Wolfram Zueckert, MS, PhD
I have a broad background in molecular microbiology, with specific training and expertise in key areas relevant to this research. Postdoctoral training at the Univ. of Pennsylvania (with Howard Goldfine and Dan Portnoy) provided me with the experience in studying the structure-function and enzymatic activities of important
bacterial virulence factors. The remainder of my scientific career, i.e. my dissertation at the Univ. of Basel Biozentrum, postdoctoral training at the Univ. of California at Irvine (with Alan G. Barbour) as well as my independent career at the Univ. of Kansas Medical Center, has focused on Borrelia spirochetes. I was directly
involved in several seminal discoveries, influencing our understanding of the complexity and plasticity of the Borrelia genome, facilitating the structure-function study of heterologous or essential Borrelia proteins, and leading the way in our understanding of B. burgdorferi lipoprotein transport and sorting, thereby elucidating the biogenesis of the spirochetal pathogen interface with the host. Throughout the course of these studies, I and my laboratory members pushed the limits in regard to the genetic manipulation of Borrelia, became proficient in
several protein localization techniques, and explored genomics, functional proteomics and protein structurefunction with support from a local network of experts. In summary, as a laboratory leader and investigator, I have a demonstrated record of successful, productive, and cutting-edge research in an area of high relevance for a common global infectious disease as well as the understanding of basic molecular mechanisms of protein secretion. My role in the current research project optimally leverages my scientific expertise and interest in spirochetal virulence, protein structure-function analysis and functional proteomics.
Lyme Disease and Relapsing Fever Borrelia Spirochetes. We study Borrelia spirochetes and the diseases they cause, Lyme disease and relapsing fever. After transmission of Borrelia through bites of certain tick species, both Lyme disease and relapsing fever are characterized by the spread of bacteria via the bloodstream, which may lead to the infection of multiple organs such as the skin, heart, joints, and brain. While these pathogenic processes are not yet well understood on the molecular level, the involved virulence factors identified so far have been surface lipoproteins.
Protein Secretion in Borrelia. A continuing long-term project identifies lipoprotein sequence determinants, membrane protein complexes and chaperones involved in spirochetal lipoprotein export. We initially used fluorescent proteins as markers for protein localization in live Borrelia cells to determine the sorting signals for surface and subsurface lipoproteins, and have just completed a project that localized the lipoproteome of the Lyme disease spirochete Borrelia burgdorferi. Using cutting-edge molecular genetics and biochemical approaches, we are now in the process of dissecting the lipoprotein export machinery in B. burgdorferi down to the structure-functional level. These studies will ultimately help in the design of novel intervention strategies for spirochetal infections.
Borrelia Lipoprotein Structure-Function. A related research project focuses on the structure-function of the OspC/Vsp surface lipoprotein family that is shared by Lyme disease and relapsing fever Borrelia. Members of this protein family have been shown to be crucial for colonization, tissue tropism and chronic infection of mammalian hosts. The long-term research goals are to define Borrelia-host interactions by integrating functional data and structural information on the proteins involved.