Project 467231

Preterm birth is the world's leading cause of death for children under the age of 5. Yet, there are no effective medications to safely prevent this condition. Prostaglandin F2alpha (PGF2alpha) is a bioactive lipid that plays a role in several physiological functions, including the initiation of contractions during preterm birth. To act, PGF2alpha binds and activates a G protein-coupled receptor (GPCR) named FP on the cell surface. As such, FP is a promising therapeutic target for the prevention of preterm birth. GPCRs are good therapeutic targets, but the use of drugs aiming them is often accompanied by adverse effects. Recent advances in understanding the three-dimensional structure of these receptors have led to advances in the creation of drugs with fewer side effects. We want to use this new approach to study the structure of the FP receptor and to further investigate how it transmits the physiological signal of PGF2alpha, especially during the initiation of contractions in pregnant women. As such, we want to understand which elements are important so that the future drugs prevent preterm birth with minimum adverse effects. To do this, we propose to determine the general structure of the FP, how PGF2alpha binds to the receptor, and to identify the elements of the receptor responsible for the transmission of different cellular signals. With this information, we could develop tools to identify which signals from the FP are involved in the induction of contractions. In the long term, our work could lead to the elaboration of new strategies in the development of drugs for the prevention of preterm delivery.