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Institute of Interdisciplinary Research in human and molecular Biology
IRIBHM is part of the Medical School of the Univerité Libre de Bruxelles (ULB) and one of the largest research structures of the university. Founded in the nineteen sixties with the aim of applying an interdisciplinary approach to the study of thyroid pathophysiology, the Institute has thrived over the years into a number of independent groups with diversifying research interests. Presently, about 130 researchers and technicians are working in the Institute over a range of subjects encompassing signal transduction, development, neuroscience, and cancer, using cell and molecular biology approaches. Staff researchers include physicians, physicists, bioinformaticians, (bio)chemists and biologists. The activities of IRIBHM are mainly taking place on the Erasme campus of ULB, in the suburb of Brussels, although the Institute also contributes to the Institut de Biologie Moléculaire et Médicale (IBMM) on the Gosselies campus. The heavy equipment is common to the whole Institute and often shared with other groups of the campus as technical platforms. This includes genomics, proteomics, transgenesis, FACS and confocal microscopy facilities.
Molecular genetics of hereditary diseases
Interactions with the Medical Genetics department allow the ascertainment of families with rare hereditary diseases. Studies aim at localizing the gene in the genome by means of linkage analysis, or physical mapping of chromosomal deletions or translocation breakpoints when available. The genomic interval is then inspected for candidate genes, which in turn are studied for mutations in affected family members. Examples of such rares diseases are primary microcephaly and congenital corneal dystrophy. The linkage analysis and candidate gene approach is also applied to complex inherited disorders like congenital athyreosis and primary pulmonary hypertension.
G protein-coupled receptors (GPCRs)
After having pioneered the cloning by homology of rhodopsin-like GPCRs in the late eighties, the Institute has built expertise in the study of a variety of GPCR subfamilies. These include mainly the glycoprotein hormone receptors, receptors for chemokines and other leucocyte chemoattractants, adenosine receptors, P2Y nucleotide receptors, cannabinoid receptors. Studies include structure-function relationships (glycoprotein hormone receptors, chemokine receptors, purinergic receptors), regulation of downstream cascades and gene expression by microarrays (leucocyte receptors), in vivo phenotypic studies of mice with invalidated receptor genes (adenosine A2a receptor, cannabinoid CB1 receptor, prolactin-releasing peptide receptor, P2Y4, P2Y6 and P2Y13 receptors, orphan receptors). The group studies also GPCR dimerization and the pharmacological and functional consequences of this process. In addition, a strong emphasis is put on the identification of the natural agonists of a wide diversity of orphan GPCRs, and the functional characterization of these receptors in physiology, human diseases and animal models.
DNA microarray is a powerful technology that provides the expression profile of thousands of genes simultaneously. Applications to cancer biology and diagnosis include molecular tumor classification, drug sensitivity, or identification of tumor-specific molecular markers. In the field of drug discovery and development, it can help identifying appropriate targets for therapeutic intervention, as well as monitoring changes in gene expression in response to drug treatments. We have implemented this technology and are currently focused on gene expression profiling of thyroid tumors, and transcriptional regulation promoted by specific receptors in leucocytes.