The aim of the Research Unit is to obtain a detailed understanding of the biomolecule-controlled nano- and microscale processes that enable diatoms to produce their intricately patterned silica- based cell walls. In previous research the structures and properties of hydrophilic (“soluble”) diatom silica-associated biomolecules (long-chain polyamines and proteins termed silaffins and silacidins) have been extensively investigated. These pioneering studies have provided the first insights into the molecular mechanisms of biological silica formation. However, they identified only a small subset of the silica forming cellular machinery leaving an insurmountable gap in mechanistic understanding between the properties of the currently known silica forming biomolecules and the process of silica morphogenesis in vivo. Recently, diatom silica-associated organic matrices have been identified, that exhibit characteristic nanopatterns, and are insoluble in aqueous solution. Nanopatterned insoluble organic matrices are also present in other biominerals (e.g., sponge silica, mollusk calcite) suggesting a fundamental role in biological mineral morphogenesis. Based on this hypothesis our Research Unit proposes a novel approach to elucidate the chemical and physical principles that govern silica morphogenesis in diatoms. Utilizing state of the art biochemical, biophysical, and molecular genetic methods we aim to analyze the biomolecular composition and assembly of the insoluble organic matrices, study their interaction with the soluble silica-associated biomolecules, and characterize in unprecedented detail the structure of the bioorganic-inorganic interface. Like many other biomineralization processes biological silica formation takes place in intracellular lipid bilayer-bound compartments, called silica deposition vesicles (SDVs). However, the role of lipid bilayer-bound compartments in biomolecule-controlled silica morphogenesis has so far remained unexplored. We intend to address this question by investigating the influence of lipid bilayer- bound microcompartments on the self-assembly of the silica forming biomolecules, and on silica morphogenesis. Furthermore, we will attempt to isolate SDVs for the first time, and characterize their biochemical composition, which would reveal the entire biomolecular machinery directly involved in silica formation. By in vitro reconstitution of the silica forming machinery from synthetic molecules, and in combination with computational modeling we aim to obtain a detailed picture of the silica morphogenesis process from the sub-nanometer to the micrometer scale. Due to the already existing molecular data on diatom silica biomineralization, the plethora of available diatom genome sequence information, and the available tools for genetic manipulation of diatoms make this group of organisms - in our view - the best system for studying the molecular fundamentals of biological silica mineralization. We anticipate that the work of the Research Unit will not only elucidate generic molecular principles of biomineral morphogenesis, but also be relevant for other research fields including biomolecular self-organization, organic- inorganic hybrid materials synthesis, and nanomaterials science.