Research

Nanobodies and protein engineering

Antibody fragments are transformative tools in structural biology and pharmacology. In collaboration with the Manglik Lab (UCSF) we have developed a new platform for rapid and low cost discovery of single-domain camelid antibody fragments ("nanobodies"). Using this approach, we have discovered dozens of conformationally selective nanobodies targeting membrane proteins, enabling studies that wouldn't be possible otherwise. With an average turnaround time of three to four weeks, nanobody discovery in vitro is far faster and cheaper than animal immunization. Libraries and protocols are available upon request.

 

G protein-coupled receptors

G protein-coupled receptors (GPCRs) are cell-surface receptors that regulate neurotransmission, cardiovascular function, metabolic homeostasis, and many other processes. Due to their central role in human physiology, these receptors are among the most important targets of therapeutic drugs. To better understand GPCR signal transduction at a molecular level, we are using structural biology techniques including lipidic cubic phase (LCP) crystallography and other biophysical methods to study GPCRs with important roles in human health.

Other signaling pathways

In addition to work on GPCRs, we are also interested in signal transduction pathways that remain less extensively studied. These include the enigmatic sigma-1 and sigma-2 receptors, which we are investigating through X-ray crystallography and chemical biology methods. We are also investigating other important receptors with poorly defined signaling biology, particularly those involved in regulation of neurotransmission and metabolic disease.