uniform animal model replicating the natural infection in humans would be required. He pioneered a guinea pig model with pulmonary inhalation of small numbers of bacteria using an aerosol exposure chamber constructed in the Engineering Shops at the University of Wisconsin. Using the “Madison Chamber”, Don and his group compared the infection of vaccinated and non-vaccinated guinea pigs. His work highlighted

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  the initial infection and progression to disease, which involved dissemination of bacteria through the blood stream and reseeding of the lung, resulting in so-called secondary lesions. His findings had direct relevance for understanding the failure of BCG vaccine to protect against TB in parts of the world where frequent exposure to low-virulence clinical and/or environmental isolates interferes with vaccination. The NIH funded Don’s research for more than 30 years. His seminal contributions to the understanding of experimental TB in animal models continue to have a major impact on the field. His work continues to be highly cited and the “Madison Chamber” is still widely used in laboratories around the world. He published 90 papers in peer-reviewed journals and presented his work at national and international meetings. He received many honors and awards for his research. He was an active member of ASM and delivered the “Real-time Analysis of Host-Pathogen Interactions” Lecture at the Las Vegas meeting in 1994. Don was a dedicated and outstanding mentor to the many PhD students and post-doctoral fellows he trained during his career. He taught and led by example, conducting research with the highest standards. He valued the input from all the members of his research team. Everyone was included in the planning of experiments and in the discussion of research results. He often said that his success as a scientist was due to the fact that he surrounded himself with people who were smarter than he was (We knew better). Don’s impact extended beyond those in his research group through teaching of Med Micro 740, a course in host-pathogen interactions that was required for graduate students in the Medical Microbiology graduate program. A demanding instructor, Don instilled in students an appreciation for experimental design and critical analysis of data. Don’s approach to science exemplified the famous quote that is inscribed on a plaque on Bascom Hall “We believe that the great state university of Wisconsin should ever encourage that continual and fearless sifting and winnowing by which alone the truth can be found.” Don was truly loved by his students, and he considered his students “family”. He was father, teacher and role model. He supported his students and let them grow. His legacy endures in our teaching, research and clinical efforts, but more importantly in our hearts, and the hearts of the countless students and colleagues, and others whose lives he touched and changed. We will be forever grateful.

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Our Sabbatical Leaves at Caltech Margaret McFall-Ngai and Ned Ruby This was the first time during the course of our careers that either of us had taken a sabbatical. We have moved from one university to another a few times, and that has served to introduce us to new colleagues and ideas, as well as keep us from becoming too settled and comfortable. But these are also good reasons for taking a sabbatical leave. Visiting professorships from the Gordon and Betty Moore Foundation allowed us to stay at Caltech for the entire 2011-2012 academic year. During that period, our sponsor was the geomicrobiologist Diane Newman; with her help we met other Caltech faculty with whom we have begun successful interactions. Margaret’s story. My goal was to develop new collaborations that would facilitate our study of the biophysics underlying microbial cell capture by ciliated host epithelial cells. The

squid-vibrio system with which my lab works offers a rare opportunity to visualize and model, in real time, the steps associated with the engagement of symbiont cells by host tissues. I began a project that involves four other PIs: John Dabiri, Applied Physics, and his student, Jana Nawroth, who generated preliminary data using specially constructed animal flow chambers; Scott Fraser, Biology, who can visualize and quantify the activity of ciliated fields by confocal microscopy; Eva Kanso, Aerospace Engineering, USC, who mathematically modeled bulk and microfluidic flow across host tissues; and, Ned’s lab, who provided bacteriological expertise. Our preliminary studies have led to an NIH proposal that supports this group’s continued collaboration. I also joined Dr. Newman in designing the first-year biology course for Caltech’s non-biology majors (Bi1). Microbes are now recognized to play major roles in such processes as the maintenance of human health and ecosystem sustainability. Concomitant with this

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  growing awareness of the biological centrality of microbes, technological advances have poised biology to unify under a series of basic principles. Our goal was to provide Caltech’s chemistry, engineering and physics students with a robust introductory framework in biology, so that they would be better prepared to collaborate with biologists. Ned’s story: My main research interaction was with Scott Fraser, with whom I wrote a proposal to the Moore Foundation’s Marine Microbial Initiative. The proposed work, which is now funded, is a collaboration between my lab, and four other PIs: Scott will develop the instrumentation, Rob Knight, U Colorado, will perform the bioinformatics; Jenny Reed, U Wisconsin, will construct the necessary bacterial metabolic modeling; and Margaret will provide expertise with the animal model. At the core of the project is the development of technologies for determining the gene expression patterns of populations of bacteria by measuring the transcriptome of individual cells. The patterns from dozens of individuals will be statistically averaged to create a picture of the most robust responses

characterizing this population as it executes ecological transitions from one habitat (seawater) to another (the squid light organ). While there has been great interest in the development and application of single bacterialcell transcriptomics, to date the required technology has not been successfully brought to bear. The instrumentation and approaches derived in our study can be generalized to any bacterial population, and applied to other ecological transitions. Research collaborations initiated with other faculty at Caltech have allowed me to incorporate recent advances in understanding the structure (Prof. Grant Jensen, Biology) and function (Prof. Rob Phillips, Applied Physics) of sheathed bacterial flagella in my teaching in MMI courses. One unexpected thing Margaret and I learned this year was how few of our fellow faculty, both here and at Caltech, take the opportunity to go on a sabbatical, and bring new ideas to their research and teaching missions. We would encourage more of our colleagues to consider the benefits of this experience.

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Life Beyond Microbiology For each newsletter, we try to feature a couple of alumni who are doing interesting work in their fields. In preparing this newsletter, I contacted an alumnus who graduated with a Master’s degree and holds an amazingly interesting job. To my chagrin, she declined. Her rationale for not being featured included: she hasn’t published anything, did not finish a PhD, and does not work in the field of microbiology. She felt that folks reading the newsletter would not be interested in hearing what she has been up to. This took me by surprise and made me think about alumni-department relationships. Very few students who study science actually go on to finish advanced degrees and publish in their fields, yet many of them are very successful in the life and work paths they choose (or fall into!). It is important to remember and honor

individuals who began here, but ended up somewhere totally different. How a person gets from point A to point B is often more interesting and educational than the starting and ending points themselves. Not to mention the fact that, even though many MMI alumni are no longer working in the field of microbiology, they wouldn't be where they are today or have had the opportunities they've had without their Microbiology training. Life is amazing in that way. Most of the 1,000 people who receive our newsletter fall into this category. It is important for you all to know that we, as a department, consider you – all of our alumni - “family”. We are fascinated to know what life adventures you have had (or are having). So, if you ever get bored, we would love to hear about how you ended up doing whatever it is that you’re doing. ~ Alicia Hamilton, Newsletter Editor  

Alumni Update I : Heather Meiselman Heather Meiselman graduated in Spring 2010 after working with Dr. Robert Striker on testing the effect of Vitamin D on the replication of Dengue Virus. She is currently attending Ben-Gurion University (BGU) in Israel, a school that incorporates the traditional medical school curriculum with global heath and medicine classes. BGU's Soroka University Medical Center serves a diverse patient population, including Bedouin and Ethiopian communities and immigrant Jews. In her fourth year, Heather will have the opportunity to attend a clinical clerkship at Columbia University, a center that focuses on global health or in a developing country. When Heather decided to attend medical school in Israel, she was attracted to the idea of studying a

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unique curriculum in an exotic location. So far, school in Israel has been quite the adventure. A year ago, she could not imagine taking weekend trips to Tel Aviv and Jerusalem or spending Succoth vacation in Jordan, hiking around Wadi Rum and visiting Petra. She was unaware of the close relationships she would build with her Israeli second cousins. Their location discovered only from Facebook. Yet, Heather only anticipated half of the challenges of beginning a new life in Israel - setting up a bank account, finding an apartment, signing a contract for a cell phone, and obtaining internet. In addition, learning Hebrew on top of her medical studies has not been the easiest feat. Even more difficult was becoming accustomed to different cultural peculiarities - having class Sunday through Thursday, realizing Israelis do not wait in "lines," and being able to taste just about everything in the supermarket before buying it. But the most difficult cultural difference she has had to overcome is having her backpack checked every time she enters a public building and accepting the presence of a bomb shelter on every floor of a building.

Alumni Update II: Roberta Hiat Wilen, PhD After graduating with a BS in Medical Microbiology, I went to work as a research assistant at NYU Medical Center in New York City. I ran a tissue culture lab, growing fibroblasts for various research products. I enjoyed this very much, but missed my "bugs". While working at the Medical Center I went back to school at night at NYU (paid for by NYU) and got a Master's and Ph.D. in Epidemiology. From there, I became a hospital epidemiologist specializing in infection control. After marrying, we moved to North Carolina where I continued my career as a hospital epidemiologist. Infection control was an emerging field back then, and it was a joyful time. In 1996 I started my own consulting company helping medical and dental facilities with infection control and OSHA training. North Carolina has some of the strictest infection control laws of all the states. Per our state law, any facility that performs invasive procedures must designate

someone to take a certified state class in infection control and have specific infection control policies mandated by the state. One of my proudest accomplishments was putting the original program together and being the first person in North Carolina certified to teach these classes. Life has been good.

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Alumni Update III: Gladys Gonzalez-Aviles I am a Puerto Rico native, and I arrived to UW-Madison in August 2003. It was not an easy transition. The language barrier and graduate school were not easy tasks, and my first semester was very challenging. With a high determination, I conquered those challenges and I obtained an MS from the MMI Program in December of 2006 from Dr. Robert Striker’s laboratory. Very early in my studies I discovered a high affinity to public health related work, and I made it my goal to find a job at the Centers for Disease Control in Atlanta, GA, where I am currently. I have an amazing job. I work at the reference laboratory for the Pertussis (whopping cough) and Diphtheria laboratory, and I am also the Coordinator for the Latin American Pertussis Project (LAPP). Pertussis is the most poorly controlled bacterial vaccine preventable disease in the

Americas. For LAPP I travel to Argentina, Panama and Mexico to do technology transfer for pertussis diagnostics, translate and coordinate trainings/protocols, do mentorship and technical assistance, and develop strong relationships with the ministries of health and stakeholders for each of the countries. This is a very rewarding job, and I have learned so much; not only about diagnostics and epidemiology but also about culture, socioeconomics and politics. I am a true believer that you should dream big. The road to get to that big dream can be bumpy, but that just make the ride so much more interesting. One of my interests is to get involved with recent college graduates for career advice; you can do so much with a degree in microbiology. My long-term career goal is to eventually transfer to CDC-Dengue Branch in Puerto Rico to return not only to my island, but also to my virology roots.

Alumni Update IV: Petra Kohler Life as a scientist after UW-Madison My first stop after graduation was a postdoctoral position in Pat Schlievert’s lab at the University of Minnesota. I was fortunate to have two postdoc advisors and I was co-mentored by Gary Dunny at U of MN. During my time in MMI, I was a student in Joe Dillard’s lab and I focused on molecular genetics and protein characterization. The biggest challenge in moving to my postdoc lab was that my focus shifted to host-pathogen interactions. I went from studying a system for which there is no good animal model to

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understanding host-pathogen relationships in staphylococcal and enterococcal biofilm infections. A primary focus of the Schlievert lab is the study of staphylococcal toxins and I was able to use my training in molecular genetics and protein characterization for projects involving characterization of staphylococcal enterotoxins. After 18 months in my postdoc position, I encountered an opportunity that I did not expect and that I could not refuse. I got a job offer as a senior microbiologist at 3M Company in St. Paul, MN. I have been working for 3M since 2010 in the company’s Corporate Research Laboratory, an organization that employs hundreds of laboratory scientists responsible for research and technology development. My colleagues are materials scientists, chemists, physicists, biologists, and engineers; and I love learning about diverse fields of science every day at my job. I work with my coworkers to develop technologies, mostly in the field of health care. My training at UW prepared me well for my job, especially in the area of science communication. Because my colleagues have diverse backgrounds, communicating my results and ideas clearly is essential to productive collaboration. I am looking forward to the day when my inventions are incorporated into commercialized products that improve the quality of life for patients.

Upcoming Events 2013 Perlman Symposium On Friday, April 12, 2013 Medical Microbiology & Immunology will host its fourth annual Perlman Symposium on Antibiotic Discovery and Development. The symposium will include a morning session of local speakers, an invited keynote speaker, and an early afternoon poster session. More information will be made available after the holidays at:

http://perlman.medmicro.wisc.edu/ MMI to hold Mixer at 2013 American Society for Microbiology Annual Meeting The department of Medical Microbiology & Immunology will host a mixer for past and present associates of the department. For more information on the ASM meeting, please go to: http://gm.asm.org/   More information on the MMI mixer will be made available at:

http://www.medmicro.wisc.edu/index.php  

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