MEMPROT · The technologies of biological membranes

Final Activity Report Summary - MEMPROT (The Technologies of Biological Membranes)

This project was concerned with the establishment of a laboratory for the study of membrane proteins, a highly topical area of research which is particularly relevant to developing regions within the EU because it offers translational opportunities to the private sector viz. in the area of drug discovery, an activity which the Irish State is keen to encourage. The project was supported by a special University subvention which allowed the infrastructure of the laboratory to be established. The research strategy adopted was to develop membrane-related aspects of topics already under study in the University, coupled with the importation of new areas of research which had potential in the drug discovery area. Thus, research projects were conducted on G-protein coupled receptors (GPCRs) in the field of inflammation and immunity where new expression of both receptor and ligand were achieved. Such receptors command nearly a third of research investment in modern pharma. The very challenging barrier of eukaryotic protein expression was successfully tackled whereby tobacco plants were transformed with vectors containing a GPCR and a ligand-binding domain and seen to express protein. Again, heat shock proteins (yeast disaggregases) were shown to enhance the yield of soluble expressed mammalian proteins in E.coli. All these open up new prospects for circumventing this difficult barrier. The structure and function of a newly identified receptor, that for retinol binding protein, was initiated. A key domain of the protein was expressed and demonstrated to retain native functionality. This allowed a screening assay to be developed which in turn led to the discovery of two series of compounds which were shown to prevent the development of insulin resistance and type 2 diabetes in mice. These are now the subject of some interest by the private Pharmaceutical sector. A yeast-2-hybrid system for use with membrane proteins in order to identifying interacting components with signal tranduction potential was established and used to screen for interactors with this receptor. Finally, a difficult domain, mutations in which are responsible for some forms of retinitis pigmentosa was expressed and the mutations responsible shown to cause aggregation resulting in loss of function and consequent disease. An advanced course on the structure and function of membrane proteins was conducted and undergraduate research projects were designed and supervised by the Marie Curie Fellows. Following its inception, the Laboratory has attracted additional and new funding from a variety of sources as well as independent research Fellows which will ensure that the work initiated will continue and develop. The University has made an appointment in the area to ensure that the Laboratory has a long-term future as an established research unit. Thus, the objective of establishing membrane protein research at NUIM has been amply fulfilled.

Data: CORDIS, © European Union