Wayne Hynes, Ph.D.
Department of Biological Sciences
College of Sciences
Old Dominion University, Virginia

Project Title: The role of defensin in the transmission of Borrelia burgdorferi

Project Cost: $60,000

Ticks are able to transmit a number of disease causing bacteria, but yet they do not become sick themselves.  This is in part due to the production of antimicrobial proteins, known as defensins, that form holes in the bacterial membrane and kills the cell.  Defensin proteins are found in the hemolymph (blood) of the dog tick but not in the hemolymph of the deer tick. This difference may, at least in part, explain why the deer tick but not the dog tick is able to transmit the bacterium borrelia burgdorferi, the causative agent of Lyme disease.  Dr. Hynes proposes to determine whether defensin plays a role in the inability of the dog tick to transmit this microbe.  This will be done in preventing expression of the gene encoding the defensin in dog ticks using RNA interference.  By interfering with the ability to produce defensin, he will address questions relating to how bacteria survive in hemolymph, and whether are they to make it through the “blood” to the salivary glands where they can be transmitted to another host, such as man.

Expected Date of Completion:  December 2008

Brian Stevenson, Ph.D.
Department of Microbiology, Immunology and Molecular Genetics
College of Medicine
University of Kentucky

Project Title: Studies into the mechanism of Borrelia burgdorferi vIsE recombination
Project Cost: $60,000

The causative agent of Lyme disease, Borrelia burgdorferi, can infect humans and other animals for many years, perhaps even a lifetime.  It is thought that the bacteria’s vIsE gene plays an important role in long term infection.  During infection, the DNA sequence of the bacteria’s vlsE gene changes, due to replacement of certain DNA sequences from others supplied elsewhere in the bacteria’s genome.  The mechanism by which this occurs is not yet known, but its identification will be an important step toward understanding the ability of this pathogen to infect humans and will lead to improved, novel therapies for treatment of Lyme disease. B. burgdorferi makes at least one protein that binds to a specific region of DNA in the vlsE gene.  Dr. Stevenson proposes that this protein plays an important role in vlsE recombination.  In this project, he will identify this protein(s) and precisely define the DNA sequence within vlsE that binds the protein(s), then develop mutant bacteria that will permit examination of the effects that preventing protein-DNA interactions have upon vlsE recombination.

Expected Date of Completion:  December 2008

Jason Anderson Carlyon, Ph.D.
Department of Microbiology, Immunology and Molecular Genetics
College of Medicine
University of Kentucky

Project Title: Identification of novel Anaplasma phagocytophilum adhesions and receptors
Project Cost: $60,000

Human granulocyctic anaplasmosis (HGA) is an emerging potentially lethal disease and the second most common tick-transmitted infection in human in the United States.  HGA is caused by the bacterium, Anaplasma phagocytoplilium that also affects dogs, sheep and horses.  After being transmitted to a human by the bite of an infected tick, A. phagocytophilium invades a specific type of white blood cell called a neutrophil.  The ensuing disease is characterized by symptoms that include fever, malaise, anemia, and impaired immune responses.  The susceptibility of neutrophils to A. phagocytophilium is due to precise molecular interactions that occur between the bacterium and the host neutrophil.  Essentially, A. phagocytophilium presents an array of “keys” (called adhesins) on its surface that interact with certain “locks” (called receptors) on the neutrophil surface.  These interactions “open the door” for the bacterium to invade its host cell and cause disease.  Dr. Carlyon is working to discover the A. phagocytophilium adhesions and the neutrophil receptors that they bind as a means for identifying new targets for therapies or vaccines for treating or preventing HGA, respectively.  This work has the potential for developing treatments against other tick-borne diseases caused by pathogens related to A. phagocytophilium.

Expected Date of Completion:  December 2008

Patricia J. Holman, Ph.D.
Department of Veterinary Pathobiology, College of Veterinary Medicine
Texas Agricultural Experiment Station
Texas A & M University

Project Title: Babesia microti: in vitro culture and molecular interaction between parasite and host receptors at invasion
Project Cost: $60,000

Babesia microti is a blood parasite and is the most common cause of a disease called human babesiosis in the United States.  There are no tests for this parasite in donated blood or organs so babesiosis has resulted from transfusions or transplanted organs from infected people.  Dr. Holman will develop a method to culture these parasites, which help us design diagnostic tests, drugs for treatment and vaccines.  They will also allow us to study how the parasite gets into the red blood cell.  The exact way these parasites recognize and adhere to a cell in order to enter it is not yet known.  We will study a protein on the parasite called apical membrane antigen 1 (AMA-1) that binds with the red blood cell in order to infect the cell.  Using state of the art molecular technology, we will identify the exact red blood cell component that binds with the parasite AMA-1.  This study will provide valuable knowledge of the interaction between b. microti and the host red blood cell.  This will help us design safe and efficacious drugs for treatment or vaccines by finding a way to stop the invasion of the parasite into the red blood cell.

Expected Date of Completion:  December 2008
 

2005 Grant Winners

Timothy John Kurtti, Ph.D.
Professor of Entomology
University of Minnesota

Project Title: Analysis of global gene expression in Anaplasma phagocytophilium using tiling microarrays
Project Cost: $60,000

Dr. Kurtti will investigate how the parasite Anaplasma phagocytophilum, which invades certain white blood cells when transmitted to humans, survives the drastic environmental differences between warm-blooded mammals and cold-blooded ticks. Using a new genomic technology called microarray analysis, Dr. Kurtti will determine the specific genes that become active depending on whether the bacterium is in tick or human cells. The results of this work will provide crucial supplemental information to the recently completed but unannotated Anaplasma genome, and will advance current understanding of the bacterium’s ability to evade the immune response of its human host. Further, it will likely establish microarray analysis as an important new technology for studying other bacterial pathogens transmitted by ticks.

Expected Date of Completion: December 2005

Nikhat Parveen, Ph.D.
Assistant Professor Microbiology and Molecular Genetics
New Jersey Medical School
University of Medicine and Dentistry at New Jersey

Project Title: Role of alleles of Borrelia burgdorferi in Lyme pathogenesis
Project Cost: $60,000

The investigators in this project will study an outer surface protein of Borrelia burgdorferi, the bacterium that causes Lyme disease. This protein, known as OspC, is thought to play a key role during early Lyme infection. However, some strains of B. burgdorferi contain a defective OspC gene and fail to cause infection in mammals. By studying the wide variation in OspC expression among different strains of the bacterium, Dr. Parveen will attempt to tease out the specific factors that promote its ability to infect and disseminate through human tissues. This work will also have implications for improved diagnostic testing and vaccine development for Lyme disease.

Expected Date of Completion: December 2006

NRFTD Research Projects 2000-2003

Columbia University
     Endowments at Columbia University
          Establishment of General Endowment for Lyme Disease - $50,000
          Endowed Student Fellowship - $75,000
     Projects funded under the direction of Brian A. Fallon**
          NIH Lyme Project - Adjunct Studies - $35,000
          Autism Project - $12,500
          Physician Records Project - $6,000
          SPECT Scan Study - $25,000
          Atypical Lyme Disease in Children - $15,000
          Immunologic Links to Lyme Disease - $15,000
          Definition of Lyme Encephalopathy - $15,000
          Dean’s Tax (10%) on All Projects - $12,350

**Brian Fallon, M.D., M.P.H., M.Ed. is an Associate Professor of Clinical Psychiatry and
Director of the Lyme and Tick-Borne Diseases Research Center at Columbia University. He is also the Director of Columbia’s Center for the Study of Neuroinflammatory Disorders & Biobehavioral Medicine.

Other Projects
     Lyme Disease Foundation Physicians' Handbook - $10,000

© 2005-2007 The National Research Fund for Tick-Borne Diseases, Inc. All Rights Reserved.