Research group leaders
We are studying multicomponent assemblies involved in the regulation of the expression of genetic information by controlling the fate of messenger RNA. We hope to understand how such post-transcriptional regulation enables rapid and specific response to developmental or environmental stimuli. In the bacterium, Escherichia coli, RNA turnover and processing is mediated by a multi-enzyme assembly, known as the RNA degradosome. We are exploring the structure and function of the RNA degradosome assembly from E. coli and other bacteria, to understand their multifaceted regulatory functions. The degradosome assembly can target specific transcripts by interacting with non-coding regulatory RNAs, and our structural and biochemical studies are providing insight into the structural basis of this targeted gene silencing. The structure of the catalytic domain in complex with RNA substrate is shown in the figure. This and other structural information has enabled us to propose models for substrate recognition and allosteric activation of components of the degradosome assembly.
We directly visualise the individual components and their complexes at an atomic level using Xray diffraction to reveal the intricate and subtle structures which underlie these complexes. We also use a number of other complementary techniques such as nondissociating mass spectrometry, neutron and X-ray solution scattering, and calorimetry to analyse macromolecular complexes. Through international collaborations, we are studying genetic regulation in vivo, and have obtained evidence for a linkage between RNA metabolism and metabolic state of the cell.
Lab members: Kasia Bandyra, Heather Bruce, Vivian Chan, Daniela Dimastrogiovanni, Dijun Du, Tobbias Gubbey, Steven Hardwick,Xue Pei, Johanna Syrajanen, Jarrod Voss
1. Frank, R.A.W., Titman, C., Pratap, V., Luisi, B.F. and Perham, R.N. (2004) A molecular switch and proton-wire synchronize the active-sites in thiamine-dependent enzymes. Science 306, 872-876
2. Callaghan, A.J., Marcaida, M.J., Stead, J.A., McDowall, K.J., Scott, W.G. and Luisi, B.F. (2005) The structure of E. coli RNase E catalytic domain and implications for RNA turnover. Nature 437 1187-1191.
3. Frank, R.A.W., Kay, C.W.M., Hirst, J. and Luisi, B.F. (2008) Off-pathway, oxygen-dependent thiamine radical in the Krebs cycle. J. Amer. Chem. Soc 130, 1662-1668.
4. Bavro, V.N., Pietras, Z., Furnham, N., Perez-Cano, L., Fernandez-Recio, J., Pei, X.Y., Misra, R. and Luisi, B.F. (2008) Channel-opening and assembly in a bacterial drug efflux machine. Molecular Cell 30, 114-121.