Extracellular matrix macromolecules are often large oligomers that polymerize into supra-structures at several hierarchic levels. They form insoluble fibrils or filaments that further assemble into tissue supramolecular structures. These supra-structures can be visualized as building blocks for formation and homeostasis of tissues and organs. On one hand, such supra-structures often confer structural support to tissues, and on the other hand they have numerous functional roles in development and homeostasis of tissues and organs. Deficiencies in formation and/or function of such supra-structures can lead to numerous genetic and degenerative disorders, affecting essentially all organs and tissues. One subset of these supramolecular structures is represented by microfibrillar systems, which are ubiquitously distributed in most elastic and non-elastic tissues. The fibrillin family of proteins forms the core of these supra-structures. Mutations in individual components of these systems give rise to a broad spectrum of genetic disorders generally termed microfibrillopathies including the Marfan syndrome (fibrillin-1), contractural arachnodactyly (fibrillin-2) and related disorders characterized by clinical symptoms in the cardiovascular, skeletal, and ocular systems. In order to advance the understanding of genotype-phenotype relationships in such disorders, information about microfibrillar systems in terms of biogenesis and functional aspects is urgently needed. The research in Dr. Reinhardt’s group is driven by the "long term" hypothesis of the laboratory that microfibrillar systems are essential for biogenesis, homoeostasis, and degeneration processes of cardiovascular and skeletal tissues. Basically, the research projects address three important aspects of microfibril biology, which are (i) biogenesis of microfibrils, (ii) genotype-phenotype relationships of genetic disorders, and (iii) the ligand interaction repertoire and its functional significance. Dr. Reinhardt’s laboratory uses a combined biochemical, cell biological, genetic, proteomic and recombinant protein technology approach to identify the components and mechanisms involved in these basic pathways of microfibril biology in health and disease. It is expected that information obtained from this work will directly contribute to the design of diagnostic and therapeutic strategies for associated disorders.
Christine Fagotto-Kaufmann, Research technician
Dirk Hubmacher, Postdoctoral fellow
Melkamu Getie, Postdoctoral fellow
Yan Zhang, PhD student