Young Lab

Conformational Dynamics in Signalling Proteins

Many proteins undergo changes in three-dimensional structure (conformation). My primary research interest is in understanding why and how this happens.

For instance, what makes one structure stable, and another unstable? Why do some conformational changes happen rapidly and others slowly? How can a particular conformation be stabilized by another associated molecule? These biophysical questions take on physiological significance in signal transduction, which relies on receptors that switch between inactive and active conformations in response to the binding of messenger ligands.

Almost every cellular process is regulated by signaling receptors, so new ligands designed to enhance or suppress the activity of specific receptors would be valuable drugs for treating many medical disorders. I hope to elucidate fundamental structural and energetic principles of receptor switching, so that the design of receptor-targeted drugs might one day become reliable and efficient.

One group of receptors that I am currently studying are ion channels which respond to the direct binding of the pivotal cytoplasmic messengers, cAMP and cGMP. These receptors thus link the well-known cyclic nucleotide signaling pathways to the electrical properties of the cell membrane. The electrophysiological technique of the membrane patch-clamp provides a powerful functional assay, sensitive enough in some cases to observe the activation of channels directly at the single-molecule level. My research program uses techniques from biochemistry and physiology in several investigations of ligand-activation mechanism.

Another branch of my team is studying light-receptors, in particular a diverse family of proteins which respond to ultraviolet radiation. One example is the enzyme photolyase found in bacteria: it exploits the light energy to repair genetic damage (DNA lesions) previously caused by radiation. This life-saving DNA repair capability depends on multiple features of protein structure such as specialized non-protein molecules (co-factors). We are testing the proposal that the difference between efficient and inefficient repair can hinge on the precise control of movements in the structure around the site that recognizes DNA.

More details on Ongoing Research Projects here. 



Lab Room:

SSB 7159

Lab Phone: 

(778) 782-5645

Office Room:

SSB 7155

Office Phone: 

(778) 782-4751


Technical Links for Young Lab members (password access): 
Technical Webpage   |   Sakai 

Selected Publications

  • Page et al. Cytoplasmic autoinhibition in HCN channels is regulated by the transmembrane region J. Membr. Biol. 2020
  • Magee et al. HCN channel C-terminal region speeds activation rates independently of autoinhibition. J. Membr. Biol. 2015
  • Wong et al. Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide-gated channels. J. Gen. Physiol. 2011
  • Wicks et al. Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating. Proc. Natl. Acad. Sci. USA 2011

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