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Förslaget inkom 2003-12-04

Maturation of bloodvessels in vitro and in vivo

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
Introduction
The main focus of this group is to understand the biology of bloodvessels and their role in tumor formation and fibrosis. Fibrosis is a common denominator in a wide variety of diseases characterized by chronic inflammation including stroma formation in solid tumors, rheumatoid arthritis and inflammatory bowel disease, connective tissue diseases, atherosclerosis, heart failure, transplant rejection and wound healing to name a few. The progression of fibrosis in these diseases leads to the derangement of tissue architecture and subsequent failure of the organ. In many of these diseases current therapeutic approaches have only marginally contributed to cure and must be seen as approaches that delay the progression of the disease. However, in certain circumstances in the adult, diseased organs (for instance the kidney in glomeruloid nephritis, the liver after hepatitis, and the heart during ventricular hypertrophia) are capable of healing themselves with minimal damage to the tissue and its function. Tissue regeneration following damage to an organ during embryogenesis and infancy is also an example of tissue repair with minimal functional sequel. In the adult, a pregnant women together with the fetus is able to create a new functional organ, namely the placenta. Thus, the adult body has mechanisms by which to adequately repair damaged organs and even create new organs. Why the body does not always achieve this, and what causes progression in one instance, and healing in another, is largely unknown and is one of the main subjects of study in the lab.

Several lines of investigation are currently being set up in the lab to address different aspects of the process of bloodvessel formation, fibrosis and tissue regeneration involving; gene therapy; microarray techniques combined with proteonomics; isolation of stem cells and how they are able to differentiate into collagen type I producing fibroblasts in the body and in the culture dish; low molecular weight drug therapy; and isolation of novel substances which may inhibit the development of fibrosis and tumor progression.

Project
The third line of investigation is to study the maturation process of blood vessels. This study will include in vitro and in vivo techniques and focus on the angiopoietin/Tie system which is a growth factor family that is thought to play an important role in vessel destabilisation and maturation. Specific questions here regard cell-cell interactions and transfer of growth factors to their receptors, as well as developing in vitro screening models to study vessel maturation. Using an animal model for vessel maturation which has already been developed molecular mechanisms leading to stabilization and destabilisation of the vessel will be studied. Also known compounds as well as compounds which are being isolated in the lab will be used in this model to study their effects on vessel maturation.

This project is basically the following: Coculture experiments will be performed between endothelium and pericytes. Phosphorylation of important proteins will be studied using IP and western blotting procedures. In particular the angiopoietin/tie system will be studied to see if a potential ligand for tie-1 can be found. This will be complemented by in vivo studies using adenoviral gene constructs in order to extrapolate the in vitro information to in the in vivo situation

This project I think would interest scientists whom want to learn about cell biology, biochemical analysis on the protein level, cell isolation techniques, animal work, blood vessel formation, protein analysis, tissue processing, and tissue analysis.


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