On-Going Research Projects Within NEOCB
Threat Agent Detection
Drs. Woolverton and Lavrentovich (Liquid Crystal Institute) in collaboration with Dr. Niehaus (at NEOMED) underpin a multidisciplinary, multi-institutional research project that is the first application of liquid crystalline materials interfaced with traditional immune detection processes to define a real-time biosensor. Patented in 2001, the technology uses liquid crystals (LC) to function as mechano-optical signal amplifiers when interacted with antibodies bound to microbes. This result occurs in real time (minutes), suggesting superior device applications as compared with conventional technology for viable pathogen detection. The project has been funded by the Ohio Board of Reagents (Research Challenge), the National Science Foundation and the Department of Homeland Security.
Electron Beam Technology
Dr. Woolverton, Dr. Roberto Uribe (Program in Electron Beam Technology, KSU) and Dr. Carlos Vargas (Central State University) have an ongoing research project using electron beam technology (EBT) for bioagent threat reduction. The project relates e-beam exposure dose to bacterial endospore killing (so as to define parameters for safe sanitation of mail without its destruction). More recently, they have initiated a second project evaluating the potential survival of DNA from bacteria killed by electron beam irradiation. This second project will elucidate more exact e-beam doses required to prevent lateral gene transfer from killed bacteria to other viable bacteria in the environment. (This project impacts use of e-beam to irradiate foods, human waste, drinking water, etc.) Importantly, The Program in Electron Beam Technology at Kent State has an established track record of working with (and for) industry in a fully operational industrial facility. The EBT program actively engages in academic and industrial research activities; it has secured extramural funding from both federal agencies and industry and is presently involved in projects (CRADA with Oak Ridge National Laboratory) that use electron beams for curing composite materials. The EBT program at Kent State is a visible member of national organizations such as the Council on Ionizing Radiation Measurements and Standards. Active communication has existed with the National Institute of Standards and Technology.
Information Management Architecture
Dr. Austin Melton and Professor Laura Bartolo oversee an interdisciplinary group from Biology, Computer Science and Information Sciences at Kent State University that is developing an advanced, hand-held device that integrates database management and presentation, using a novel (ISO-approved) meta-tagging system to coordinate access to otherwise non-integrated (military, fire, public health, etc.) information sources. The research was initially supported by research challenge funds and is now seeking extramural support. A patent is pending. The group is working on isolating existing features to provide capabilities for detection, diagnostics, and defeat of terrorist threats.
Kent State Imaging, Cell Systems and Visualization Research
Drs. James Blank (Biological Sciences and Biomedical Sciences) at Kent State University leads a multi-institutional (including the Ohio Supercomputing Center), interdisciplinary team of researchers who are defining the microscopy and computing needs to essentially image cellular functions as they happen and process the data and create computer simulations to predict future cell behaviors. This “cellular CAT-Scan” process poses several exciting research questions. The cellular basis of biohazards is critical to understand since the cumulative effects result from altered cellular processes. Through funding by an OBR Research Challenge proposal and two federal allocations, researchers have established core facilities to quantify and evaluate modifications in cell function. A microscopy imaging facility equipped with automated confocal and fluorescent light microscopes allow real-time measurement of altered cellular processes potentially caused by exposure to biohazardous agents. A companion cell systems core facility is equipped for high-throughput quantitative proteomics/genomics to allow for the comprehensive assays to analyze the physiological state of a cell or tissue. Both facilities are linked to a visualization core that contains both high-performance computing equipment and 3D immersive environments to interpret the large data sets produced by the state-of-the-art imaging and cell systems facilities. These core facilities serve faculty focused on three interdisciplinary research areas: The first area, molecular and cell modeling addresses the mathematical and computational modeling of cell behavior and the complex interactions that occur within the cellular environment. The second area, bioinformatics, is focused on mathematical and computational analysis of large biomedical data sets such as that derived from the human genome. The third area, imaging and visualization, is directed at development of quantitative spatial-temporal models for the visualization of biomedical images, particularly those derived from microscopy. These research foci are directly applicable to developing high-throughput testing procedures including interactive software for new systems that detect cellular level responses to biohazards and that provide a the basis for rapid detection. Microbial activities and simulations are also research areas evaluated by the imaging, visualization and informatics projects.
Microbial Control and Drug Discovery
Research efforts of Dr. Robert Bolla at Youngstown State University have identified a novel method for microbial disinfection. The research is related to biopreparedness as two foci. First is the development of a safe, effective method to decontaminate large spaces, following exposure to biological weapons, using a gaseous vapor generated by heating light oils at high temperatures. The heated oil produces a “fog”. Water and oil particles are then “scrubbed” from the fog to produce a gaseous vapor that then can be emitted into a biologically contaminated area. Unlike current methods of disinfection, this method leaves no residue, penetrates paper, is safely applied and is easily vacated once the space is decontaminated. The second focus is to develop a method for oral immunization of animals and humans, particularly those at risk of being infected with zoonotic organisms and high risk of exposure to biological weapons. This research will use genetically modified GRAS (Generally Regarded As Safe) organisms to express the invasion antigens of Shigella flexneri and Salmonella typhimurium. When these GARS organisms are fed to mice or rats, the rodents produce antibodies against the antigens and are protected from subsequent bacterial infection. Dr. Bolla also has modified a plant to express these antigens and again when the plant material is fed to rodents, antibodies are produced and protection provided. Within the NEOCB, the research can expand to include organisms such as Escherichia coli O157:H7.
Dr. Chet Cooper of Youngstown State studies fungi and their potential misuse. Pathogenic fungi possess a variety of attributes that contribute to their overall virulence, i.e., their ability to cause and sustain disease. Some of these properties include noxious toxins and enzymes that could be exploited in developing biological mechanisms to threaten human life as well as agriculture. Using a number of model pathogenic fungi, he is employing modern genomic and proteomic techniques to identify and purify these toxic substances. Once these materials are fully isolated and characterized, he can develop novel chemotherapeutic interventions (e.g., drugs, vaccines, immune modulators, etc.) that will prevent and control infections by pathogenic fungi as well as prohibit the action of their toxins and/or destructive enzymes.
Additionally, Dr. Chun-che Tsai (Chemistry Department) at Kent State University in collaboration with Dr. John Docherty at NEOMED and Dr. Woolverton at Kent State University is exploiting properties of known anti-microbial agents to develop new broad-spectrum drugs for control of infectious diseases. One new class of antiviral agents is modeled after Resveratrol, a grape seed product. A patent is pending. Other synthetic drugs have potent antibacterial activity and research is ongoing.
Advanced Wound Care Projects
Several investigators are working independently on various approaches to control bleeding and deliver antimicrobial agents, anti-cancer agents, growth factors and pain control agents. Dr. David Tuthill at Kent State University uses normal blood clotting factors to control bleeding externally and to deliver growth factors for healing. Dr. Judy Fulton at the Calhoun Research Lab of Akron General Medical Center is engineering skin replacements to facilitate wound healing. Along with Stephanie Lopina (the University of Akron ), Steve Schmidt ( Summa City Hospital , Akron), Bill Landis (NEOMED) and Rose Baker (Akron Children's Hospital), Woolverton, Tuthill and Fulton participate in the Wound Healing Consortium. The consortium is an interdisciplinary team that explores the basic and clinical science issues related to wound healing. The group has evaluated novel dressing materials, antibiotic delivery systems and the use of engineered tissues to facilitate rapid tissue repair.