14th Cambridge Ion Channel Forum

The Cambridge lon Channel Forum was established in 2011 by Eddy Stevens and Clare Jones as a joint initiative between Pfizer Neusentis and Medimmune.

The concept was to create an environment for industry and academic scientists working within the ion channel field in the Cambridge area to share data and ideas, ensuring all presentations and discussions were based around scientific data with little commercial focus.

The CICF is organised by AstraZeneca, Metrion Biosciences and the British Pharmacological Society.

At this event, Jim Reid will be giving a talk about Domainex's membrane protein platform: 

Enabling Membrane Protein CryoEM with Polymer Nanodiscs: A TRPML3 Case Study

Dr Jim Reid, Domainex

Multi-pass transmembrane proteins such as GPCRs, ion channels, and transporters are central regulators of cellular signalling, communication, and homeostasis. These membrane proteins account for approximately 20–30% of all proteins encoded by sequenced genomes and constitute key therapeutic targets. Despite their significance, recombinant production of stable, functional membrane proteins remains a major bottleneck. Their reliance on a native lipid bilayer environment complicates expression, purification, and structural analysis.

Amphipathic copolymers have enabled detergent-free extraction of membrane proteins into nanodisc assemblies that retain endogenous lipids, offering a more native environment than traditional detergents. Nevertheless, many membrane proteins remain recalcitrant to current polymer-nanodisc methodologies, exhibiting poor solubility, aggregation, or instability that restricts their use in biochemical and structural studies.

Here, we describe a novel, compact fusion tag that substantially improves the behaviour of diverse multi-pass membrane proteins within polymer nanodiscs. Across multiple targets, the tag enhances recombinant yield and confers improved solubility and stability while reducing aggregation. These improvements facilitate higher concentrations suited to downstream biophysical and structural workflows. Applying this approach, we report the first detergent‑free cryo‑electron microscopy structure of the ion channel TrpML3, establishing a route to stabilizing challenging membrane proteins without detergents.