Are you a talented and highly motivated young scientist with a strong interest in a scientific career in protein engineering and biochemistry? You then may feel challenged by one of our vacancies for a postdoc/PhD-student position in the field of thrombosis and hemostasis. This provides an opportunity to participate in the research program of the Department of Plasma Proteins at Sanquin Research in Amsterdam. Sanquin has academic affiliations with multiple high-ranking universities in The Netherlands.
Factor VIII is the cofactor for activated factor IX in the coagulation cascade. It is a large, multi-domain protein that comprises interactive sites for multiple binding partners, including its carrier von Willebrand factor, Factor X, activated Protein C, lipid membranes and endocytic receptors. Despite the availability of crystal structures of Factor VIII, we have limited understanding of the dynamics of Factor VIII assembly with its partners in a physiological context. While it is generally believed that the molecular architecture of these complexes 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 innovative functional proteomics techniques such as chemical labeling using isobaric tandem mass tags (TMTs) and hydrogen-deuterium exchange (HDX) mass spectrometry to monitor the conformational dynamics at the various domain interfaces (see Bloem et al, JBC 2013 288(41):29670-9 and 288(36):26105-11 and references therein). In a parallel approach, we will engineer Factor VIII in its interactive sites in order to increase its stability and biological activity, and to decrease its affinity for components involved in clearance from the circulation. For this purpose we will address domain swaps with other, structurally related proteins as well as more refined mutagenesis at the level of individual amino acids. We anticipate that such knowledge could lead to novel protein therapeutics for the treatment of hemophilia A.
Where you will work:
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 haemostasis, (immuno)hematology 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 blood components in order to increase the safety or availability of blood products.
Our team is embedded in the Department of Plasma Proteins, where an international group of 25-30 fellow colleagues (group leaders, postdocs, PhD students and technicians) is studying various aspects of haemostasis. To unravel critical interactions between hemostatic proteins and cells of the vasculature we use a multidisciplinary approach that involves protein engineering, molecular cell biology 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://www.sanquin.nl/en/research/departments/plasma-proteins/
We are looking for:
We are looking for highly motivated candidates who hold a MSc or PhD in Biomedical Sciences, Molecular Sciences, Biochemistry or a related field. Candidates should have strong intellectual and experimental skills, in addition to experience/interest in biomolecular design, HDX mass spectrometry, biochemistry, and fluorescent imaging techniques.
We offer you the following employee beneftis:
- salary and conditions are conform CAO Sanquin;
- a temporary appointment for a period of 4 years (PhD student) or 2-3 years (Postdoc);
- 8,33% year-end;by full-time employment (36 hours) 201 vacation hours;
- reimbursement of travel expenses;
- collection agreements with various insurers;
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