Biological Hydrogen Production
Synechocystis PCC6803, a cyanobacterium, is used both as a platform for photobiological H2 production and as a simple model system for the study of photosynthesis. The metabolic engineering of Synechocystis PCC6803 strains with the capability of consistent high yielding photobiological production of H2 requires the continued development of comprehensive mathematical models describing the metabolism underlying H2 production and linking genomic, proteomic and metabolomic information. Such models help organize disparate hierarchical information, discover new strategies, and understand the essential qualitative features of components and interactions in a complex system. The goal of this project is to develop metabolic reconstruction models of Synechocystis PCC6803 using metabolic flux analysis and associated modeling techniques. This work is funded through the Department of Energy (R. Ely, PI; http://www.bioe.orst.edu/Faculty/Ely/index.htm)
Microbial Community Structure
Human population growth and the associated increase in greenhouse gas production, nutrient flux and pollutant discharge can substantially affect microbial production and cycling of organic and inorganic materials. The importance of microbial diversity to ecosystem resistance to alteration may be inferred from well-established theories of the consequences of decreased biodiversity on ecosystem resilience to modification. The goal of this research is to develop general mathematical modeling approaches for assembling microbial communities from function-based building blocks. Although the high-level approach is conceptually similar to that found in the field of synthetic biology, it is executed at the microbial community scale, with whole organisms and using analytical tools from metabolic engineering.
Biosensor Systems
False positives and negatives are issues limiting the use of biosensor systems for environmental screening and other applications. The development of robust bioinformatics and pattern recognition approaches for classifying biologically active agents is therefore necessary. Integrated experimental and analytical approaches for the automated classification of biologically active agents using both cell-based and microbial systems are being developed (US 7,132,242; US 6,913,877; Patents Pending; http://oregonstate.edu/research/technology/index.htm; http://oregonstate.edu/research/technology/technos/os98-32.html).
Past Research
Diabetes Metabolism
Methylglyoxal, a toxic metabolite associated with chronic long-term illnesses found in sufferers of diabetes mellitus, has recently identified as a signal molecule intimately involved in caspase-independent but Reactive Oxygen Species dependent mechanisms regulating apoptosis or programmed cell death. The application of quantitative mathematical models derived from kinetic expressions that simplify the complexities of living systems is an important area of bioengineering research that can make significant contributions to the study of metabolism and disease states. The goal was to perform physiological studies within a framework of modeling tools provided by metabolic engineering. These tools have played a vital role in elucidating complex metabolic interactions, understanding in vivo reaction kinetics and analyzing the effect of genomic or environmental changes on cellular responses.
MacDonald, M.J., Chaplen F.W.R., Triplett, C.K., Gong, Q., Drought., H. (2006) Stimulation of insulin release by glyceraldehyde may not be similar to glucose. Arch Biochem Biophys, 447(2):118-26.
Kingkeohoi, S. and Chaplen F.W.R. (2005) Analysis of methylglyoxal metabolism in CHO cells grown in culture. Cytotechnology, 48:1-13.
Sharma, V., Narayanan, A., Rengachari, T., Temes, G.C., Chaplen, F.W.R. and Moon, U. (2005) A low-cost, portable generic biotoxicity assay for environmental monitoring applications. Biosensors and Bioelectronics. 20(11):2218-27.
Clark, K.J,, Chaplen, F.W. and Harcum, S.W. (2004) Temperature effects on product quality related enzymes in batch CHO cell cultures producing recombinant tPA. Biotechnol. Prog. 20(6):1888-92.
Van Herreweghe, F., Mao, J., Chaplen, F.W.R., Grooten, J., Gevaert. K., Vandekerckhove, J. and Vancompernolle, K. (2002) Tumor Necrosis Factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of specific methylglyoxal-derived AGEs. Proc. Natl. Acad. Sci. USA, 99(2):949-54
Chaplen, F.W.R., Fahl, W.E., and Cameron, D.C. (1998) Evidence of High Levels of Methylglyoxal in Cultured Chinese Hamster Ovary Cells. Proc. Natl. Acad. Sci. USA, 95(10):5533-5538.
Chaplen, F.W.R., Fahl, W.E., and Cameron, D.C. (1996) Effect of Endogenous Methylglyoxal on Chinese Hamster Ovary Cells Grown in Culture. Cytotechnology 22:33-42.
Chaplen, F.W.R., Fahl, W.E., and Cameron, D.C. (1996) Method For Determination of Free Intracellular and Extracellular Methylglyoxal in Animal Cells Grown in Culture. Anal. Biochem. 238:171-178.
Chaplen, F.W.R., Fahl, W.E., and Cameron, D.C. (1996) Detection of Methylglyoxal as a Degradation Product of DNA and Deoxyribonucleotides Treated with Strong Acid. Anal. Biochem. 236:262‑269.