Bacteria swim by rotating semi-rigid helical flagella. They use motility to move towards optimum environments for growth, which in the case of a pathogen may be the gut wall or a wound and in the case of a symbiont may be its host. As bacteria are too small to sense environmental gradients directly they must use temporal sampling, biasing their overall pattern of swimming in a favourable direction. Chemotaxis and sensory signalling. Bacteria sense and respond to changes in chemicals, terminal electron acceptors such as oxygen and nitrate, light, temperature, osmolarity, pH; integrating the signals to produce a balanced response. A family of receptor proteins sense the change in an environmental stimulus and signal through a cytoplasmic relay of histidine protein kinases and response regulators to control the rotation of the bacterial flagellum. Rhodobacter sphaeroides is a photosynthetic bacterium with a single flagellum. It has a complex and flexible metabolism and over the past few years it has become apparent that its chemosensory pathway is also more complex than that of E.coli, and probably more representative of bacteria in general. We are using R. sphaeroides to investigate (i) the mechanisms involved in controlling expression of the different chemotaxis genes, (ii) the localisation of the different chemotaxis protein homologues to different sites in the bacterial cell, (iii) the segregation of chemotaxis proteins on cell division, (iv) the integration of the different environmental signals, (v) the mathematical modelling of the signalling pathway from the receptors to the flagellar motor. Flagella rotation. We are interested in the mechanics of the flagellar motor in both E. coli and R. sphaeroides. Although the proton gradient is saturating under most conditions, the R. sphaeroides motor stops and restarts, whilst the E. coli motor switches its direction of rotation. We are investigating (i) the copy number and dynamics of individual protein components of the flagellar motor, (ii) the mechanisms involved in driving rotation, (iii) the mechanisms which allow speed change and control stopping or switching of the motor.

Systems Biology. Judy Armitage is also Director of the BBSRC/EPSRC funded Oxford Centre for Integrative Systems Biology. The OCISB aims to bring together researchers from across a wide range of Departments (Mathematics, Computation, Physics, Engineering, Statistics, Chemistry, Pathology, Plant Sciences and Biochemistry) to develop predictive modelling approaches, particularly of cellular signalling networks, to help direct experimental design. For more detail please see http://www.sysbio.ox.ac.uk. Linked to the OCISB is a doctoral training centre in Systems Biology, taking up to 20 graduates a year from all physical and biological science backgrounds http://www.sysbiodtc.ox.ac.uk Collaborative research. 1. As part of the UK Bionanotechnology IRC we are investigating, with Richard Berry in the Physics Department, the biophysics of motor rotation using a range of techniques from molecular genetics through optical tweezers to TIRF microscopy. 2. With Philip Maini in Mathematical Biology we are developing models that explain how bacteria are able to move through different environments and how gradients will alter their patterns of movement with the long term aim of being able to control their migration and thus limit or enhance their ability to colonise certain environments. 3. With Helen Packer at Oxford Brookes University we are investigating the role of motility and chemotaxis in the formation of biofilms by R.sphaeroides using molecular genetics and confocal microscopy. 4. With Antonis Papachristodoulou in the Engineering Department and the IRC, we are utilising computation methods to guide the rational design and construction of novel bacterial signalling pathways for the production of improved biosensors.