The National Foundation for Infectious Diseases (NFID) awarded four infectious disease researchers who are just beginning their careers with its Young Investigator Matching Grants (YIMG). The YIMG program is supported by an educational grant from the Schering Corporation. Awardees will focus their research on a different area of infectious diseases.

The NFID awards match funding from the awardee's host institution and are intended for pilot work leading to further research. A peer review system comprised of members from the Infectious Diseases Society of America and the American Society for Microbiology evaluated the proposals. The awardees and their area of research are as follows:

John A. Blaho, PhD, plans to evaluate the processes which regulate the replication of Herpes simplex virus (HSV). HSV causes a variety of infections in humans, remains latent in neuronal tissue in its host for life, and can reactivate to cause lesions at or near the initial site of infection. While the mechanism of viral reactivation from the latent state is unclear, Dr. Blaho will test his hypothesis that specific chemical modifications are required for the functions of the regulatory proteins which orchestrate HSV replication.

In previous studies, Dr. Blaho discovered a unique modification which occurs on the viral regulatory proteins, called nucleotidylation. "My future research plan is to determine the function of the nucleotidylation reaction in the replication of HSV," said Dr. Blaho. To accomplish this, he will alter the amino acid sequences of the regulatory proteins and put the altered proteins back into the virus. Dr. Blaho believes that the viruses containing the mutations will not grow in the cells. He added, "I am interested in determining the stage of the virus life-cycle at which these blocks to viral replication occur."

Dr. Blaho is currently an Assistant Professor of Microbiology at the Mount Sinai Medical Center in New York. He received his doctorate in biochemistry from the University of Alabama at Birmingham and did his postdoctoral work in molecular virology at the University of Chicago.

Diarrheal diseases are a major cause of death and sickness worldwide. Limited knowledge of host-parasite interactions that occur during infection also hamper the ability to develop vaccines and better therapeutics.

Andrew Camilli, PhD, is hopeful that his study of Vibrio cholerae, the bacterial agent of human cholera, will lead to the discovery of important host-parasite interactions that occur during infection by a diarrheal pathogen and may further research toward antimicrobial drug development.

Dr. Camilli will study a signal transduction system of the diarrheal pathogen Vibrio cholerae that operates during infection of a host animal. He will test his hypothesis that the signal transduction system functions first by signaling to the bacteria that they are in the host and then by activating a set of genes that code for virulence factors.

Dr. Camilli is Assistant Professor of Molecular Biology and Microbiology, Tufts University School of Medicine. He received his doctorate in microbiology from the University of Pennsylvania and continued his postdoctoral work at Harvard Medical School.

Emerging technology has created the potential to genetically transduce hematopoietic stem cells. As the major effects of HIV-1 infection arise from direct and indirect effects on hematopoietic elements, gene therapy offers a novel and potentially useful approach to interrupt the progression and spread of HIV-1 infection in an individual.

David M. Margolis, MD, will study the gene transfer to stem cells of HIV-infected subjects using established protocols for collecting stem cells. As the metabolic state of stem cells is likely to affect both the ability of these cells to accept foreign genes and the ability of stem cells to engraft in a patient, it is important to evaluate the effect of stem cell manipulation on long-term expression of foreign genes. The study will compare the efficiency of several gene transfer systems and the durability of expression of transferred genes, using both tissue culture and small animal model systems.

Dr. Margolis is an Assistant Professor at the University of Maryland Institute of Virology and the University of Maryland School of Medicine. He received his medical degree from Tufts University School of Medicine.

John E. Tavis, PhD, will focus his research on how the hepatitis B virus (HBV) replicates its DNA during an infection. Since HBV copies its DNA by "reverse transcription," a process that does not occur naturally in human cells, it can be targeted for drug development. Dr. Tavis will study the enzyme that causes reverse transcription--the viral polymerase--by mutating it and then determining how these alterations will affect its ability to copy the viral DNA. With this information, he believes that he will define how the activities of the polymerase interact with one another as well as identify novel activities of the polymerase that may be inhibited with new antiviral drugs.

HBV currently infects approximately five percent of the people in the world and in these people the virus replicates in the liver, causing cirrhosis and liver cancer over time. With no effective treatments for HBV infection, Dr. Tavis is hopeful that his research will stop HBV replication as well as reduce the incidence of cirrhosis and liver cancer in chronically infected patients.

Dr. Tavis is Assistant Professor of the Department of Molecular Microbiology and Immunology at St. Louis University School of Medicine. He received his doctorate in molecular and cell biology from Pennsylvania State University and continued his postdoctoral work there and at the University of California, San Francisco.