Signal transduction across cell membranes plays a central role in human physiology and disease, and nowhere is this more important than in the central nervous system. Receptors and transporters play critical roles in normal biology and in disease, and as a result these proteins have become preeminent therapeutic targets for drug discovery. Despite this, most membrane receptors and transporters remain incompletely understood.

The Kruse lab aims to address this challenge through structural and mechanistic studies of membrane proteins, as well as through the development of new technologies to understand membrane protein function. A recent focus of my group’s work is the sigma receptors, which are enigmatic membrane proteins linked to neurodegenerative and psychiatric diseases.  Using X-ray crystallography, we solved the structure of the human sigma-1 receptor, revealing how disease-associated mutations could affect its folding and function. In addition, we used classical biochemical approaches to determine the molecular identity of the sigma-2 receptor, which may be a useful therapeutic target but which has been challenging to study until now because the identity of the gene encoding it was unknown. In the long term, we aim to leverage a detailed molecular understanding of these and other receptors to facilitate the development of new and better therapeutics.