Functional analysis of missense mutations in UNC13-D
Thursday 21 July 2011
Dr Peter van der Sluijs / Drs Edo Elstak
Project
Mutations in UNC13-D cause Familal Haemophagocytic Lymphohistiocytosis type 3 (FHL3). The autoimmune disease is characterized by haemophagocytosis, and the inability of cytotoxic lymphocytes to release their lytic granule contents and kill target cells. In this project we propose to characterize missense mutations of UNC13-D that have been found in FHL3 patients in UMC Utrecht. The approach will help to define the molecular requirents for munc13-4 in the degranulation pathway of cytotoxic lymphocytes.
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, 088 75 575 74