The position

As a PhD student at the section of Thrombosis and Hemostasis, you will examine structure-function relationships of serine proteases, a super family of enzymes that play an important role in blood coagulation. Molecular biology and biochemical techniques will be used to generate and characterize recombinant blood clotting proteins in vitro.

The project

The group of dr. Bos focuses on the engineering of novel, highly effective therapeutic proteins for the treatment of blood coagulation disorders, such as the bleeding disorder hemophilia, or, conversely, thrombosis.

Most of the enzymes that contribute to the formation of a blood clot are large complexes consisting of a serine protease and a cofactor. These enzymatic complexes assemble on a negatively charged membrane surface, such as that of platelets or endothelial cells, thereby directing these coagulation enzymes to the site of injury. Interestingly, several blood coagulation-like serine proteases are also expressed in the venom of various animals, such as snakes. These venom proteases are hallmarked by unique structural modifications, of which the functional consequences are largely unknown. To study this, the PhD student will generate a panel of recombinant protein variants using existing sequences and 3D-structural models of the venom proteases. If sequence information is lacking, these will be obtained employing next generation sequencing techniques. For the in vitro characterization of the recombinant protein variants, the PhD student will make use of enzyme kinetic analyses and other biochemical strategies. Specific protein variants will be assessed for their clotting efficacy in vivo employing established procedures.

We anticipate that a better understanding of the structure-function relationships of these unique venom proteases will provide us with essential information on the molecular mechanisms of the intricate coagulation system. This knowledge will contribute to the identification of novel targets and the development of modified therapeutic coagulation proteins with improved efficacy.

We are looking for a highly motivated individual with a recent Master’s degree in a biochemical, biomedical, or related field. Knowledge of or affinity with the biochemistry of proteins is desirable. You have a structured working style and are driven to find creative solutions to complex problems.

Candidates should have excellent written and verbal communication skills. Hands-on experience with molecular biology, protein chemistry, and next generation sequencing techniques in addition to a qualification in compliance with Article 9 of the Animal Experimentation Act is preferred.

Fixed-term contract: 4 years (duration of the degree).

You will be employed on the basis of a 36-hour week. The appointment is for the duration of the degree (four years). Your salary will depend on your qualifications and experience, with a maximum of € 2,279 gross per month in the first year, amounting to € 2,919 in the fourth year based on a full time position (scale PhD students, CLA UMC).

The terms of employment offered by the LUMC are highly favorable. For example, you will receive 8% holiday remuneration, a year-end bonus, and a pension arrangement with the National Civil Pension Fund. Also, as employee of one of the University Hospitals in the Netherlands, you can benefit from our collective health insurance policy.

Moreover, the LUMC offers excellent facilities in the area of education, child-care centers, and career advice. In addition, you may enjoy various leave arrangements and other extras. You can read more about these facilities elsewhere on this site.  

The LUMC is a center for medical innovation that aims to improve patient care through leading international research. So as to also provide our patients with a safe and friendly environment, we need doctors, medical care specialists, support staff and academic researchers. 

The research will be performed within an enthusiastic team of scientists at the section of Thrombosis and Hemostasis and the Einthoven Laboratory for Vascular and Regenerative Medicine at the Leiden University Medical Center. Research at the section of Thrombosis and Hemostasis focuses on the blood coagulation system, varying from in vitro and in vivo studies on the biochemical and cellular effects of specific coagulation proteins, to the discovery of environmental and genetic risk factors for venous thrombosis in patients, and development of novel treatment modalities for bleeding disorders. In the Einthoven Laboratory for Vascular and Regenerative Medicine, researchers from various disciplines (coagulation, cardiology, clinical epidemiology, endocrinology, nephrology, vascular surgery) perform a broad spectrum of studies with the overall goal of developing novel methodologies for the treatment of vascular- and coagulation-related diseases.