Monthly Seminar Program Guest Speakers: Professor Vicky Buchanan-Wollaston Dr. Katherine Denby Dr. Till Bretschneider Research Fellow Speaker: Dr. Chris Penfold Phd Speakers: Emily Breeze Lesley Foster Anthony Knight October 12, 2012 Seminar program Time 13:10-14:00 Session Guest speaker Location MOAC Seminar room 14:00-14:50 Lunch Common room 14:50-16:00 3 Phd Presentations Phd presentations consist 15 minute talks (including questions) audience rotates between three rooms Emily Breeze Lesley Foster Anthony Knight MOAC Seminar Room WSB 325 WSB 336 16:00-16:20 Break Common room 16:20-16:45 Research Fellow talk Christopher A Penfold MOAC Seminar room Wine and Cheese Common room 16:45 1 Presentation Description Guest Speaker Session Introduction to the seminar series followed by three short talks from Vicky Buchanan-Wollaston, Katherine Denby and Till Bretschneider on their take on Systems Biology and how it applies to their research. Research Fellow Session Christopher A Penfold Is a research fellow working on the PRESTA project, which aims to identify a core stress-response network in the model organism Arabidopsis thaliana using systems biology. His research includes developing methods for analysing genome scale time series data, including network inference algorithms that can learn from multiple (time-series) datasets. Phd Session 1: Emily Breeze Action of NF-Y transcription factors in plant stress responses Global food security is one of the prominent challenges facing mankind in a world of increasing population and changing climate. Environmental stresses, such as drought, high salinity and pathogen attack, cause significant crop losses worldwide. Consequently, plants have evolved complex and highly regulated stress response mechanisms. Although there are certainly stimuli-specific pathways, many genes appear to be induced by multiple stresses supporting the existence of a common core stress response transcriptional network. The PRESTA project aims to elucidate this stressresponsive regulatory network. The NF-Y (Nuclear Factor Y) transcription factor family are likely key regulators in multiple stress responses. NF-Y functions as a heterotrimeric complex consisting of NF-YA, NF-YB and NF-YC subunits which, in Arabidopsis, are encoded by multigene families that could theoretically combine into 1690 unique TFs. This combinatorial diversity could enable fine-tuning of transcriptional regulation by activating specific groups of stress-responsive genes. My project aims to identify functional NF-Y complexes involved in regulating plant stress responses and to elucidate the direct downstream targets and upsteam regulators. I am currently using network inference, together with yeast-1 and 2-hybrid assays and microarray analysis of altered expression mutants to generate and test small-scale networks centred around a subset of key regulatory NF-Y subunits. 2 Phd Session 2: Lesley Foster Alternative Splicing in Plant Defence Alternative splicing in plants is emerging as a key component of posttranscriptional control, fine tuning gene expression and increasing proteome complexity. Understanding the mechanisms behind AS may enable plant engineering to be carried out at the finer level of post translational control, enabling production of plants with increased disease resistance and helping to maintain food security in the 21st century. Following on from completion of my mini project in this area I will discuss problem encounters and how I plan to build on this work during my Phd. Phd Session 3: Anthony Knight Modelling the kinetics of GPCR pharmacology The ability of cells to perceive and respond to changes in their microenviroment is an essential prerequisite of life. Many extracellular signals are detected through G protein-coupled receptors (GPCRs) that couple to hetertrimeric G proteins consisting of a Gα, Gβ and a Gγ. Stimulation of a GPCR causes dissociation of the heterotrimeric G protein and regulation of downstream effectors to bring about a myriad of responses. G proteins, and the downstream pathways activated are defined by their Gα subunit. GPCRs can couple to various G proteins and which G protein is activated can be influenced by ligand. This is termed functional selectivity and is of growing interest to the pharmaceutical industry. Understanding the kinetic processes of functional selectivity can help design more specific drugs with fewer side effects. However studying this effect in mammalian cells is difficult due to cross talk between many signalling pathways and shared components. To study functional selectivity in individual GPCR-Gα interactions we turn to a simple model system, the Saccharomyces cerevisiae pheromone response. Through altering the five Cterminal amino acids of the Sc. cerevisiae pheromone response we can study a mammalian GPCR-Gα interaction without the complexity of mammalian systems. Using a Systems Biology approach we can elucidate the kinetic parameters of GPCR pharmacology. Through computationally modelling these chimeric yeast strains and fitting to the experimental data of a number of mammalian GPCRs we can determine kinetic parameters that we cannot measure directly. Our initial studies focus on the adenosine receptor family. 3