Centre for Biomolecular Sciences External Seminar Programme 2008-09 Thursday 25th February 2010 CBS II-A150 Lecture Theatre, 13:00-14:00 Prof. Stephen Bell (Oxford University) DNA replication and Cell Division in the third domain of life Stephen Bell Sir William Dunn School of Pathology Oxford University In the talk I will describe our studies of Sulfolobus, a hyperthermophilic crenarchaeal genus. In common with other archaea, they have transcription and replication machineries that resemble an ancestral form of the eukaryotic apparatus. The relative simplicity of the archaeal replication machinery has facilitated the biochemical analyses of replication proteins. Further, although prokaryotic, Sulfolobus has three replication origins per chromosome and these fire in all cells. The firing of all three origins occurs within a narrow temporal window in the archaeal cell cycle, closely following cell division. With regard to cell division Sulfolobus lacks homologs of the actin and tubulin superfamily and yet undergoes cell division by a canonical binary fission mechanism. We have recently identified archaeal orthologs of the eukaryotic ESCRT apparatus as key components of the cell division apparatus, shedding light on the ancestral role of this conserved membrane manipulation system. 1 Thursday 11th March 2010 CBS II-A150 Lecture Theatre, 13:00-14:00 Dr. Ariel Blocker (Bristol University) Type III secretion systems: from function to structure to applications Ariel J. Blocker, Ph.D. Senior Lecturer in Microbiology Departments of Cellular & Molecular Medicine and Biochemistry School of Medical Sciences University of Bristol University Type III secretion systems (T3SSs) are essential virulence devices for many gram-negative bacterial pathogens of humans, animals and plants. They serve to translocate virulence effector proteins directly into eukaryotic host cells. T3SSs are composed of a large cytoplasmic bulb, containing the export apparatus, and a transmembrane region into which a needle is embedded, protruding above the bacterial surface and terminated by a distinct tip. My group has studied this nanomachine using a variety of cell biological, biochemical and structural approaches. Our work has led to substantial novel mechanistic insights into the function of these systems, which we are now using to progress further and also to develop new prophylactic and therapeutic tools against the bacteria that carry them. These may well become new broad-range anti-virulence treatments at a time when antibiotic resistance continues to spread. 2 Wednesday 24th March 2010 CBS II-A150 Lecture Theatre, 13:00-14:00 Prof. Jerry Wells (Wageningen University, Netherlands) Microbial TLR signalling in the gut and homeostasis Jerry Wells Wageningen University, Netherlands The mucosal surface of the GI tract is in close proximity to the large number of commensal and symbiotic bacteria and is also the major portal of entry for pathogens. Innate pattern recognition receptors such as the Toll-like receptors recognize both pathogens and non-pathogens thus creating a unique regulatory challenge for the mucosal immune system. The role of Toll-like receptors in the homeostasis of tolerance and immunity in the gut and evidence for new homeostatic mechanisms will be presented. 3 Wednesday 31st March 2010 CBS II-A150 Lecture Theatre, 13:00-14:00 Prof. Mike Sutcliffe, FRSC (Manchester University) DNA replication Dynamically-coupled Enzyme Catalysis: Insight from Simulation Mike Sutcliffe School of Chemical Engineering and Analytical Science University of Manchester Enzyme catalysis is inherently a dynamic process, with the catalytic step involving atomic fluctuations which lead to bonds being broken and new ones formed. Protein structures determined from X-ray crystallography and NMR spectroscopy have provided important insight into the form and function of enzymes, yet they give only brief snapshots into the life of a protein - very little is known about dynamic processes that trigger catalysis. This presentation will illustrate how simulation has been used - synergistically with structural and kinetic studies - to provide an atomistic description of the link between internal enzyme motions and catalysis. 4