Control of Cell Shape and Function
Our aim is to understand how cells control shape and size in relation to function.
Group head: Niels Galjart
Cells come in a variety of shapes and sizes, that are often intimately related to cell function. How do cells keep up their shape and size? How do they adapt, for example during migration or neuronal outgrowth? How are organelles and other cellular structures organized and maintained? Both the microtubule cytoskeleton and the nucleus are involved in maintaining cell shape, size and function. Research in my group focusses on critical proteins that control behaviour of the microtubule cytoskeleton (1) and that determine nuclear structure and output (2).
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| Intracellular fireworks. The microtubule plus-end tracking protein EB3 was tagged with GFP and transiently expressed in COS-1 cells. Using a confocal microscope images were acquired of a transfected cell. The time lapse movie shown here was accelerated 25 times.Comet-like dashes of EB3-GFP are seen moving through the cell. This is because EB3-GFP specifically associates with the ends of growing microtubules. | Zinc finger protein (ZFP) at work. Seminiferous tubules were dissected from the testis of a GFP-ZFP knock in mouse and, together with the DNA stain Hoechst, visualized under a confocal microscope. Shown is an image from part of the testis tubule. Notice how the GFP-ZFP localizes in the nucleus of all cell types in the testis, except spermatids, which are intensely stained by Hoechst |
Ph. D. Position Available: we are looking for a talented and motivated Ph. D. student with interest in the field of neuronal microtubules (see below for a more extensive explanation).
Microtubules and Microtubule Associated Proteins
Group members (1): Jeffrey van Haren (Ph. D. student), Ana Pereira (Ph. D. student), Soraya Verstraeten.
Microtubules are highly dynamic cytoskeletal elements, required for a variety of cellular functions. A family of microtubule plus end tracking proteins (+TIPs) was identified, that specifically associates with the ends of microtubules in different cell types. We are interested in determining the mechanistic roles that these proteins play in the regulation of microtubule dynamics. We initially concentrated on cytoplasmic linker proteins (CLIPs) and the CLIP-associated proteins (CLASPs). However, we have recently started to examine other +TIPs as well.
Ph. D. Position Available: A properly organized microtubule network is particularly important for neurons. Neuronal migration, for example, critically depends on forces exerted on the microtubule network. In addition, these cells are very long and the only efficient means for cellular constituents to reach neuronal extremities is by microtubule-based transport. Both developmental and neurodegenerative disorders of the human CNS have been linked to a dysfunctioning microtubule cytoskeleton. An optimal understanding of the molecular mechanisms involved requires fundamental knowledge of neuronal microtubules. We are looking for a talented and motivated Ph. D. student who is interested in further exploring the field of neuronal microtubules and microtubule dynamics. We will use live cell imaging in combination with biochemistry and cell biology to examine how the microtubule network is organized and maintained in neurons. We are particularly interested in analyzing the role of the CLIPs in this process. Interested candidates, who believe they fullfill our criteria, are welcome to submit an application to Niels Galjart (e-mail address).
Five recent publications in the filed of “Microtubules and Microtubule Associated Proteins”:
Akhmanova, A., Mausset-Bonnefont, A.L., van Cappellen, W., Keijzer, N., Hoogenraad, C.C., Stepanova, T., Drabek, K., van der Wees, J., Mommaas, M., Onderwater, J., van der Meulen, H., Tanenbaum, M.E., Medema, R.H., Hoogerbrugge, J., Vreeburg, J., Uringa, E.J., Grootegoed, J.A., Grosveld, F., and Galjart, N. 2005. The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis. Genes Dev 19(20): 2501-2515.
Drabek, K., van Ham, M., Stepanova, T., Draegestein, K., van Horssen, R., Sayas, C.L., Akhmanova, A., Ten Hagen, T., Smits, R., Fodde, R., Grosveld, F., and Galjart, N. 2006. Role of CLASP2 in Microtubule Stabilization and the Regulation of Persistent Motility. Curr Biol 16(22): 2259-2264.
Dragestein, K.A., van Cappellen, W.A., van Haren, J., Tsibidis, G.D., Akhmanova, A., Knoch, T.A., Grosveld, F., and Galjart, N. 2008. Dynamic behavior of GFP-CLIP-170 reveals fast protein turnover on microtubule plus ends. J Cell Biol 180(4): 729-737.
Galjart, N. 2005. CLIPs and CLASPs and cellular dynamics. Nat Rev Mol Cell Biol 6(6): 487-498.
Tanenbaum, M.E., Macůrek, L., Galjart, N., and Medema, R.H. 2008. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. Embo J in press.
Chromatin Organisation
Group members: Frank Sleutels (postdoc), Michael van der Reijden (technician), Widia Soochit (Master’s student), Lisa Caesar (Master’s student).
It is generally accepted that the architectural organisation of the nucleus and regulation of transcription are functionally linked, but how this occurs precisely remains to be determined. We are interested in describing the constituents of nuclear and nucleolar chromatin. We focus on the related, multi-zinc finger transcription factors CTCF and CTCF-L, which have been implicated in chromatin organisation and in the phenomenon of imprinting.
Five recent publications in the field of “ Chromatin Organisation”:
Burke, L.J., Zhang, R., Bartkuhn, M., Tiwari, V.K., Tavoosidana, G., Kurukuti, S., Weth, C., Leers, J., Galjart, N., Ohlsson, R., and Renkawitz, R. 2005. CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin. Embo J 24(18): 3291-3300.
Splinter, E., Heath, H., Kooren, J., Palstra, R.J., Klous, P., Grosveld, F., Galjart, N., and de Laat, W. 2006. CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev 20(17): 2349-2354.
Wesoly, J., Agarwal, S., Sigurdsson, S., Bussen, W., Van Komen, S., Qin, J., van Steeg, H., van Benthem, J., Wassenaar, E., Baarends, W.M., Ghazvini, M., Tafel, A.A., Heath, H., Galjart, N., Essers, J., Grootegoed, J.A., Arnheim, N., Bezzubova, O., Buerstedde, J.M., Sung, P., and Kanaar, R. 2006. Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol 26(3): 976-989.
Heath, H., de Almeida, C.R., Sleutels, F., Dingjan, G., van de Nobelen, S., Jonkers, I., Ling, K.W., Gribnau, J., Renkawitz, R., Grosveld, F., Hendriks, R.W., and Galjart, N. 2008. CTCF regulates cell cycle progression of alphabeta T cells in the thymus. Embo J 27(21): 2839-2850.
Ribeiro de Almeida, C., Heath, H., Krpic, S., Dingjan, G., Van Hamburg, J.P., Bergen, I., Van de Nobelen, S., Sleutels, F., Grosveld, F., Galjart, N., and Hendriks, R.W. 2009. Critical role for the transcription regulator CTCF in the control of T helper-2 cytokine expression. Journal of Immunology in press.