Oliver P. Ernst

Oliver P. Ernst

Professor

Address MSB, Room 5219A
1 King's College Circle
Toronto, ON M5S 1A8
Lab Ernst Lab
Lab Phone 416-978-3852
Office Phone 416-978-3849
Email oliver.ernst@utoronto.ca

Research Description

Transmembrane Signaling by GPCRs and Channelrhodopsins

Cell membranes are natural borders for signal transduction between cells and their environment. Different strategies to enable signals to cross the membrane barrier employ protein classes such as G protein-coupled receptors (GPCRs), ion channels, and transporters. Our research is directed at understanding transmembrane signaling by GPCRs. We investigate the inner workings of these proteins and their interaction with signaling proteins like G proteins and arrestins. Using cryo-EM, x-ray crystallography, and various spectroscopic techniques, including electron paramagnetic resonance (EPR), we aim to gain insight into the mechanism, specificity, and structural basis of these interactions. A focus of our work is on rhodopsin, a GPCR model system and the photoreceptor protein in the vertebrate retina. Understanding how GPCRs work on a molecular level will help us to comprehend their role in health and disease.

Channelrhodopsins are microbial rhodopsins that act as light-gated ion channels and are used for optogenetic activation or silencing of mammalian neurons. Using cryo-EM, we study their mechanism of channel gating and ion selectivity. Other microbial rhodopsins work as ion pumps, which we also study by x-ray crystallography and EPR.

Additionally, we are interested in the localization of proteasomes, their structure and function in response to metabolic changes, and their potential role in liquid-liquid phase separation.

Awards & Distinctions

2011-2017 — Canada Excellence Research Chair in Structural Neurobiology
2011-2021 — Anne and Max Tanenbaum Chair in Neuroscience at University of Toronto
2020 — Konrad Adenauer Research Award (Humboldt Research Award Programme)

Courses Taught

Membrane Proteomics in Biomedical Research MMG 1313H
BCH374Y1 Research Project in Biochemistry
BCH473Y Advanced Research Project in Biochemistry
BCH422H Membrane Proteins: Structure and Function

Publications

View all publications on PubMed

Structural insights into light-gating of potassium-selective channelrhodopsin.
Morizumi et al.
Nature Communications (2025) 1283.  Read

Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities.
Morizumi et al.
Nature Communications (2023) 4365.  Read

Low pH structure of heliorhodopsin reveals chloride binding site and intramolecular signaling pathway.
Besaw et al.
Scientific Reports (2022) 12:13955.  Read

Serial femtosecond and serial synchrotron crystallography can yield data of equivalent quality: A systematic comparison.
Mehrabi et al.
Science Advances (2021) 7:eabf1380  Read

High-throughput in situ X-ray screening of and data collection from protein crystals at room temperature and under cryogenic conditions
Broecker et al.
Nature Protocols (2018) 13:260-92.  Read

Cryo-EM structure of the native rhodopsin dimer in nanodiscs
Zhao et al.
JBC (2019) 294:14215-14230  Read

Cryo-EM structure of human rhodopsin bound to an inhibitory G protein
Kang et al.
Nature (2018) 558:553-558  Read

Electron paramagnetic resonance spectroscopy on G-protein-coupled receptors: Adopting strategies from related model systems.
Reichenwallner et al.
Current Opinion in Structural Biology (2021) 69:177-186.  Read

Stationary Phase EPR Spectroscopy for Monitoring Membrane Protein Refolding by Conformational Response.
Balo et al.
Analytical Chemistry (2019) 91:1071-1079.  Read

Proteasome dynamics in response to metabolic changes.
Enenkel C & Ernst OP.
Frontiers in Cell and Developmental Biology (2025) 13:1523382.  Read

Intracellular localization of the proteasome in response to stress conditions.
Enenkel C et al.
Journal of Biological Chemistry (2022) 298:102083.  Read

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates.
Hermet et al.
PLoS Pathogens (2023) 19:e1011532.  Read