Molecular Genetics Unit

Anthony Pugsley
Our studies focus on understanding the molecular details underlying the fundamental processes of protein traffic and transcription regulation in bacteria, and mainly in Gram negative bacteria.
First, we are interested in the ways proteins are targeted to specific sites in the cell envelope or are secreted into the growth medium. The systems currently under study include the type II secretion systems of Escherichia coli and Klebsiella oxytoca, the E. coli type IV pilus biogenesis system, the biogenesis and localization of lipoproteins in Gram negative bacteria and protein secretion across the outer membrane of Gram positive bacteria belonging to the Actinomycetales family. The structure-function analysis of these systems should provide a greater understanding of the complex machineries that are involved.
Second, our interest in transcription regulation centres on the E. coli transcription activator protein MalT, which controls the expression of genes required for maltodextrin transport and metabolism. MalT is the prototype of a new protein family called the STAND ATPases. We are focusing our attention on the way that positive and negative effectors (maltotriose and ATP, and the proteins MalK, MalY and Aes, respectively) affect the ability of MalT to multimerise and to bind to specific sites in the promoters it controls. These studies are combined with a detailed structural investigation of MalT and its homologues in other bacteria.
All of these studies rely a combination of bioinformatics, genetics, molecular biology, fluorescence, confocal and electron microscopy, biochemistry, biophysics and X-ray crystallography to gain insight into the mechanisms involved.