Karen A. McDonald
Professor of Chemical Engineering
B.S., 1979, Stanford University
M.S., 1980, University of California, Berkeley
Ph.D., 1985, University of Maryland, College Park
Profs. Karen McDonald and Alan Jackman are investigating the production of pharmacologically important proteins from plant cell cultures. The research group is studying plant cell cultures of Trichosanthes kirilowii, a member of the Cucurbitaceae family found in China, Japan and Korea. This plant is of particular interest since it is a source of proteins known as ribosome inactivating proteins (RIPs) which have a variety of potentially useful pharmaceutical activities such as antiviral, antitumor, antidiabetic, abortifacient and immunomodulatory. One of these proteins, a 27 kDa protein isolated from the root tuber was found to selectively inhibit viral replication in human blood cells infected with HIV-1. This protein, known as trichosanthin has completed Phase II clinical trials as an AIDS drug. The research group is investigating the kinetics of growth, quantification and characterization of intracellular and extracellular proteins from plant cell cultures and the influences of important bioreactor variables on RIP productivity using natural and genetically transformed T. kirilowii and tobacco cell lines. The ultimate goals of the research are the determination of optimal bioreactor operating strategies to maximize production of functional proteins from these cultures, identify bioprocessing and molecular biological approaches to enhance secretion of these proteins to the culture medium, and to characterize new potential therapeutic proteins. This work has been supported by the National Science Foundation (#BES-9407177), and Universitywide AIDS Research Program (#R94-D-079).
Prof. McDonald is also working on the development of a new
protein expression system which utilizes recombinant plant
viruses in conjunction with plant cell suspension cultures in
vitro. This work is being supported by the National Science
Foundation (#BES-9870453)
N.-J. Remi Shih, K. A. McDonald, T. Girbes, R. Iglesias, A. Kolhoff and A.P. Jackman, "Ribosome-Inactivating Proteins (RIPs) of Wild Oregon Cucumber (Marah oreganus)", Biological Chemistry, 379:721-725 (1998).
Karen A. McDonald, Michael R. Stoner, N. Remi Shih and Alan P. Jackman, "Trichosanthes kirilowii Plant Cell Culture in a 5 Liter Bioreactor" in Plant Cell and Tissue Culture for the Production of Food Ingredients, Edited by T.J. Fu, G. Singh and W.R. Curtis, ACS Symposium, Plenum, NY (In Press).
N.-J. Remi Shih, K. A. McDonald, A. M. Dandekar, T. Girbes, R. Iglesias, A.P. Jackman, "A Novel Type-Ribosome-Inactivating Protein Isolated from the Extracellular Fluid of Transformed Suspension Cultures of Trichosanthes kirilowii", Plant Cell Reports, 17:531-537 (1998).
N.-J. Remi Shih and K. A. McDonald, "Purification and Characterization of Chitinases from Transformed Callus Suspension Cultures of Trichosanthes kirilowii Maxim." Journal of Fermentation and Bioengineering, 84: 28-34 (1997)
Michael R. Stoner, Christopher A. Humphrey, Danielle J. Coutts, N.-J. Remi Shih, Karen A. McDonald and A. P. Jackman, "Kinetics of Growth and Ribsome-Inactivating Protein Production from Trichosanthes kirilowii Plant Cell Cultures in a 5 Liter Bioreactor, Biotechnology Progress 13:799-804 (1997).
N.-J. Remi Shih, K. A. McDonald, A. P. Jackman, T. Girbes, R. Iglesias, "Bifunctional Plant Defence Enzymes with Chitinase and Ribosome Inactivating Activities from Trichsoanthes kirilowii Cell Cultures", Plant Science 130: 145-150 (1997).
A Simplified Procedure for the Purification of Trichosanthin (A Type I Ribosome Inactivating Protein) from Trichosanthes kirilowii Root Tubers, N. Bhatia, K.A. McDonald, A.P. Jackman and A.M. Dandekar, Protein Expression and Purification, 7:143-146 (1996).
Plant Callus as a Source of Biochemicals, K.A. McDonald, A.P. Jackman, J.E. Thorup and A.M. Dandekar, Applied Biochemistry and Biotechnology, 54: 93-108 (1995).
Ribosome-Inactivating Protein Production from Trichosanthes Kirilowii Plant Cell Cultures, J.E. Thorup, K.A. McDonald, A.P. Jackman, N. Bhatia and A.M. Dandekar, Biotechnol. Prog., 10:345-352 (1994).
Bioreactor Studies of Growth and Nutrient Utilization in Alfalfa Suspension Cultures, K.A. McDonald and A.P. Jackman, Plant Cell Reports, 8: 455-458 (1989).
Graduate Students: Raj Krishnan, Masaru Shiratori, Melody Trexler
Undergraduates: Christine Owlett, Devin Eselius
Faculty Collaborators: Alan Jackman, Abhaya Dandekar, Bryce Falk
Professor Alan Jackman, apjackman@ucdavis.edu
Michael Stoner,
A former undergraduate researcher
Danielle Coutts,
A former undergraduate researcher
A wide variety of industrially important compounds are found naturally in photosynthetic organisms and are associated with photosynthetic membranes and/or organelles. We are studying the production of sulfolipids, important due to their anti-tumor and anti-HIV properties, in cyanobacterial cultures in photobioreactors. Production of sulfolipids in cyanobacteria is known to be closely tied to the formation of photosynthetic membranes, which in turn is stimulated under conditions of low light and low nitrogen levels. At high cell densities, however, growth rates of photosynthetic organisms are typically low and limited by light. Thus, optimization of photobioreactor systems for the production of photosynthetic membrane-associated compounds provides a significant engineering challenge to obtain high cell densities in short time periods with high product levels. Profs. McDonald and Jackman are collaborating with other faculty on campus to characterize, quantify, model and optimize the production and product recovery of sulfolipids from cynanobacterial cultures. The overall goals of this research program are to combine biological and bioprocessing approaches to maximize the production of high value, photosynthetically-related compounds (sulfolipids) from cyanobacterial cultures. This work is supported by the University of California Biotechnology Education and Training program.
S.D. Archer, K. A. McDonald and A.P. Jackman, Effect of Light Irradiance on the Production of Sulfolipids from Anabaena 7120 in a Fed-Batch Photobioreactor, Applied Biochemistry and Biotechnology, 67:15-28 (1997).
Production of Sulfolipids from Anabaena 7120 in Continuous Culture, S. Archer, K. McDconald, and A. Jackman, 1995 Annual AIChE Meeting, Miami, FL, November, 1995
Effect of Light on the Production of Sulfolipids Using Cyanobacterial Cultures, (poster with S. Farinha and A. Jackman), Annual AIChE Meeting, San Francisco, CA, November 1994.
Cyanobacteria Photoproduction in a Stirred Reactor: Experiments and Modelling of Growth Under Light-Limited Conditions, (with Y. Ko, B.J. McCoy and A.P. Jackman), ACS Spring National Meeting, Denver, CO, March 1993.
Graduate Students: Seher Dagdeviren
Undergraduate Students: Ruth Chan
Faculty Collaborators: Alan Jackman, Jack Meeks, Bruce German
A major objective of the chemical/petrochemical process industries is to achieve "incident free operation". Currently, abnormal process situations often go undetected by plant operators/personnel until alarms are triggered. Profs. Karen McDonald and Ahmet Palazoglu are working on the development of general techniques for detecting trends in process data and classifying these trends. To facilitate data compression while preserving the main features of the data, they are using wavelet decomposition followed by symbolic representation using fuzzy triangular episodes. Hidden Markov models are used to classify these trends as normal, abnormal or uncertain. The goal of the work is to develop automated methods to detect abnormal process situations as they arise and notify plant operators at the pre-alarm stage. This work is supported by AIGIS Systems.
J. C. Wong, K. A. McDonald and A. Palazoglu, "Classification of Process Trends Based on Fuzzified Symbolic Representation and Hidden Markov Models", J. Process Control (In press).
J. C. Wong, K.A. McDonald, A. Palazoglu and T. Wada, "Application of a Fuzzy Triangular Representation and Hidden Markov Models Classification in the Detection of Abnormal Situations in Refining Processes," Control 97 Proceedings, Sydney, Australia, October 1997, pp 566-571 (1997).
J.C. Wong, K. A. McDonald, A. Palazoglu and T. Wada, "A New Method for Classifying Process Trends Based on Fuzzy Triangular Representation and Hidden Markov Models, IFAC Symposium ADCHEM ’97 Proceedings (In Press).
Mr. Tetsuya Wada, Japan Energy Corporation
The bioprocess engineering laboratories are equiped with fully instrumented bioreactors (two 5-liter New Brunswick BioFlo 3000 with computer interface, a 2-liter New Brunswick Bioflo II continuous bioreactor, several 2-liter New Brunswick Multigen bioreactors, and two 1-liter New Brunswick Multigen bioreactors), a microplate luminometer, an automated ion exchange purification system, gel electrophoresis and electroblotting apparatus, a Hewlett Packard 1050 HPLC, UV-visible spectrophotometers, gas chromatograph, laminar flow hood, sugar analyzer, automated particle counters, centrifuges, temperature-controlled incubators and shakers, and personal computers for data acquisition and data analysis. Other ancillary equipment available in the department includes autoclaves, and freeze dryers. Additional equipment available on campus includes capillary electrophoresis systems, GC-mass spectrometers, PCR systems, DNA synthesizers, and ELISA plate readers.