Gene Regulation
I am interested in proteins that regulate gene expression in bacteria. In recent years, the main focus has been on regulators that respond to nitric oxide (NO), which is an intermediate of the denitrification pathway, and is made by host immune cells to counteract invading pathogens. My work has helped to define the DNA binding specificities of four transcriptional regulators from E. coli: FNR, NorR, NsrR and FeaR.
Denitrification
Denitrification is the respiratory reduction of nitrate to dinitrogen, via the intermediates nitrite, NO and nitrous oxide. Denitrification is a route for the loss of fixed nitrogen from agricultural soils, is a means to remove nitrate in waste and water treatment processes, and is a significant source of nitrous oxide, which is an important greenhouse gas. We use Paracoccus denitrificans as a model organism for denitrification, and our current focus is on the relationship between respiratory metabolism and surface-attached growth.
Nitric oxide
Denitrifying bacteria make and consume NO through the activities of nitrite reductase and NO reductase, respectively. Pathogenic bacteria are exposed to NO made by host cells and, in many cases, express NO-inducible NO detoxification enzymes. We are interested in bacterial responses to NO – the regulators involved and the roles of the genes that show NO-sensitive expression patterns.
Methylotrophy
P. denitrificans has also been used as a model for the study of methylotrophy - the utilization of methanol, methylamine, formaldehyde, and formate as sources of carbon and energy. These one-carbon compounds are oxidized to carbon dioxide which is then assimilated via the Calvin Benson cycle in this organism. Our main focus is on the regulatory mechanisms that control the expression of genes involved in methylotrophy. There is interest in the synthetic biology community in developing methylotrophs that synthesize valuable products while growing on inexpensive and readily available substrates.
Research in my lab has been funded by the National Institutes of Health, National Science Foundation, Biotechnology and Biological Sciences Research Council and Natural Environment Research Council.