The handle http://hdl.handle.net/1887/32636 holds various files of this Leiden University dissertation.
Author: Jongsma, Marlieke Lyrissa Maria
Title: A genome-wide cell biological analysis of genes involved in MHC class II antigen presentation
Issue Date: 2015-04-01
A genome-wide cell biological analysis of genes involved in MHC class II antigen presentation
Marlieke Lyrissa Maria Jongsma
The research described in this thesis was performed at the Division of Cell Biology II of the Netherlands Cancer Institute (NKI-AvL), Amsterdam, The Netherlands. Financial support was provided by Netherlands Organisation for Scientific Research (NWO) and European Research Counsil (ERC).
Financial support for printing of this thesis was provided by the Netherlands Cancer Institute (NKI-AvL).
A genome-wide cell biological analysis of genes involved in MHC class II antigen presentation
PROEFSCHRIFT ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op woensdag 1 april 2015
klokke 16.15 uur door
Marlieke Lyrissa Maria Jongsma geboren te ‘s-Gravenhage op 22 november 1984
Overige leden | Prof. dr. J. Borst (Universiteit van Amsterdam)
Prof. dr. S. M. van Ham (Universiteit van Amsterdam)
Prof. dr. F. Koning Prof. dr. A.J. Koster Prof. dr. A. Sonnenberg
Dr. R.M. Spaapen (Sanquin Research)
Table of contents
Prologue
Chapter 1 | Introduction: Towards a systems understanding of MHC class II antigen presentation
Nature Reviews Immunology, 2011 Nov 11;11(12):823-36 Chapter 2 | A genome-wide multidimentional RNAi screen reveals
pathways controlling MHC class II antigen presentation Cell, 2011 Apr 15;145(2):268-83
Chapter 3 | On the move: organelle dynamics during mitosis Trends in Cell Biology, 2015 (in press)
Chapter 4 | The E3-ligase RNF26 regulates Myosin VI mediated endosomal positioning in interphase and mitotic cells Chapter 5 | Identification of an E2 enzyme for the ER embedded E3
ligase RNF26
Chapter 6 | Summary & Discussion Nederlandse samenvatting
Curriculum vitae List of publications
7 11
27
69
95
131
145 153157 159
Prologue
The human genome comprises of more than 22.000 genes. These genes encode for proteins playing a role in many general or tissue-specific biological processes, but for many of them the function is not yet unraveled yet. A way to study all the different genes at once in a certain biological process is by genome-wide screening. By considering all genes in a pathway, new players can be identified that would otherwise not have been linked to the studied process.
In this thesis, I describe a siRNA-based genome-wide screen used to identify new proteins involved in MHC class II antigen presentation, expression and transport. The data obtained from this screen not only led to the identification of proteins involved in the MHC class II pathway specifically, but we also identified a regulator of a more general process namely intracellular endosome localization. This shows the importance of genome-wide screening in the identification of new players and regulators of certain biological pathways which may be considered as new drug targets to cure diseases.
