Autzen Group – Molecular mechanisms of taste signalling, metabolic homeostasis and native nanodiscs

We combine single-particle cryogenic electron microscopy (cryo-EM) for high resolution structural determination with biochemical, biophysical, and pharmacological methods for functional characterization, through e.g. liposomal assays, Surface Plasmon Resonance (SPR), and live-cell assays.

We use SF9 and HEK293 cell lines for large-scale protein production.

We assess protein stability with high throughput fluorescence size exclusion chromatography, Flow Induced Dispersion Analysis (FIDA) and nano-differential scanning fluorometry (nanoDSF).

Taste perception

Sweet, umami, and bitter tastes allow us to enjoy homecooked meals, and Michelin star restaurants. However, taste perception is also tied to survival and helps our bodies identify toxins, maintain nutrition, and regulate gastrointestinal motility.

We are characterizing the activation and modulation of membrane proteins involved in taste signalling 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 characterization in vitro. The extraction is typically carried out using detergents, meaning annular lipids or other, transiently associated cofactors are lost in the process.

We are 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”. 

pH Regulation in Endosomes

Like a fast-paced and interconnected highway, the endosomal trafficking system covers vast expanses inside our cells ensuring cargo is transported from the plasma membrane to the lysosome or recycled and transported back to the cell surface. Mutations in the proteins involved in the recycling system are implicated in debilitating neurodegeneration.

We are characterizing secondary active transporters crucial for pH regulation in early and late endosomes to understand the molecular mechanisms underlying pH regulation in the endosomal trafficking system.

Sensing Acid, Targeting Pain

The sting of a paper cut, the burn of lactic acid in an overworked muscle, the searing pain of inflamed tissue - these sensations all rely on our ability to detect drops in extracellular pH.

Acid-sensing ion channels (ASICs) are proton-gated cation channels that translate tissue acidosis into electrical signals in the peripheral and central nervous system, contributing to nociception, ischemic neuronal death following stroke, and neurodegeneration. Despite their broad therapeutic relevance, ASICs remain a largely untapped drug target.

We are identifying and characterizing small molecules and peptides that modulate ASIC function to advance them as targets for the treatment of pain and neurological disease.