RESEARCH
Research in the Autzen Group is focused on understanding the molecular mechanisms involved in taste signaling and metabolic homeostasis, with a particular emphasis on developing new tools for detergent-free membrane protein purification.
EXPERIMENTAL APPROACHES
Our group utilizes mammalian expression systems for protein expression and production and employs single-particle cryo-EM in combination with biochemical, biophysical and pharmacological methods for structural and functional characterizations.
Molecular mechanisms of TRANSPORTERS
We work on characterizing Na+/H+ exchangers, secondary active transporters crucial for pH regulation in early and late endosomes.
Molecular mechanisms of taste perception
We are characterizing the activation and modulation of membrane proteins involved in taste signaling to delineate their function as well as their therapeutic and diagnostic potential.
NEW TOOLS FOR membrane protein research
Extracting integral membrane proteins from their lipid membranes remains the major bottleneck in their biochemical characterization. The extraction is typically carried out using detergents, but this means that annular lipids or other transiently associated cofactors are lost in the process. The Autzen Group is developing amphipathic copolymers as a tool for structural and functional characterization of integral membrane proteins from native and recombinant sources in what is coined “native nanodiscs”.
LOCATING A CALCIUM BINDING SITE with cryo-em
The transient receptor potential (TRP) channels compose a large, and functionally diverse, superfamily of integral membrane proteins that are ubiquitously expressed and respond to a wide range of chemical and physical stimuli. While calcium permeability is a defining feature for the majority of TRP channels, the melastatin subtype 4 (TRPM4) subtype is exclusively permeable to monovalent cations and activated by intracellular calcium. The gating mechanism of hTRPM4 is unclear, however, using single-particle cryo-EM, we located a conserved calcium binding site in hTRPM4, taking a step further in elucidating how it may respond to calcium.
Funding
The Autzen lab is supported by grants from The Lundbeck Foundation, The Novo Nordisk Foundation, The Carlsberg Foundation, and The Independent Research Fund Denmark.