Biophysics Seminar 4 TT7

Talk 1: Engineering Bubbles
Prof Eleanor Stride, Dept of Engineering & NDORMS (Oxford)

Despite extraordinary advances in the development of new drugs and biotechnology, the rates of mortality due to cancer and cardiovascular disease continue to rise. In many cases the problem lies not with the drugs but rather the difficulty in successfully delivering them to the target site. The goal of the research being carried out in the Biomaterials and Bioengineering group is to develop new methods for delivering drugs that overcome these barriers. In particular physical stimuli such as ultrasound and magnetic fields are being used to localise the release and improve the distribution of drugs within tissue using micro and nanoscopic bubbles as delivery vehicles. This talk will present the new techniques that have been developed used to fabricate and characterise these bubbles; and how they are being translated into the clinic.

Talk 2: CryoEM Structures and Implications for Gating of TASK K2P K+ Channels
Peter-Rory Hall, Tucker Group, Biophysics & Kavli Institute for Nanoscience Discovery (Oxford)

TASK-1 and TASK-3 are pH-sensitive Two-Pore Domain (K2P/KCNK) K+ channels. Mutations in the channels are associated with neurodevelopmental channelopathies and hypertensive disorders and are targets for the treatment of disorders including sleep apnea, pain, and atrial fibrillation. The structural basis for gating in TASK-3 channels and the mechanism by which TASK channels sense pH to regulate gating are not fully clear. To understand this, we have resolved a range of TASK cryo-EM structures for both TASK-1 and TASK-3, as well as for common disease-causing variants. Combined with functional studies, these structures not only demonstrate the mechanism of gating but also provide important insights into the structural changes that occur within the pH-sensing mechanism during channel inhibition.