Susan Lunte, Ph.D., Ralph N. Adams Distinguished Professor of Chemistry and Pharmaceutical Chemistry and Director of the Adams Institute for Bioanalytical Chemistry, Director, Center for Molecular Analysis of Disease Pathways (CMADP), University of Kansas. University of Kansas.
“New enabling technologies at KU for studying disease pathways”
An important mission of the NIH sponsored COBRE Center for Molecular Analysis of Disease Pathways is to provide infrastructure to research investigators in the state of Kansas so that they can perform studies on disease mechanisms that would be difficult to do otherwise. There are three core labs in CMADP. These are the Genome Sequencing Laboratory, the Molecular Probes Core and the Microfluidics and Microfabrication Core. A brief description of each of the cores will be presented, along with some examples of projects that are utilizing the cores. Emphasis will be on the development and use of microfluidics to investigate disease pathways with examples from my laboratory. This includes the development of on-animal sensors and methods for single cell analysis.
Jianming Qiu, Ph.D, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas, School of Medicine
“Bocavirus, a small DNA virus, infects differentiated airway epithelium”
Human bocavirus (HBoV1) is one of the etiological agents of wheezing in young children with acute respiratory-tract infections. We established a reverse genetics system of HBoV1 in 293 cells. Progeny HBoV1 virions generated from this cell line-based production system productively infects polarized primary human airway epithelium (HAE) from both the apical and basolateral sides. Infected HAE showed hallmarks of lung airway-tract injury. Moreover, HBoV1 infection of HAE triggers a DNA damage response (DDR) in infected cells. We discovered that inhibition of the DDR signaling by ATM- or DNA-PK-specific inhibitor significantly reduced virus replication, suggesting a model of DNA repair-facilitated viral DNA replication in differentiated airway epithelial cells. In application of the high apical tropism of the HBoV1 virions, we pseudotyped a recombinant adeno-associated virus 2 (rAAV2) genome of 5.5 kb with the HBoV1 capsid. The rAAV2/HBoV1 chimeric vector was capable of apically transducing HAE at a greater efficiency than rAAV vectors. Thus, we have developed a novel and promising parvoviral vector for gene delivery of human airways.
Juergen A. Richt, Ph.D., Regents Distinguished Professor, Kansas State University College of Veterinary Medicine, Kansas Bioscience Authority Eminent Scholar, Director of the U.S. Department of Homeland SecurityCenter of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD)
“Development of Countermeasures against Zoonotic Pathogens”
The Department of Homeland Security’s Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD) conducts research, develops technology and trains a specialized workforce to help DHS defend US agricultural systems, including developing vaccines for high priority and zoonotic pathogens. In terms of vaccine development, CEEZAD’s focus is on the zoonotic pathogens Rift Valley fever virus (RVFV) and avian influenza virus (AIV). RVFV, a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula has increased interest in RVF vaccines. Sporadic human infections by a novel H7N9 virus occurred over a large geographic region in China in the past 2 years. Human infections with H5N1 have been reported from 15 countries in Asia, Africa, the Pacific, Europe and the Near East since 2003. To this end, vaccine development for RVF centers on the expression of RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in sheep, a target species. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test. Additionally, ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen demonstrated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible. Together, these data indicate a promising vaccine platform for RVFV infection in a susceptible species. In addition, this presentation will show that Newcastle disease virus (NDV)-vectored H7 and NDV-H5 vaccines are able to induce high titers of hemagglutination inhibition antibodies and completely protect chickens from challenge with the novel H7N9 or highly pathogenic H5N1 viruses, respectively.