We propose to continue the COBRE on Membrane Protein Production and Characterization at the University of Delaware as a Phase III COBRE infrastructure center. The critical role of membrane proteins in biology is clearly reflected in the fact that they represent >30% of the human genome and are the targets of >50% of all therapeutics on the market today. Nevertheless, significant challenges remain in producing and characterizing them, especially within the realm of structural biology. Consequently the objectives of research in the COBRE will be to express, solubilize, purify and crystallize membrane proteins; to determine their structures; and to characterize their functions at the molecular level and in larger biological systems in both health and disease. These objectives are congruent with those of the Structural Biology component of the NIH Roadmap and the Protein Structure Initiative in addressing an area of critical importance for biomedical research. The infrastructure center will complement research in the laboratories of an interdisciplinary group of more than a dozen PIs, whose work is independently supported. To this end the center will include: research and instrumentation cores (Protein Expression and Biophysical Characterization; Structural Biology; and a group of Core Facilities co-funded with, among others, the Delaware INBRE); continuation of the current pilot research subproject program; a predoctoral training program modeled on the NIH T32 mechanism; and continuation of the existing annual symposium series. The administration of the center will be guided by an internal Steering Committee and will continue to benefit from the input of an External Advisory Committee, including for review of pilot project proposals. The research within the COBRE coupled with the capabilities provided by the infrastructure center will continue to give the University of Delaware distinctive strength in an area of research critical to biology and biomedicine.

Membrane proteins exist in the membrane surrounding each cell and are critical to cellular growth, communication and nutrition, yet how these proteins function is still relatively poorly understood. The purpose of this center is to provide infrastructure for research to develop improved methods to produce and study membrane proteins, which can yield major benefits for basic biology and drug development.