Busting blood clots
Blood is a very special and emotive fluid. If a blood clot would not form at the site of injury one could quickly lose a lot of blood. However, to this good side of blood clotting, there is also a bad side, i.e., it can happen inside intact vessels and prevent the free flow of blood. If this happens in important organs such as the heart or the brain then they stop functioning, and death results. Why does this happen and if it does happen, how can we reverse it? These are the questions we are interested in answering in our lab. With this research, we contribute to a better understanding of the mechanisms and treatment of diseases such as heart attack and stroke, which affects millions of people worldwide.
Introduction to the project and the overall aims:
Blood clotting is a complex interplay between many types of cells and blood proteins. We have focused our research on a protein called FSAP (Factor VII activating protease). This protein is interesting because a mutation, which inactivates the protein, is a risk factor for diseases such as stroke and thrombosis. We are performing molecular studies to understand how this protein works and how mutations influence the functions of the protein. We are identifying natural substrates for this protein. At another level, we are doing studies in cell culture to understand the effects of this protein on cells and to identify the receptors and signal transduction pathways involved. Last, but not least, we perform studies on mice where the gene for this protein has been inactivated to understand its functions at the level of the whole organism. Only by understanding all the details of the actions of FSAP can we identify new pathophysiological mechanisms and therapeutic targets for the treatment of thrombosis, stroke and heart attack. Thus, our research is multidisciplinary in nature.
Project goals and methods:
This project entails expressing FSAP and its mutants in bacteria and eukaryotic cells and studying its impact on cellular functions relating to signal transduction, cell survival and inflammatory mechanisms. The regulation of the activity of these enzymes will be studied using activators and inhibitors and classical enzymology. Techniques of molecular biology, cell biology and biochemistry will also be used in this project. Students will also learn about literature search, data analysis, written and oral presentation skills and issues related to publication. These very important skills can be translated across other disciplines and projects in the future. The project will be tailored to the interest/ inclination of the student as well as the state of the on-going projects in the lab at that particular time point.
I am the head of the “Vascular Pathophysiology Laboratory”, which is based in Domus Medica in the Institute of Basic Medical Sciences in the Faculty of Medicine. The composition of the lab varies with time and usually has postdoctoral fellows, PhD candidates and an engineer. The student will work either directly with me or with another postdoc / PhD student in the lab. In UiO, I have supervised three PhD candidates to completion and one PhD is currently submitted. I am also currently the co-supervisor for two PhD students and one Forskerlinje student.
Contact: if this project interests you, please come, meet us in the lab, and have an informal discussion about the possibilities of doing your project here.