Phase II Research Projects
Research Theme - Infectious Disease
Investigator: Dr. Peter DiMaria, DSU Chemistry
Research Title: RNA Cap Hypermethylases in Microsporidia
Abstract: A number of microsporidia are responsible for serious diseases in AIDS patients and other immune-compromised individuals. In specific aspects of their molecular biology and biochemistry, the microsporidia are highly divergent from other eukaryotic organisms. In general, an understanding of some of these divergent characteristics could be exploited towards the development of better means of diagnosis and treatment of microsporidiosis afflicted patients. The proposed work concerns putative methyltransferases responsible for the hypermethylation of small nuclear RNAs in these organisms. Based on previous studies of microsporidial small nuclear RNA cap structures, these enzymes are likely to be novel in nature. They, therefore, may represent possible targets for anti-infective therapy. The work will involve using bioinformatics approaches to identify microsporidial genes that may encode putative hyperrmethylases. These proteins will be cloned, expressed, and purified. The purified proteins will be assessed for their ability to catalyze the hypermethylation reaction. Additionally, the enzymes will be characterized with respect to the nature of their catalytic activity, identity of product, substrate specificity, kinetic parameters, susceptibility to methyltransferase inhibitors, and catalytically relevant residues.
Investigator: Dr. Lynn Everett, Wesley Sciences
Research Title: Genetic Diversity in Borrelia burgdorferi
Abstract: Borrelia burgdorferi, a tick-borne bacterium, is the causative agent of Lyme disease. There are currently a number of different approaches being used for development of a vaccine to prevent Lyme disease, one of which focuses on OspC, a bacterial outer surface protein. However, over 30 variations of the gene for this protein have been reported. The goal of this project is to aid in vaccine development by identifying the ospC variants of B. burgdorferi present in Delaware ticks. This will be done using PCR to amplify the variable region of the ospC gene, obtaining the DNA sequence of the amplified region, and identifying the variants by computer-aided analysis of the sequences. The feasibility of screening tissue or fluid samples from human patients with Lyme disease in Delaware will also be investigated with an ultimate goal of determining which B. burgdorferi variants are responsible for infection.
Investigators: Dr. Kathleen Curran, Wesley Sciences
Dr. Jonathan Kidd, Wesley Sciences
Research Title: Distribution of Lyme Disease and Other Tick-borne Diseases in Delaware
Abstract: Lyme disease continues to be the most commonly reported tick-borne disease in the United States. Delaware has one of the highest incidence rates for this ailment, yet the distribution of the vector species, the black-legged tick, varies within the state. Some regions have a high density of ticks, with a high infection rate for the disease while other areas have almost none. Additionally, in recent years a number of new diseases have been described, some carried by the black-legged tick, and still others by the lone star tick. Both of these vectors are found in Delaware but the distribution of the newer diseases is unclear. Our goal is to construct a risk assessment map for Delaware for Lyme disease and Human Granulocytic Anaplasmosis, which are transmitted by the black-legged tick; and Human Monocytic Ehrlichiosis and Southern Tick Associated Rash Illness which are vectored by the lone star tick. By using data obtained by collecting ticks from public areas we will be able to clarify the distribution of the vectors, and by testing them for the disease organisms we should determine their prevalence within the state. Additional data provided by veterinarians will identify where dogs are acquiring Lyme. Dogs usually travel less than their owners so they are more accurate in pinpointing local risk.
Investigator: Dr. Diana Haddad, DSU Biology
Mentor: Dr. Leonard Davis, Associate Professor, Biological Sciences, Delaware State University
Research Title: Proteomic analysis of the Plasmodium falciparum gametocyte for malaria vaccine development
Synopsis: Malaria continues to be a devastating disease, affecting hundreds of millions of people living in areas where it is endemic in the developing world. Still, a vaccine and/or other means of effective control of this devastating disease have not been produced. The Malaria genome project reached its goal of completing the sequencing of the genome of Plasmodium falciparum, the species responsible for nearly all malaria deaths in humans. In addition to the parasite's genome, extensive data from its proteome has been made available to the research community. The study proposed here, aims to conduct a large-scale screening of the P. falciparum genome and proteome for the identification and preliminary characterization of genes expressed during or prior to sexual blood stage differentiation and in the process of gametocyte maturation. Although the sexual stages of Plasmodium do not directly cause any symptoms in humans, they are essential for continued malaria transmission and blocking their development would reduce transmission.
A high-throughput approach based on the Gatewayª cloning system will be used to clone a subset (~100 at a time) of selected genes into DNA immunization and expression vectors. DNA immunization vectors and expressed recombinant proteins will be used for immunization of mice and generation of antibodies. The antisera will be used to study expression patterns and subcellular localization in the parasite, namely surface localization of the protein since these proteins are important vaccine candidates. The subcellular characterization studies may lead to the identification of new proteins relevant in transmission to mosquitoes; thus, the implications of these studies for vaccine development are enormous.
