Talk 1: DNA nanostructures as tags for electron cryotomography
Dr Emma Silvester; Baker Group, Dept. of Biochemistry & Kavli, University of Oxford

Abstract:
Cryo-electron tomography enables us to visualize biological molecules in their native biological environment at high resolution. At present, the challenge lies in identifying specific molecules in crowded tomograms due to sample complexity and low signal to noise ratios. We have introduced a novel tagging method for cryoET that overcomes these hurdles (Cell 2021). Our approach uses DNA origami to create ‘molecular signposts’ capable of precisely targeting molecules of interest, enabling the identification of individual proteins in tomograms without relying on traditional metal clusters. We have since expanded this methodology to diverse sample types and protein targets, broadening its applicability. Our current focus is applying this technology for intracellular applications.

Talk 2: Developing a toolbox of nanobodies to study K2P channels
Kathryn Smith; Tucker Group, Biophysics & Kavli, University of Oxford

Abstract:
Two pore domain potassium channels, K2P channels, are a family of leak channels which maintain the negative membrane potential of the cell. They are regulated by a wide range of factors and are involved in diverse functions such as smooth muscle relaxation and pain sensing. Channel regulation converges on a gating mechanism at the selectivity filter which is found in all K2P channels as well as voltage gated hERG channels and calcium – activated big-conductance potassium type channels¹ making design of specific drugs challenging. Biologics such as nanobodies can combine highly specific binding with interactions that modulate the activity of the channel so they offer a potential solution to the design of specific modulators against different channels which share a common gating mechanism.