Final Report Summary - EUREGENE (European renal genome project)
The ultimate aim of the EUREGENE project was to form an interdisciplinary research programme that integrated European excellence in research relevant to renal development, pathophysiology and genetics. The goal was to discover genes responsible for renal development and disease, their proteins and actions. To achieve this goal, a consortium of leading scientists, clinicians and Small and medium-sized enterprise (SME) partners that focus on the development of novel technologies and discovery tools in functional genomics and their application to kidney research was established.
EUREGENE had four specific objectives in scientific areas that were most relevant to functional genomic research in human kidney diseases, namely functional genomic technologies, renal development, pathophysiology, complex genetics
Functional genomic technologies
Methods for automated high throughput In situ hybridisation (ISH) on kidney sections and Optical projection tomography (OPT) were used to establish a Three-dimensional (3D) map of the embryonic and the adult kidney transcriptome in mice and Xenopus. All data produced would be incorporated in specific databases. Bioinformatic tools will be developed to link all EUREGENE databases and to establish a kidney atlas in which mechanisms of renal development and disease could be studied in a spatiotemporal framework.
Renal development
Developmentally expressed genes would be identified on a large scale using microarray and in situ hybridisation in cell lines, organ cultures and embryos, and their expression mapped back onto the developing kidney. Candidate genes would be followed up by gene targeting or transgenic studies, as well as cell lineage and organ culture studies would be performed to understand the origin of cellular components of the kidney. Furthermore, differentiation pathways from renal stem cells to components of the kidney would be explored and all data would be incorporated in a 3D atlas of the renal transcriptome.
Pathophysiology
Rat and mice models with perturbations in key renal genes would be established using knockout and transgene technologies. Special focus would be laid on genes associated with human renal disease and sophisticated methods for the characterisation of renal function in laboratory animals including morphological and pathophysiological tests, expression profiling, and imaging would be applied to define disease processes and to uncover novel regulatory networks in renal pathophysiology.
Complex genetics
Systematic random ENU mutagenesis approaches in zebrafishes and mice would be applied to generate new models of impaired renal development and function, which would be further characterised by pathophysiological and positional cloning approaches. Established rodent models of diabetic nephropathy, glomerulosclerosis, proteinuria and renal stone disease would be used to map modifier gene loci that affect disease progression and to identify new disease genes by linkage/positional cloning.
EUREGENE had four specific objectives in scientific areas that were most relevant to functional genomic research in human kidney diseases, namely functional genomic technologies, renal development, pathophysiology, complex genetics
Functional genomic technologies
Methods for automated high throughput In situ hybridisation (ISH) on kidney sections and Optical projection tomography (OPT) were used to establish a Three-dimensional (3D) map of the embryonic and the adult kidney transcriptome in mice and Xenopus. All data produced would be incorporated in specific databases. Bioinformatic tools will be developed to link all EUREGENE databases and to establish a kidney atlas in which mechanisms of renal development and disease could be studied in a spatiotemporal framework.
Renal development
Developmentally expressed genes would be identified on a large scale using microarray and in situ hybridisation in cell lines, organ cultures and embryos, and their expression mapped back onto the developing kidney. Candidate genes would be followed up by gene targeting or transgenic studies, as well as cell lineage and organ culture studies would be performed to understand the origin of cellular components of the kidney. Furthermore, differentiation pathways from renal stem cells to components of the kidney would be explored and all data would be incorporated in a 3D atlas of the renal transcriptome.
Pathophysiology
Rat and mice models with perturbations in key renal genes would be established using knockout and transgene technologies. Special focus would be laid on genes associated with human renal disease and sophisticated methods for the characterisation of renal function in laboratory animals including morphological and pathophysiological tests, expression profiling, and imaging would be applied to define disease processes and to uncover novel regulatory networks in renal pathophysiology.
Complex genetics
Systematic random ENU mutagenesis approaches in zebrafishes and mice would be applied to generate new models of impaired renal development and function, which would be further characterised by pathophysiological and positional cloning approaches. Established rodent models of diabetic nephropathy, glomerulosclerosis, proteinuria and renal stone disease would be used to map modifier gene loci that affect disease progression and to identify new disease genes by linkage/positional cloning.