Annual Report 2009 - Department of Zoology - University of ...

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Cell Biology The Cell Biology group aims to dissect the cellular and molecular networks that regulate animal biology. It focuses on fundamental research in two areas. The first is the mechanisms that regulate cell proliferation and the function of the nucleus. The second is intra- and intercellular signalling. We use a wide range of techniques including molecular, biochemical and genetic approaches, in vivo imaging and the analysis of whole animal function and behaviour. a) DNA Damage and Repair Steve Jackson’s research aims to understand how cells detect DNA damage and signal its presence to DNA repair and cell cycle machineries. Working with both yeast and human cells, his group is identifying new DNA damage response (DDR) factors, defining the functions of known DDR components, assessing how the DDR is affected by chromatin structure, and learning how DDR events are regulated. Rimma Belotserkovskaya: DNA repair and chromatin Jeanine Harrigan: Cell cycle regulation of the DDR Melanie Blasius: DNA damage signalling Pablo Huertas: Double-strand break repair in yeast and Sebastian Britton: DNA damage signalling and repair in humans human cells Abderrahmane Kaidi: The effect of chromatin structure on Ross Chapman: DNA damage signalling and cell cycle the DDR checkpoints Natalia Lukashchuk: Post-translational modifications and Josep Forment: Checkpoint signalling and the DDR DNA damage Yaron Galanty: Post-translational modification of DNA Kyle Miller: Role of chromatin in DNA integrity damage response proteins Tobias Oelschlaegel: Homologous recombination in Simona Giunta: Cell cycle regulation of the DDR mitosis and meiosis Ilaria Guerini: DNA damage response in model organisms Serge Gravel: DNA damage response in yeast b) Regulation of Mitosis Sophie Polo: Chromatin alterations at sites of DNA double-strand breaks Jorrit Tjeertes: Chromatin dynamics in response to DNA damage Jon Pines’ group studies how cells regulate entry to mitosis, and how cells coordinate chromosome alignment and segregation with cell division itself to ensure that the two daughter cells receive an equal and identical copy of the genome. The research focuses on the interplay between protein kinases, phosphatases, and ubiquitin-mediated proteolysis. Because mitosis is a highly dynamic process, the activity, behaviour and proteolysis of proteins in living cells are studied by time-lapse fluorescence microscopy, complemented with biochemical analyses. Philippe Collin: Conditional knockout of APC/C regulators by recombination Barbara Di Fiore: Cyclin A destruction Anja Hagting: Spatial control of APC/C activity Daisuke Izawa: APC/C substrate specificity Mark Jackman: Cyclin B1 and the spindle assembly checkpoint Agata Lichawska: Regulation of mitotic entry Jörg Mansfeld: APC/C through mitosis 15 Paola Marco: Cdk1 and Aurora A regulation of mitosis Takahiro Matsusaka: APC/C substrate selection Oxana Nashchekina: Recombination to tag proteins at their endogenous locus Bernhard Strauss: The role of cyclin B1 in early embryogenesis Felicia Walton: Role of cyclin A in the cell cycle
c) Control of DNA Replication The initiation of DNA replication is a crucial point of regulation in the cell cycle. Errors at this control point or in the processes of replication itself can lead to mutations and other genetic instabilities. Such genetic changes are the driving force behind the development of cancers and the production of genetic diversity, required for evolution. The groups of Torsten Krude, Cath Green and Ron Laskey use molecular and cell biology approaches to study DNA replication and its control in mammalian and amphibian systems. Christo Christov: Regulation of chromosomal DNA replication and cell proliferation Simon Cooper: Screening for novel replication factors Denis Finn: Biochemical analysis of replication protein interactions Timothy Gardiner: Characterisation of Y RNA function in vertebrate DNA replication d) Cell Signalling in Animal Behaviour and Development 16 Sebastian Klinge: Structural and functional analysis of human DNA polymerase/primase Alexander Langley: Characterisation of Y RNA-protein interactions during chromosomal DNA replication Shiphali Shetty: Real time protein-protein interactions at replication forks in vivo Alice Zhang: Characterisation of Y RNA localisation during chromosomal DNA replication We use C. elegans to investigate the molecular networks which underpin the behaviour and development of animals. The group of Howard Baylis focuses on how intracellular calcium signalling networks, regulate the animal’s physiology and development. A recent focus is on the interactions between these pathways and the pathways which cause Alzheimer’s disease. Birgitta Olofsson’s group is investigating how animals evaluate their food and how they use this information to make appropriate modifications to their feeding behaviour. Both groups use a combination of transgenic, molecular and genetic techniques together with quantitative analysis of whole animal phenotypes. Roxani Gatsi: Signalling networks controlling growth Kerrie Ford: IP3 receptor function in C. elegans Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis Jonathon Pines The Cyclin B1-Cdk1 kinase is the catalytic activity at the heart of Mitosis Promoting Factor (MPF), yet fundamental questions concerning its role in mitosis have remained unresolved. Cyclin B1-Cdk1 has been shown to be the key mitotic kinase from yeast, through starfish to frog cells but until now it was not known when and how rapidly Cyclin B1-Cdk1 is activated in mammalian cells, nor how its activation coordinates the substantial changes in the cell at mitosis. This is in part because it has so far proved impossible to synchronise mammalian cells to assay Cyclin B1-Cdk1 biochemically with sufficient temporal specificity. To overcome this limitation we have developed a FRET biosensor specific for Cyclin B1-Cdk1 that enables us to measure its activity with very high temporal precision in individual, living human cells as they divide. This has given is unprecedented insight into how Cyclin B1-Cdk1 controls entry to mitosis. We have found that Cyclin B1-Cdk1 is inactive in G2 phase and activated at a set time before nuclear envelope breakdown. Once activated Cyclin B1- Cdk1 initiates the events of prophase including cell rounding, chromosome condensation, spindle assembly and finally nuclear envelope breakdown. Unexpectedly, we find that Cyclin B1-Cdk1 levels rise to their maximum extent over the course of approximately 30 min and that different levels of CyclinB1- Cdk1 kinase activity trigger different mitotic events. This has revealed how the remarkable reorganisation of the cell is coordinated at mitotic entry by rising levels of Cyclin B1-Cdk1 activity. Reference: Gavet, O. and Pines, J. (2010) Progressive activation of Cyclin B1-Cdk1 coordinates entry to mitosis’. Dev. Cell 18, 533-543. Amandine Molliex : Presenilin function in the nervous system Aniko Nagy: IP3 signalling in development Cyclin B1-Cdk1 activity measured in a human cell progressing through mitosis. High activity correlates with a high FRET ratio. The measured values are plotted below the images over time. The stages of mitosis shown are: prophase; prometaphase (prometa); metaphase (meta); anaphase (ana. onset). NEBD = nuclear envelope breakdown.
Page 1 and 2: Department of Zoology Annual Report
Page 3 and 4: Malcolm Burrows FRS, Professor of Z
Page 5 and 6: Balfour & Newton Library The Balfou
Page 7 and 8: (a set of cards highlighting object
Page 9 and 10: Mathematical Biology (192 students)
Page 11 and 12: Manica, A, FK McMeechan & WA Foster
Page 13 and 14: Behaviour and Behavioural Neuroscie
Page 15: Mary Caswell Stoddard: Avian colour
Page 19 and 20: Tulay Atamert: Fly stocks maintenan
Page 21 and 22: Population and Community Ecology Ou
Page 23 and 24: Evolution and Diversity Much of the
Page 25 and 26: Awards and Prizes Michael Akam Linn
Page 27 and 28: Darwin’s ‘On the origin of spec
Page 29 and 30: Senior Assistant Curator of Malacol
Page 31 and 32: Krude, Dr T. Cancer Research UK, 20
Page 33 and 34: Champagne, F. A., Curley, J. P., Sw
Page 35 and 36: Harcourt, J. L., Ang, T. Z., Sweetm
Page 37: Stevens, M., Winney, I. S., Cantor,

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