Research Group KLUMPERMAN

Faculty of Medicine, UMC Utrecht, Department of Cell Biology
Contact: Dr. Catherine Rabouille
E-mail: j.klumperman@umcutrecht.nl
Website: http://www.cellbiology-utrecht.nl/groups/klumperman/index.html

General research focus: Membrane traffic and fly development

The aim of our research is:

1) to elucidate the functional organization and biogenesis the early exocytic pathway using Drosophila S2 cells and
2) to understand the role of the exocytic pathway in Drosophila development.
This exocytic pathway is crucial for cell survival and communication and mutations in genes encoding its keys proteins leads to very severe diseases ranging from bone malformations, coagulo-pathy, lipid metabolism disorder, defects brain development etc.

For Aim 1, we use Drosophila for the power of its (reverse) genetics and the ease of RNAi depletion in S2 cells that we combine with cutting edge microscopy. We have identified important aspects of the organization of the exocytic pathway and have recently shown that the Golgi is a paired organelle held by F-actin (through WAVE), and is part of a G2/M checkpoint.
We also study one of the factors that is at the basis of the organization of the early exocytic pathway, Sec16. Furthermore, we have started a microscopy based genome wide RNAi screen in Drosophila S2 cells to identify signaling molecules that are localized to the exocytic pathway and modulate its activity in response to signaling (collaboration with Michael Boutros). Using the same type of approache, we have also identified novel structural components involved in the functional organization of the exocytic pathway (in progress).

For Aim 2, it has become clear that the exocytic pathway (and more generally membrane traffic) can be acutely and specifically activated at certain stages of development. We have mostly focused on the fly oogenesis because it is the phase during which the body axes of the future individual are established by the deposition of known factors, such as Gurken, Oskar, and Bicoid (proteins and mRNAs).
In collaboration with Ilan Davis (Oxford, UK), we have studied the relationship between the exocytic pathway and the TGF alpha homologue Gurken as well as its mRNA, [ms under revision]. On the other hand, together with the group of Anne Ephrussi (EMBL, Heidelberg), we have shown that Oskar protein unexpectedly is a novel regulator of endocytosis in the oocyte and that contribute to the establishment of the polarity. Finally, we also study the role of the integrity of the follicular epithelium covering the oocyte in its development 2) We do all this by a combination of microscopy (including immuno-electron microscopy) for protein and RNA localisation, genetics, molecular biology and biochemistry, hard work but also a lot of good fun. We are always looking for enthusiastic and motivated Master students who are interested in cell biology or in bridging cell and developmental biology.

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