David W. Murhammer

Research Interests:
biochemical engineering
insect cell culture
bioreactor monitoring

-------------------------------------------------------------------------------

My research focuses on issues relevant to using the baculovirus expression vector system for producing recombinant proteins, using insect cell cultures for the mass production of viral insecticides, using insect cell as a model system for investigating oxidative stress in virally infected eukaryotic cells, and bioreactor monitoring.

Recombinant Protein Processing
We are modifying host insect cells to extend their capacity to process N-linked and O-linked protein glycans. In addition, we are investigating the effect of large-scale bioreactor environments (e.g., dissolved oxygen oscillations and elevated carbon dioxide concentrations) on protein glycosylation by insect cells. This research is being conducted in collaboration with groups in the Department_of_Internal_Medicine (College_of_Medicine) and the Division_of_Medicinal_and_Natural_Products_Chemistry (College_of_Pharmacy) at The University of Iowa and Department of Molecular Biology at the University of Wyoming.

Viral Insecticide Production
We are developing methods to produce viral insecticides in continuous systems that overcome accumulation of the few polyhedra (FP) mutants and defective interfering particles (DIP) characteristic of current continuous systems. DIP and FP mutant accumulation are being overcome by applying novel bioreactor designs and using molecular biology techniques, respectively. This research is being conducted in collaboration with investigators in the Department of Microbiology (College of Medicine).

Oxidative Stress
We are investigating the oxidative stress resulting from the viral infection of insect cells. This research includes the effect of simulated microgravity (using NASA's rotating wall vessels) on this oxidative stress and developing methods of overcoming the stress, including antioxidant enzyme overexpression. This research is being conducted in collaboration with Professor Victor Rodgers' research group in the Department of Chemical and Biochemical Engineering and groups in the Department_of_Radiation_Biology (College_of_Medicine) at the University of Iowa and Department of Molecular Biology at the University of Wyoming.

Bioreactor Monitoring
In collaboration with research groups in the Departments of Chemistry (College_of_Liberal_Arts) and Pathology (College_of_Medicine), we are developing and implementing a variety of sensing technologies to monitor nutrient (e.g., glucose, glutamine, and dissolved oxygen) and byproduct (e.g., lactate and ammonium ion) concentrations noninvasively in real-time. This technology is being applied to rotating wall vessels developed by NASA to simulate microgravity. We are utilizing these vessels to grow prostate cancer cells to provide a model for studying the corresponding disease.

-------------------------------------------------------------------------------

Selected Publications

Saarinen, M.A., Reece, J.S., Arnold, M.A., Murhammer, D.W., "Monitoring and controlling the dissolved oxygen (DO) concentration within the high aspect ratio vessel (HARV)," Biotechnology Progress, in press, May 2003.

Saarinen, M.A., Murhammer, D.W., "The response of virally infected insect cells to dissolved oxygen concentration: recombinant protein production and oxidative damage," Biotechnology & Bioengineering, Vol. 81, pp. 106-114, 2003.

Rhiel, M., Cohen, M.B., Murhammer, D.W., Arnold, M.A., "Nondestructive near-infrared spectroscopic measurement of multiple analytes in undiluted samples of serum-based cell culture media," Biotechnology & Bioengineering, Vol. 77, pp. 73-82, 2002.

Wang, Y., Oberley, L.W., Murhammer, D.W., "Evidence of oxidative stress following the viral infection of two lepidopteran insect cell lines," Free Radical Biology & Medicine, Vol. 31, pp. 1448-1455, 2001.

Wang, Y., Oberley, L.W., Murhammer, D.W., "Antioxidant defense systems of two lepidopteran insect cell lines," Free Radical Biology & Medicine, Vol. 30, pp. 1254-1262, 2001.