Molecular biotechnology

Organisation profile:Biological role of ECM1 in the human skin. The extracellular matrix proteine 1 gene (ECM1) was isolated in our laboratory in 1994 and encodes for a secreted glycoprotein with a typical cystein CC-(X7-10)-C pattern. Four splice variants have been described so far: Ecm1a (540 aa), Ecm1b (415 aa), Ecm1c (559 aa) and a truncated protein of 57 aa. Ecm1 has been shown to play a role in endochondral bone formation, morphogenesis of the nephron and is a stimulator of vascular endothelial cell growth in tumour stroma. In human skin ECM1 interacts with multiple proteins and proteoglycans (fibronectin, perlecan, laminin 332, collagen IV, fibulin-3, MMP-9) of the basement membrane and may act as a "biological glue" to maintain skin integrity and function. Furthermore,its importance in human skin is highlighted by the identification of loss-of-function mutations in ECM1 as the cause of the rare genodermatoses lipoid proteinosis (LiP) and auto-antibodies against ECM1 in lichen sclerosus, a chronic inflammatory disorder of the skin. However, the precise role of ECM1 in human skin is still unknown. Our research is focused on the physiological role of ECM1 in the skin and its relevance to epithelial-mesenchymal communication. Objectives: - To study the biological role of ECM1 using skin equivalent models - To determine the specific protein binding partners of ECM1 in human skin - To develop a mouse model for lipoid proteinosis - To study the photoprotective effect of ECM1 Methods: Basic molecular and cell-biological techniques (cloning, Southern-, Northern-,Western blot analysis, PCR- techniques ¿). Yeast two hybrid technology. In vitro transcription/translation and co-immunoprecipitation experiments. Functional analysis : RNAi technology in human primary keratinocytes and cell lines. Immunohistochemical analsis of human skin equivalents and mouse skin (after UV-irradiation and woundhealing).

Keywords:CHODL, ECM 1, C-TYPE LECTINS, SKIN BIOLOGY

Disciplines:Biochemistry and metabolism, Biomaterials engineering, Biological system engineering, Biomechanical engineering, Other (bio)medical engineering, Environmental engineering and biotechnology, Industrial biotechnology, Other biotechnology, bio-engineering and biosystem engineering, Medical biochemistry and metabolism