Vacant positions / Ledige stillinger
Master project in cancer research
Monoclonal antibodies against the urokinase plasminogen activator (uPA): Characterisation and evaluation of functional inhibition
An attractive master project within cancer research and cancer therapy in mice is now available at Finsen Laboratory. We are looking for a highly motivated student in molecular biology, biomedicine, biochemistry, or human biology. The project will be carried out in the Høyer-Hansen research group at the Finsen Laboratory, which is located in Copenhagen Biocenter and is a part of Rigshospitalet. The common goal of our research is to reveal and test new drug targets for cancer therapy as well as to investigate the basic biological mechanism in cancer development and invasion. .
Start: As soon as possible
Duration: 12-24 months
Location: Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter
Project description
The enzymatic degradation of extracellular matrix proteins is a crucial event in malignant tumor growth and metastasis and is almost always the cause of a fatal course of cancer.
Tissue remodelling and cell migration are dependent on the confined degradation of proteins in the extracellular matrix and basement membranes, which is accomplished by the concerted action of several proteolytic enzymes, such as the protease urokinase-type plasminogen activator (uPA). uPA has been demonstrated to play a central role in tissue remodelling processes, both during normal physiological conditions such as wound healing and under pathological conditions such as cancer invasion and metastasis.
Most of our understanding of the role of uPA in vivo is derived from studies using gene-targeted uPA-deficient mice. To enable in vivo studies on the specific interference with uPA functionality in mouse models, monoclonal antibodies (mAbs) directed against mouse uPA and with inhibitory effect on the activity of mouse uPA are required. If successful, this strategy can be utilized in future development of anti-invasive therapy in cancer patients.
Project aim
By taking advantage of in-house developed monoclonal antibodies directed against mouse uPA, the aim is to determine the effect of these mAbs on the uPA functionality through thorough characterization and testing of the antibodies.
Methods
During the project the student will be trained in basic biochemical and biological methods, such as SDS-PAGE analysis, Western blotting, Surface Plasmon Resonance and enzyme kinetic analyses as well as production and purification of monoclonal antibodies and cell-based assays. Furthermore, the student will obtain experience in immunohistochemical staining procedures and basic animal handling.
The Finsen Laboratory
The Finsen Laboratory is a cancer research laboratory with main focus on experimental research within the field of cancer invasion and metastasis. The Finsen Laboratory has been engaged in protease research in relation to cancer for decades and possesses extensive experience in both in vitro and in vivo methods. The laboratory is situated in the Copenhagen Biocenter, which offers modern laboratory and animal facilities. The laboratory functions in 4 separate research groups, each headed by a research leader, but all in close collaboration. The personnel consist of 22 scientists and 11 laboratory technicians, a research coordinator, a photographer and a secretary.
The application
Please hand in your application by 1. March 2010. In addition to the application, CV and information on academic grades and courses should be included.
For more information please contact
Ida Katrine Lund
Finsen Laboratory
Copenhagen Biocenter
Ole Maaløes Vej 5, building 3.3
Phone: 35456028
Email: ikl(at)finsenlab.dk
References of relevance for the project:
I.K. Lund, A. Jögi, B. Rønø, M.G. Rasch, L.R. Lund, K. Almholt, H. Gårdsvoll, N. Behrendt, J. Rømer, and G. Høyer-Hansen. Antibody-mediated targeting of the uPA proteolytic function neutralizes fibrinolysis in vivo. J. Biol. Chem. 283 (47):32506-32515, 2008.
M.G. Rasch, J. Pass, M. Illemann, G. Høyer-Hansen, I.K. Lund. Discrimination of different forms of the murine urokinase receptor on the cell surface using monoclonal antibodies. J. Immunol. Methods. 339 (1):55-65, 2008.
J. Pass, A. Jögi, I.K. Lund, B. Rønø, M.G. Rasch, H. Gårdsvoll, L.R. Lund, M. Ploug, J. Rømer, K. Danø, G. Høyer-Hansen. Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: Inhibitory effects on receptor-mediated uPA activity in vitro and in vivo. Thromb. Haemost. 97 (6):1013-1022, 2007.
K. Almholt, L.R. Lund, J. Rygaard, B.S. Nielsen, K. Danø, J. Rømer, and M. Johnsen. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice. Int. J. Cancer 113 (4):525-532, 2005.
K. Danø, N. Behrendt, G. Høyer-Hansen, M. Johnsen, L.R. Lund, M. Ploug, and J. Rømer. Plasminogen activation and cancer. Thromb. Haemost. 93:676-681, 2005.
