Bowman Lab
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Research SummaryMy main interest is focused on how eukaryotic DNA is packaged and organised within the cell. In particular, I am interested in how the core histones are assembled into nucleosomes to create a platform for higher order chromatin structure. As many nuclear processes require access to the genome to exert their function, such as transcription, DNA replication & DNA repair, correct assembly and disassembly of chromatin structure is imperative for proper cellular function. Key to the chromatin assembly process is a set of histone specific chaperoning proteins that govern histone folding, storage and incorporation into chromatin. These are very dynamic processes, with histones being incorporated into chromatin within minutes of being synthesised in the cytoplasm. During this time it is thought that histones are transferred between a number of different chaperoning and histone modifying proteins in a maturation process that produces deposition-competent histones. I am interested in observing such transitions in living cells using the core histone H3 and H4 as models for chromatin assembly. In order to visualise and quantify such dynamic behavior in living cells I am developing a number of different methods that interface synthetic biology and protein engineering tools with state of the art live cell imaging approaches. It is hoped that being able to visualise these processes in real-time will broaden our understanding of one of the most fundament processes in chromatin biology. |
Selected PublicationsBowman A, Lercher L, Singh HR, Zinne D, Timinszky G, Carlomagno T3 Ladurner AG. (2015) "The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats." pii: gkv1372 PubMed Bowman, A., C. M. Hammond, A. Stirling, R. Ward, W. Shang, H. El-Mkami, D. A. Robinson, D. I. Svergun, D. G. Norman and T. Owen-Hughes (2014). "The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in solution." Nucleic Acids Res 42(9): 6038-6051. Hondele, M., T. Stuwe, M. Hassler, F. Halbach, A. Bowman, E. T. Zhang, B. Nijmeijer, C. Kotthoff, V. Rybin, S. Amlacher, E. Hurt and A. G. Ladurner (2013). "Structural basis of histone H2A-H2B recognition by the essential chaperone FACT." Nature 499(7456): 111-114. Bowman, A., R. Ward, N. Wiechens, V. Singh, H. El-Mkami, D. G. Norman and T. Owen-Hughes (2011). "The histone chaperones Nap1 and Vps75 bind histones H3 and H4 in a tetrameric conformation." Mol Cell 41(4): 398-408. Bowman, A. and T. Owen-Hughes (2012). "Sulfyhydryl-reactive site-directed cross-linking as a method for probing the tetrameric structure of histones H3 and H4." Methods Mol Biol 833: 373-387. Bowman, A., R. Ward, H. El-Mkami, T. Owen-Hughes and D. G. Norman (2010). "Probing the (H3-H4)2 histone tetramer structure using pulsed EPR spectroscopy combined with site-directed spin labelling." Nucleic Acids Res 38(2): 695-707. |
Lab Members and Projects
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Michael Smith | Research Associate I am using fluorescent microscopy to look at the histone chaperoning pathway in situ. My main goal is to delineate histone hand-off events that occur during histone chaperoning, but are difficult to observe with traditional biochemical approaches. |
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Elodie Debray | Undergraduate Project Student I am an undergraduate student from the University of Angers, France. My project is based on developing imaging methods to determine the location and timing of histone acetylation within the chromatin assembly pathway. |