Grant: Operating Grant

Work in my laboratory focuses on Borrelia burgdorferi, the spiral shaped bacterium (spirochete) that causes Lyme disease. This organism has great clinical importance as Lyme disease is the most common tick-borne disease in North America and Europe. B. burgdorferi was discovered only 30 years ago, has many very unusual characteristics and much of how it functions remains unknown. Our interests are in understanding some of the unusual processes as well as the mechanisms by which it causes disease. We are also interested in being able to apply the knowledge we gain to the development of more effective diagnosis, treatment and disease prevention. Our proposed research program is a continuation of our current work: 1) Telomere resolution - the study of how the unusual hairpin ends (telomeres) on the DNA are formed by the telomere resolvase, ResT. This unique process makes an attractive target for drug development. We will further investigate how ResT interacts with other proteins within the cell and its role in the evolution of the unusual linear DNA molecules found in Borrelia species. 2) Antigenic variation - the process whereby the bacterium can stay one step ahead of the host immune system and establish and maintain a persistent infection. We propose to study how this process is regulated and the details of how the surface antigen is changed. 3) Global gene regulation - we have discovered a new gene involved in turning on and off large numbers of B. burgdorferi genes. This new regulatory gene is required for infection in mice and will help us to gain an understanding of the disease-causing process. 4) Genome dynamics - the very lengthy shape of B. burgdorferi presents an interesting challenge for the movement of over 20 DNA molecules a great distance prior to cell division. To study this process we will use a newly developed method (super resolution microscopy) to analyze the movement of these DNA molecules in time and space.