APEX Presentations
November 8, 2004
Persistence and efficacy of a Listeria-based vaccination vector in immunocompetent and immunocompromised mice
Name: Elisabeth Hesse
Major: Biology/Biomedical Humanities
Academic Advisor: Dr. Sandy Madar
APEX Advisor: Dr. Brad Goodner
Location: Emory University; Atlanta, GA
Dr. John Roback MD, PhD
Assistant Professor
Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322
404.712.1774
jroback@emory.edu
Source of Funding: Howard Hughes Medical Institute grant number 52003727
Bone marrow transplant (BMT) recipients face complications due to opportunistic infections such as cytomegalovirus (CMV). Vaccination is an effective approach to reduce the risks of infectious disease in immunocompetent individuals. In BMT recipients, however, vaccines must be extremely safe since their immune systems are transiently compromised. Attenuated strains of Listeria expressing an epitope of murine CMV (MCMV) have been developed to vaccinate against MCMV while reconstituting the immune system. The purpose of these studies was to compare the efficacy, persistence, and safety of vaccination strains of Listeria in immunocompetent and immunocompromised mice. The vaccine was found to be both safe and effective in immunocompetent mice. In contrast, immunocompromised BMT recipients infected with Listeria on the day following transplantation experienced high mortality, prolonged Listeria persistence, and generated minimal anti-MCMV immunity. In efforts to improve the safety profile of Listeria vaccination for immunocompromised BMT recipients, we began to investigate alternate methods for delivering Listeria. Using wt mice, we have shown that concomitant ampicillin treatment does not significantly reduce either Listeria persistence or vaccination efficacy. Alternatively, pretreatment of Listeria with a DNA crosslinking psoralen compound completely eliminates Listeria proliferation in wt mice. Ongoing studies are examining the ability of crosslinked Listeria to elicit an anti-MCMV response. Methods that further improve the safety of Listeria immunization, without compromising vaccination efficacy, will be applied to immunocompromised BMT recipients.
Selenite resistance in Agrobacterium
Name: Frank Arnold
Major: Biology/Biomedical Humanities
Academic Advisor: Dr. Matthew Hils
APEX Advisor: Dr. Brad Goodner
Location: Hiram College
Dr. Brad Goodner
Assistant Professor
Hiram College, Hiram, OH 44234
330.569.5260
goodnerbw@hiram.edu
Source of Funding: NSF Microbial Genome Sequencing Program (summer stipend) & Howard Hughes Medical Institute (academic year stipend)
In the process of verifying the identity of the putative Agrobacterium strain UK1, it was discovered that the strain develops a red-orange pigment when grown on media containing sodium selenite. Sodium selenite is used as an antimicrobial agent and very few organisms can thrive in its presence. Upon further investigation, it was discovered that UK1 is a biovar 1 strain of Agrobacterium, so other Agrobacterium strains were tested for selenite resistance. Through the use of basic microbiological, genetic, and microscopic methods, it was discovered that UK1 and other Agrobacterium strains are resistant to high concentrations of sodium selenite, reduce sodium selenite to elemental selenium, form nodules of selenium that are fixed to the cell in some manner, and appear to use the cysteine biosynthetic enzyme sulfite reductase to reduce sodium selenite.
Paying the Toll: The Search for Toll-Like Receptor Activation of NF κ B in Renal Cell Carcinoma
Name: Sarah Zilka
Major: Biology/Biochemistry
Academic Advisors: Dr. Dennis Taylor and Dr. Prudence Hall
APEX Advisor: Dr. Prudence Hall
Location: Cleveland Clinic Foundation Lerner Research Institute Department of Cancer Biology
Dr. Joseph DiDonato PhD
Primary Investigator NB4-30
9500 Euclid Avenue Cleveland, Ohio 44195
216.444.8178
didonaj@ccf.org
The Toll-Like Receptor (TLR) family proteins recognize microbial molecules that initiate pro-apoptotic and anti-apoptotic cascades. In renal cell carcinoma the key signal in anti-apoptotic signaling, Nuclear Factor κ B (NF κ B), is over-expressed and activated, thus bypassing apoptosis and encouraging cell division. The TLR proteins, if stimulated, could cause the abnormal activation of the NF κ B cascade in renal cell carcinoma. In addition abnormal activation of the TLR proteins in bordering normal cells can cause oncogenesis. Using RT-PCR analysis and in situ analysis of various normal and tumor tissue samples, possible signaling pathways can be identified for renal cell carcinoma. Through this analysis of tissue samples TLR 1, TLR 4, TLR10, and Insulin Growth Factor Binding Protein 3 were shown to be over-expressed in renal cell carcinoma, possibly causing the activation of NF κ B.
Equine Dentistry in Practice: A Case Study Comparison
Name: Michelle Hawk
Major: Biology
Academic and APEX Advisor: Dr. Matthew Hils
Location: Village Veterinary Care, Inc.
Dr. Jeffrey Reiswig, DVM, Ph.D
Veterinarian
4159 Hazelton-Etna Rd. , Pataskala, OH 43062
740.927.4159
REISWIG1@aol.com
Routine dental exams are imperative in maintaining good equine health. Horses are prone to a number of dental problems, mostly because their diets have been changed by people. Many of these problems can be prevented or minimized by equine dental work, more commonly referred to as floating in veterinary practice. Two case studies were performed to compare the dental hygiene of a two-year-old paint and a fourteen-year-old Dutch warmblood. The two-year-old had never been bridled and was getting one of its first dental exams and its first float, whereas the Dutch warmblood had never been floated. Both horses were treated similarly with sedation, examination, and subsequent treatment for dental abnormalities. The fourteen-year-old untreated horse had many severe problems, including ulcers, dominant incisors, hooks, and ramps. The two year-old had minor problems that were treated in a routine float. These case studies illustrate the important role of preventive dental care in overall equine health.
The Development, Application, and Enhancement of a Bioinformatics-Based Program for Rapid Gap Closure
Name: Lucas B. Chaney
Major: Biology & Computer Science
Academic Advisor: Dr. Brad Goodner and Dr. Ellen Walker
APEX Advisor: Dr. Brad Goodner
Location: Philips Institute, Virginia Commonwealth University
Dr. Todd Kitten
Associate Professor of Oral and Craniofacial Molecular Biology and of Microbiology and Immunology
VCU School of Dentistry, Wood Building, Rm. 407, PO Box 980566, Richmond VA 23298-0566
804.628.7010
tkitten@vcu.edu
Source of Funding: Bionformatics and Bioengineering Summer Institute supported by the National Science Foundation and National Institutes of
Health
The gap closure phase of prokaryotic genome sequencing projects is typically lengthy and labor intensive. Methods for gap closure that take advantage of DNA sequences in public databases are gaining in utility as the number of available sequences increases. We developed a program called BOX-C (for Blast Organism (X)cross Comparison) to align contigs in the Streptococcus sanguis genome through comparison to the NCBI “nr” database. The program consists of a Perl application utilizing BioPerl, the NCBI Blast program and database, and the Primer3 program to automate the tasks of contig processing, query submission, blastn result analysis, alignment prediction, and primer design. This method identified a number of correct alignments in the S. sanguis genome not suggested by other methods, including comparisons conducted against single genomes of related species. This unique approach combines nucleotide comparison against multiple reference sequences, ease of use, user configurability, and multiple-tool integration. A substantial effort has been made to enhance the accessibility of this tool in order to ensure that other sequencing projects can benefit from its development. Continued advancement in this application and enhancement of access through development of a web portal offers the potential for it to become a mainstay in genome sequencing efforts.
Concept Learning in Brown Capuchins (Cebus apella)
Name: Jennifer Gallerani
Major: Psychobiology
Academic and APEX Advisor: Dr. Kimberley Phillips
Location: Hiram College Capuchin Lab
Dr. Kimberley Phillips
Associate Professor of Psychology and Biology
Hiram College, Hiram, OH 44234
330.569.5229
Phillipsk@hiram.edu
Source of Funding: Howard Hughes Medical Institute
The current study assesses the training component of a match-to-sample task that will ultimately investigate the ability of capuchin monkeys (Cebus apella) to learn the abstract concept ‘identical’. All subjects (n = 4) were experimentally naïve to the testing apparatus as well as to the match-to-sample task. The capuchins underwent a training phase in which they learned to respond to stimuli presented to them via a touch screen monitor. In the training phase subjects were presented with a black rectangle that appeared randomly on either the left or the right side of the monitor. If the subject pressed the rectangle when it appeared it was considered a correct response and the monkey was rewarded with a currant or sunflower seed. If the rectangle presented was not pressed within 10 seconds it was removed from the screen and considered a non-response. Three of the four subjects (mean sessions = 50) respond correctly over 70 percent of the time. One capuchin subject responds correctly approximately 90 percent of the time and will be moved onto a more difficult training task. All subjects have an average correct response reaction time range of 0.5 to 3 seconds during the latter half of the training.