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31 يناير 2014
4 PhD student positions on ’Dynamics of coagulation Factor VIII von Willebrand factor and endothelial cells’ at Sanquin Research Amsterdam The Netherlands
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4 PhD student positions on 'Dynamics of coagulation Factor VIII von Willebrand factor and endothelial cells' at Sanquin Research Amsterdam The Netherlands
Are you a talented and highly motivated young scientist with a strong interest in pursuing a scientific career in cell biology or protein biochemistry? In that case you may feel challenged by one of these vacancies for PhD students in the field of thrombosis and hemostasis. In these positions you contribute to the research program of the Department of Plasma Proteins at Sanquin Research in Amsterdam. Sanquin has multiple academic affiliations which offer you the possibility of obtaining the PhD degree at one of the highranking universities in The Netherlands.
Regulation of WeibelPalade body exocytosis by syntaxin binding proteins 1 PhD student
You will be part of the team led by Dr. Ruben Bierings and Prof. Jan Voorberg which addresses the specialized secretory organelles called WeibelPalade bodies WPBs in vascular endothelial cells. Herein von Willebrand Factor is stored alongside a cocktail of hemostatic inflammatory and angiogenic mediators. Exocytosis of WPBs upon vascular perturbation allows the endothelium to actively participate in control of bleeding inflammatory responses and repair of the vessel wall. The molecular mechanisms that control exocytosis of WPBs are the subject of our current investigation see Bierings et al. Blood 2012 We have recently identified a new group of candidate regulators called syntaxin binding proteins STXBPs which we speculate to mediate docking and fusion of WPBs with the plasma membrane. This project will examine the role of STXBPs in WPB exocytosis through abination of cell biology and systems biology approaches including live cell imaging of WPB fusion and phosphoproteomics. Moreover we will study patients and individuals with inherited mutations or polymorphisms in these proteins as well as animal models of STXBP deficiency in order to determine the physiological relevance of STXBPmediated WPB exocytosis.Dynamics of Factor VIII and von Willebrand Factor 3 PhD students
You will join the team of prof. Koen Mertens and dr. Alexander B. Meijer. The first position focuses on the protein dynamics of Factor VIII. Despite the availability of crystal structures of Factor VIII we have limited understanding of the dynamics of Factor VIII assembly with its binding partners in a physiological context. While it is generally believed that the molecular architecture of theseplexes may differ significantly from that of the individual constituents the molecular changes that are driving these macromolecular interactions remain to be established. We are using recently developed innovative functional proteomics approaches such as chemical labeling using isobaric tandem mass tags TMTs to monitor the conformational dynamics in solution Bloem JBC 2013. Moreover hydrogendeuterium exchange HDX mass spectrometry will be used to monitor the dynamics of Factor VIII with its binding partners. The work of this PhD student will particularly focus on the procoagulant interactions of coagulation Factor VIII and engineered variants thereof.The other two positions focus on von Willebrand Factor vWF the natural carrier of Factor VIII in the circulation. vWF originates from endothelial cells where it is stored in WeibelPalade bodies in a condensed form. In response to blood flow and shear stress vWF can unfold into more stretched conformations that expose sites that support a variety of hemostatic networks. Apart from the chaperone role for Factor VIII these include the sheardependent uptake of vWF by macrophages Castro JTH 2012. In the present project we focus on the molecular interactions that drive interaction with cells that are capable of internalizing vWF and on the cellular receptors that mediate this process. One PhD student will address the vWF protein and the cellbinding regions therein while the other PhD student will investigate the membraneponents involved in the uptake mechanism of vWF. This project provides a novel stage in our longstanding research line on the relation between the LDLreceptor family and the clearance of Factor VIII and vWF Bovenschen Blood 2005. Our studies will take advantage of innovative mass spectrometry and footprinting approaches to identify the molecular interfaces involved in cellular uptake of vWF and of vWFFactor VIIIplex. We anticipate that such knowledge could lead to new therapeutic options for the treatment of hemophilia A.
About Sanquin and the Department of Plasma Proteins
Sanquin Blood Supply Foundation is an internationally acclaimed research institute that performs basic applied and clinically oriented research in the field of blood and blood transfusion. Our research focus includes thrombosis and hemostasis immunohematology and vascular biology. Research conducted at Sanquin aims to further our understanding of blood the interaction of blood with cells and genetic or acquired diseases affecting bloodponents in order to increase the safety or availability of blood products.Our team is embedded in the Department of Plasma Proteins where a vibrant international group of 2530 fellow colleagues group leaders postdocs PhD students and technicians is studying various aspects of hemostatic networks. To unravel critical interactions between hemostatic proteins and cells of the vasculature and the immune system we use a multidisciplinary approach that involves protein engineering molecular cell biology immunology and functional proteomics. The department's research program benefits from the excellent research facilities at Sanquin which include the newest technology for cell biology and biomolecular mass spectrometry. For more information see http://ift.tt/1iUQbid
Requirements
We are looking for highly motivated individuals who hold an MSc degree in biology biomolecular biomedical pharmaceutical sciences or equivalent. Candidates should have strong intellectual and experimental skills in addition to experience andor interest in cell biology protein engineering molecular biology live cell imaging andor systems biology. Preference will be given to candidates with international experience. Previous experience in working with animal models is a plus position 1.Benefits
Successful candidates will be offered a temporary fulltime position 36 hours for a period of 4 years with a salary starting from acirc130not2162 in the first year to acirc130not2770 in the forth year and travel expenses.More information
For further inquiries you can contact dr. Ruben Bierings position 1 at r.bieringssanquin.nl or prof. dr. Koen Mertens department head positions 24 at k.mertenssanquin.nl.Application
Please return your letter of application including a curriculum vitae and reference to application number MK 4613 preferably digitally via the online application form or via email t more...NT
via http://ift.tt/1fEUtoX