The Interdisciplinary Basic Research in Dermatology Program has two fundamentally related goals: to expand the understanding of the structure, function and differentiation of normal skin, and to understand the molecular pathobiology of selected inherited disorders of the epidermis, dermis and dermal-epidermal junction. The five integrated projects and three Core facilities share strategies, reagents and personnel to pursue these objectives. The integrating theme of the projects is a molecular and genetic approach to understanding how skin is formed, how epidermis differentiates, and how mutations alter the processing of mRNA, protein interactions, and matrix formation. In Project 1 (Dale) the central questions concern the manner in which filaggrin contributes to terminal differentiation of epidermis, including cell death. In Project 2 (Stephens) the major themes concern the keratin filaments, how the component molecules interact with their partners and other cellular components, and the manner in which mutations in keratin genes alter interactions among these molecules to alter cell structure and influence epidermal differentiation. In Project 3 (Byers) the central questions concern how mutations in collagen genes alter mRNA processing and intracellular transport of molecules that contain the altered gene products. For Project 4 (Piepkorn) the central theme is the manner in which epidermal growth and differentiation are mediated by autocrine mechanisms, the factors involved in autocrine signaling, and how altered responses to these signals may induce aberrations in epidermal proliferation or differentiation. Finally, in Project 5 (Carter) the focus is on how hemidesmosomes and adhesion complexes function and transmit signals for homeostasis, growth, wound repair, and differentiation in response to the environment.