Douglas Clark

Douglas Clark

Professor, Chemical Engineering

497 Tan Hall
Mailcode MC 1462
UC Berkeley

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Research Areas


Research Interests

Professor Clark's research is in the field of biochemical engineering, with particular emphasis on enzyme technology and bioactive materials, extremophiles (microorganisms that have adapted to harsh living environments) and extremophilic enzymes, cell culture and metabolic flux analysis, and bioremediation. Much of the Clark group's recent research involves the development of new enzyme systems that have practical applications, from drug discovery to large-scale bioprocesses in industry. For example, Professor Clark's group has devised ways to greatly increase the activity and stability of enzymes under conditions suitable for the synthesis of chemicals and pharmaceuticals, namely under high temperature and pressure, and/or in organic solvents. These developments are particularly important for the large-scale application of enzymes in the pharmaceutical, chemical, and agrochemical industries.Clark and co-workers also pioneered the development of combinatorial biocatalysis, a technique that uses enzymes and microbes to derive small-molecule lead compounds from a common starting compound. Combinatorial biocatalysis is an emerging technology in the field of drug discovery. The biocatalytic approach to combinatorial chemistry uses enzymatic, chemoenzymatic, and microbial transformations to generate libraries from lead compounds, which can then be screened to check for a desired activity. Current combinatorial biocatalysis projects involve the generation of potential anti-cholesterol agents using unique compounds produced by a deep-sea organism as a starting point, and the biocatalytic synthesis of new anti-HIV compounds. The group is also developing microfluidic bioreactors and enzyme microarrays for carrying out high-throughput combinatorial biocatalysis on a microscale. The Clark group is also trying to find ways to practically exploit microorganisms that have been isolated from extreme environments, such as hydrothermal vents that lie deep in the ocean. These versatile organisms, known as extremophiles, are able to grow and survive in harsh environments and could therefore be adapted to catalyze reactions in the broad range of process conditions that are used in industry. For this research, Clark and his group have built specialized equipment that can duplicate the most extreme conditions on Earth that are known to support life, i.e., high temperatures and greatly elevated pressures. By studying extremophiles under these conditions, the Clark group has been able to examine mechanisms by which these robust organisms adapt to stressful extremes, and explore new bioprocesses at the outer limits of life. Another major activity within the Clark Group, in collaboration with Professor Blanch, concerns the monitoring and modeling of complex metabolic reaction networks in breast cancer cells. This research involves the use of a relatively new technique, metabolic flux analysis, to study the major metabolic pathways, and complex interactions among them, in cancer cells under different growth conditions and treatment regimens. This approach therefore enables comprehensive examination of cancer-cell metabolism, and may reveal drug targets for new therapies to control cancer cell proliferation.