Mitotic chromosome dynamics

Research

During cell division, the two copies of a cell's genetic material are completely separated and delivered to a pair of new daughter cells. Proper chromosome segregation requires the formation of correct attachments between the genetic material, assembled into chromosomes, and ends of microtubules. Our research is focussed on establishing the molecular mechanisms that mediate and monitor the correct attachment of chromosomes to microtubule at a special structure known as the kinetochore. To achieve this, we make use of advanced tools for imaging the components of cell division, especially in living cells and specialised mass spectrometry methods to probe the molecular machinery of cell division. Recently, we used these tools to discover a new protein, Bod1, that plays a critical role in the formation of correct attachments between microtubules and chromosomes by modulating the activity of Aurora B protein kinase. We recently installed a newly developed OMX microscope and are using this system to probe the inner workings of the centromere and kinetochore of the mitotic chromosome.

Teaching

Publications

Allan, C., Burel, J. M., Moore, J., Blackburn, C., Linkert, M., Loynton, S., Macdonald, D., Moore, W. J., Neves, C., Patterson, A., Porter, M., Tarkowska, A., Loranger, B., Avondo, J., Lagerstedt, I., Lianas, L., Leo, S., Hands, K., Hay, R. T., Patwardhan, A., Best, C., Kleywegt, G. J., Zanetti, G. and Swedlow, J. R. (2012) OME Remote Objects (OMERO): flexible, model-driven data management for experimental biology. Nat Methods. 9, 245-253, doi. 10.1038/nmeth.1896, PMID 22373911 View Paper

Posch M, Khoudoli GA, Swift S, King EM, DeLuca JG, Swedlow JR (2010) Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis. JCB. 191:61-74 PMID: 20921135 View Paper

Linkert M, Rueden CT, Allan C, Burel J-M, Moore W, Patterson A, Loranger B, Moore J, Neves C, MacDonald D, Tarkowska A, Sticco C, Hill E, Rossner M, Eliceiri KW, Swedlow J.R. (2010) Metadata matters: access to image data in the real world. 189: 777-782. PMID: 20513764 View Paper

Jaqaman K, King EM, Amaro AC, Winter JR, Dorn JF, Elliott HL, Mchedlishvili N, McClelland SE, Porter IM, Posch M, Toso A, Danuser G, McAinsh AD, Meraldi P, Swedlow J.R. (2010) Kinetochore alignment within the metaphase plate is regulated by centromere stiffness and microtubule depolymerases. J. Cell Biol. 188:681-692. PMID: 20212316 View Paper

Swedlow, J.R., Goldberg, I.G., Eliceiri, K.W., the OME Consortium (2009) Bioimage informatics for experimental biology. Annu Rev Biophys. 38:327-346. PMID: 19416072 View Paper

Khoudoli, G.A., Gillespie, P.J., Stewart, G., Andersen, J.S., Swedlow, J.R., and Blow, J.J. (2008) Temporal profiling of the chromatin proteome reveals system-wide responses to replication inhibition. Curr. Biol. 18:838-43. PMID: 18514518 View Paper

Murray, J.M., Appleton, P.L., Swedlow, J.R., and Waters, J.C. (2007) Evaluating Performance in three-dimensional fluorescence microscopy. J Microsc. 228(3):390-405. PMID: 18645334 View Paper

Porter, I.M., McClelland, S., Khoudoli, G.A., Hunter, C., Andersen, J., McAinsh, A.D., Blow, J.J., and Swedlow, J.R. (2007) Bod1, a novel kinetochore protein required for chromosome biorientation. J Cell Biol. 179(2):187-97. PMID: 17938248 View Paper

Wilcock, A.C., Swedlow, J.R., and Storey, K.G. (2007) Mitotic spindle orientation distinguishes stem cell and terminal modes of neuron production in the early spinal cord. Development 134:1943-1954. PMID: 17470968 View Paper

Goldberg, I.G., Allan, C., Burel, J-M., Creager, D., Falconi, A., Hochheiser, H.S., Johnston, J., Mellenm, J., Sorger, P.K., and Swedlow, J.R. (2005) The Open Microscopy Environment (OME) data model and XML File: open tools for informatics and quantitative analysis in biological Imaging.Genome Biol. 6:R47. PMID: 15892875 View Paper

Andrews, P.D., Ovechkina, Y., Morrice, N., Wagenbach, M., Duncan, K., Wordeman, L., and Swedlow, J.R. (2004) Aurora B regulates MCAK at the mitotic centromere. Dev Cell 6:253-268. PMID: 14960279 View Paper

Impact

• An Ocean of Images - Jason Swedlow at Cafe Science
• Spin-out Company: Glencoe Software