Our group studies enzymes that degrade toxic compounds, of several sorts. Compounds made all the time in our bodies for which we have natural defenses, and compounds found in the environment for which we do not have evolved defenses. In the process of using oxygen to extract energy from food, we make toxic bi-products, especially superoxide. To defend against this, aerobic organisms possess superoxide-metabolizing enzymes called superoxide dismutase. Our group is studying superoxide dismutase to learn how this robust little enzyme can survive its toxic substrate, and still turn over some 25,000 times per second. We would like to bring this high resilience and activity to bear in practical problems including synthesis of new antibiotics and degradation of PCBs. Thus, we have engineered a couple of promising mutants of superoxide dismutase that we are developing for practical bio-engineering and bio-remediation purposes.
Our other enzyme degrades TNT. This enzyme, "nitroreductase" was isolated from bacteria growing in a weapons storage dump. We find that it has the ability not only to degrade TNT, but other serious toxins as well, including herbicides and pesticides that constitute persistent toxins in soil, as well as residues on food. In this case, we already have the chemical repertoire we need in the naturally-occurring enzyme, but we need to better understand its range of stability, so that we can learn what conditions it would need for use in practical settings.

Mutants of an ancient enzyme that display novel activity.
Our research on superoxide dismutase (SOD) has laid a foundation for designing new catalytic activity into this robust well-understood active site. In this project, the student would work with a mutant of SOD which has the ability to accelerate degradation of PCBs, by catalyzing the crucial ring-opening step. The objective would be to prepare a quantity of this enzyme following established protocols, and assess its ability to degrade a number of different compounds related to PCBs (but not toxic).

Converting Mn-requiring superoxide dismutase into a Fe-utilizing superoxide dismutase
Just as philosophers of old wanted to change lead to gold, bacteria have often found themselves in an environment rich on one metal ion, when they needed another. Similarly, cellular organelles that rely on Mn ions to support superoxide dismutase (SOD) protection from oxidative stress and death, often experience excess Fe, and Fe incorporation into SOD instead of the Mn they need. We have designed a mutant SOD protein which we believe will be active with Fe, as well as Mn. We seek a student to purify this protein and test its activity with each of the two metal ions.

Nuclear Magnetic Resonance of an explosive - degrading enzyme
We have a very active project investigating an enzyme that can metabolize a wide variety of explosives and pesticides. We seek a student who would help us in purifying quantities of this enzyme with a special probe incorporated to facilitate studies by nuclear magnetic resonance. We plan to use this strategy to learn about how this enzyme may have a flexible structure (eg. a bean bag chair) to bind a wide array of toxins, as opposed to the fixed structure (eg. a wooden desk chair) that is usually assumed for other enzymes.