Case Western Reserve University



Message from Jonathan Karn, Ph.D.
Department Chair

Chairman Jonathan KarmThe Department of Molecular Biology and Microbiology provides a focus within the School of Medicine for the study of the growth and development of microorganisms at the molecular level. Many of the research programs in the Department concern fundamental mechanisms using the tools of Molecular Biology: How is gene expression controlled? What is the role of RNA processing and surveillance in gene expression? How do surface molecules regulate molecular signaling events? Other questions under investigation are specific to microorganisms: How do bacteria and viruses survive in their chosen environment? How do they deal with the host's potent immune response? What genes are responsible for their pathogenesis? How is the latency and reactivation of infection achieved? How can we use our results to improve prevention, diagnosis and treatment of infectious diseases?

We study microbial systems both for the insights that they bring to the study of molecular and cellular biology and to improve our understanding of infectious diseases. Viruses provide exquisitely adapted probes of the host cell's normal functions. Historically, studies of viruses have provided numerous insights into the control of gene expression at the transcriptional, post-transcriptional, and translational levels. Fundamental processes such as repression of gene expression, splicing, reverse transcription, capping of messenger RNA, internal initiation of protein synthesis, processing of membrane proteins through the Golgi apparatus, and the identification of oncogenes, were all initially uncovered through studies of viruses.

The medical challenges posed by viruses and microbial pathogens remains enormous. Despite the availability of potent antimicrobial drugs, microbial pathogenesis gives rise to severe complications including blindness, paralysis, and neurological defects and can lead to chronic diseases including cancer, heart, lung or kidney disease. Recently, the challenges posed by infectious disease have been exacerbated by the emergence not only of new pathogens, such as the SARS, AIDS and West Nile Viruses, but also of generation of new bacterial and viral strains that display increased resistance to antimicrobial drugs. It is only by developing a thorough understanding of the biology of pathogenic microbes, their host organisms, and how the two interact during infection that improved strategies for prevention and treatment of infectious diseases can be achieved.

Current faculty in the Department of Molecular Biology and Microbiology includes 11 primary faculty members and 14 adjunct faculty. Our distinguished faculty have successful nationally-funded research programs and publish in the most prestigious journals. Many serve on study sections for the NIH, serve as editors of journals and take leadership positions in throughout the Medical School. We also enjoy numerous collaborations with faculty in the Departments of Biochemistry, Neuroscience and Genetics, the Case Comprehensive Cancer Center, the Center for AIDS Research, and the Center for RNA Molecular Biology. All these activities create a vibrant scientific environment.

There is a tremendous synergy among our faculty as we initiate new programs in microbial pathogenesis and virology that utilize genetic and molecular analysis of microorganisms. A common technical theme running throughout the Department is the use of fluorescent microscopy to image molecules within cells. Applications range from the localization of viral proteins within eukaryotic cells to polar structures with bacterial cells. Another important theme that defines our work is the use of genetic tools to rigorously study the molecular biology of microorganisms. With the completion of the genome sequence for a vast array of organisms, including man, the availability of transgenic animals with specific immunological defects, and advances in bacterial and viral genetics, we are in a unique position to understand the genetic basis for bacterial and viral pathogenesis. The development of multidisciplinary programs that provide for productive interactions with our clinical colleagues studying infectious diseases and exploit genetics, microbiology, and modern biochemistry, including structural biology, in the study of micro-organisms will be the key to our long-term success.

The Department is currently in a period of rapid expansion. The School of Medicine has made a strong commitment to faculty recruitment the areas of molecular virology and in bacterial development and pathogenesis. The Department has successfully recruited six outstanding new junior faculty since I arrived in July 2002:

Dr Erik Andrulis, who arrived in July 2003, is studying how incorrectly processed RNA is recognized and removed from cells, a process called RNA surveillance. Dr. Andrulis is linking the exosome, a key factor in the RNA surveillance machinery, to the cell division cycle.

Dr Catherine Patterson, who arrived in December 2003, is studying how viruses are recognized and cleared from neurons. She made the important discovery that measles virus can induce chemokine synthesis in neurons. Similar mechanisms may apply to all viruses that infect the central nervous system, including West Nile virus.

Dr Patrick Viollier, who arrived in July 2004, and is researching the genetics of differentiation and pilus development in bacteria. His work strongly complements that of Dr Piet de Boer and is providing new insights into the mechanisms of bacterial pathogenesis.

Dr David McDonald, who arrived in September 2004. Dr McDonald is an expert in fluorescent deconvolution microscopy. He has pioneered the use of this technique to study HIV infection and spread from dendritic cells to T cells.

Dr. Arne Rietsch, who arrived in December 2005, is researching the genetic control of the type III secretion apparatus, in the bacterium Pseudomonas, the major bacterial pathogen in cystic fibrosis.

Our newest recruit is Dr. Liem Nguyen, who arrived in December 2006. Liem is working on the interactions between mycobacteria and host mammalian cells, as well as investigating the molecular basis for drug resistance in MTB.

The rapid pace of faculty recruitment gives us some of the feel of a biotech start-up. If you are here for a year, you are already one of the old timers! Our faculty expansion will continue over the next several years. We currently have active searches targeting a senior cancer virologist, as well as additional junior faculty studying molecular virology.

In parallel, we have been transforming the physical layout of the Department using innovative designs created for us by our architects, Milan Bender and Associates. Dedicated in December 2003, The Rottman seminar room, named in honor of Fritz Rottman who was the chairman of the Department from 1981 to 1999, provides a state-of-the-art lecture facility. The expansion wing of the Harland Wood building which opened in March 2003, has provided us with 6300 sq. ft. of new research space and departmental equipment space housing our molecular imaging equipment and centrifuges. A large multi-investigator tissue culture facility (including BL2 containment laboratories) opened for business in February 2004. An upgraded media preparation kitchen was completed in November 2005. We are currently upgrading 4500 sq. ft. of new research space which will be devoted to virology.

Traditionally, the Department has had outstanding postdoctoral and graduate student training programs. Most of our trainees have become faculty at prestigious universities here and abroad, while others have become notable scientific leaders in the biotechnology and pharmaceutical industries. One of our recent “stars”, Dr. Thomas Bernhardt, won the prestigious Burroughs-Wellcome Fellowship and will be starting as an Assistant Professor at the Harvard School of Medicine in March 2007.

We currently offer two different Ph.D. degrees, our traditional program in Molecular Biology and a program in Molecular Virology, a unique multi-departmental program drawing on faculty from many departments at Case Western Reserve University and the Cleveland Clinic Foundation (Dr. Philip Pellett, Director of Studies).

We look forward to the continued expansion of the Department, and most importantly to continuing scientific excellence in the coming year!

Jonathan Karn, Ph.D.

Spring 2007