Cel Stem cells fascinate us from their defining characteristics; extensive proliferative potential and an ability to give rise to one or more differentiated cell types. The mechanisms that stem cells use to accomplish self-renewal promise fundamental insight into the origin and design of tissues. The Host laboratory is working for a long time on a very powerful model that is epidermis. The epidermis is a multilayered epithelium, which is punctuated by hair follicles and glandular structures. In human interfollicular epidermis, there are discrete clusters of stem cells; their transit amplifying progeny are proposed to migrate along the basement membrane away from the stem cell compartment. Stem cells are located in a specific microenvironment called a niche that is thought to be responsible for maintaining their selves properties. One element of the stem cell niche is likely to be the extracellular matrix. There is a growing body of evidence for heterogeneity in the composition of the basement membrane underlying the epidermis. We will test the hypothesis that local variation in the composition of the basement membrane could thus play a role in establishing and maintaining the distribution and properties of stem cells. In the first part of the project, I will document the composition of the ECM underlying epidermal stem cell clusters. Then, I will check the role of specific regions of the basement membrane in selectively anchoring stem cells. Finally, I will investigate whether the profile of ECM proteins produced by epidermal stem cells and their differentiated daughters differ. First, I will benefit from the facilities in the Cancer Research UK institute as well as the strong technical background of the Host laboratory. This project will allow me to expand my knowledge by discovering a physiological model the epidermis and to develop my technical expertise in the field of cell biology. To investigate the involvement of the components of basement membrane in the stem cells maintain, I will use both cell biology (primary cultures, transgenic mice, retroviral infection, Histological staining, confocal microscopy) and biochemical techniques as FACS sorting, northern blotting. Second, a position in the lab of Dr WATT lab would allow me to broaden my knowledge and acquire a high level of expertise in the mechanisms of keratinocyte differentiation. The Host laboratory will benefit from my technical experience in the field of signal transduction and microscopy. Finally, the proposed project will give us an insight into components of the epidermal stem cell niche leading to envisage new therapeutic strategy. Dziedzina nauki natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural sciencesphysical sciencesopticsmicroscopyconfocal microscopy Program(-y) FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002) Temat(-y) Data not available Zaproszenie do składania wniosków Data not available System finansowania RGI - Research grants (individual fellowships) Koordynator CANCER RESEARCH UK Wkład UE Brak danych Adres Lincolns Inn Field 44 WC2A 3PX LONDON Zjednoczone Królestwo Zobacz na mapie Koszt całkowity Brak danych
