Casparian strips and suberin limit extracellular diffusion in plant roots by providing tight seals between adjacent cells, and between the cell wall and the plasma membrane, respectively. Such diffusional barriers are vital to enable the root endodermal cell layer to act as a selectivity barrier allowing controlled uptake of water and solutes into plants. Further, these barriers are also thought to provide a chemical or physical block to pathogen penetration into roots, including plant-parasitic nematodes accessing the vascular system for feeding. The molecular mechanisms that drive the biosynthesis of these critical barriers are poorly understood, limiting our ability to fully characterize their function and manipulate their properties for agricultural benefit. We have designed an ambitious interdisciplinary research programme integrating molecular plant science with analytical chemistry, whole plant physiology and modelling. This programme aims to deliver a complete understanding of the biology of Casparian strips and suberin, across scales, from molecules to the whole plant. Such information will enable a molecularly directed manipulation of Casparian strips and suberin, providing new pathways for the development of crop varieties with improved nutrient and water use efficiencies, and enhanced resistance to root pathogens, salinity and water stress. Such traits are essential if we are to develop crops that are more resilient to the predicted impacts of climate change on soil fertility, and to improve yields in a more sustainable manner to deliver the yield gains required to meet future population growth. By employing genomic, molecular genetic, chemical, biochemical and cell biological approaches we will discover and characterize the genes and molecular mechanisms involved in the biosynthesis of Casparian strips and suberin. Genetic resources characterized and developed through this mechanistic investigation will be leveraged to understand, at the root and whole plant level, the role of these physical and chemical barriers in mineral nutrient and water uptake, and root parasitic nematode infection. The ecological and adaptive function of these barriers to agriculturally relevant abiotic stresses such as water, mineral nutrient (deficiency and excess) and salinity will also be established. Building on this new understanding, mathematical models integrating molecular mechanistic knowledge with physiological processes at the tissue and whole plant level will also be built, providing predicative capacity to connect barrier properties with whole plant function.