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Mechanisms of centrosome-mediated polarized CTL degranulation

Thursday 22 January 2009

Dr. Peter van der Sluijs / Drs Edo Elstak

Project
CTLs that encounter a target cell undergo a series of precisely orchestrated architectural changes that ultimately lead to release of granule contents at the immune synapse and subsequent killing of virally infected or transformed cells. It was recently shown that the microtubule organizing center (MTOC) moves the secretory granules to the immune synapse and docks them on the plasma membrane in a process that appears to be related to the formation of cilia. The molecular mechanism that is responsible for centrosome-mediated polarization of the secretory apparatus is not known. We recently identified p50, a novel centrosomal protein in haematopoietic cells and found that it interacts with proteins involved in degranulation. In this project we will define the mechanism how p50 functions in this novel polarization process.

Techniques
Molecular biology methods, lentiviral transduction, proteomics, advanced fluorescence techniques including live cell imaging, TIRF microscopy and FACS analysis.

Duration
6 or 9 months

References
Elstak ED, Te Loo M, Tesselaar K, van Kerkhof P, Loeffen J, Grivas D, Hennekam E, Boelens JJ, Hoogerbrugge PM, van der Sluijs P, van Gijn ME, van de Corput L. Pediatr Blood Cancer. 2011 Jul 13. doi: 10.1002/pbc.23253. [Epub ahead of print]

Elstak ED, Neeft M, Nehme NT, Voortman J, Cheung M, Goodarzifard M, Gerritsen HC, van Bergen En Henegouwen PM, Callebaut I, de Saint Basile G, van der Sluijs P. Blood. 2011 Jun 21. [Epub ahead of print]

Elstak E, de Jong A, van der Sluijs P. J Immunol Methods. 2011 Feb 28;365(1-2):58-66.

Neeft M, Wieffer M, de Jong AS, Negroiu G, Metz CH, van Loon A, Griffith J, Krijgsveld J, Wulffraat N, Koch H, Heck AJ, Brose N, Kleijmeer M, van der Sluijs P. Mol Biol Cell. 2005 Feb;16(2):731-41.

Contact
Dr. Peter van der Sluijs, p.vandersluijs@umcutrecht.nl, tel. 088 75 575 78

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