Welcome to the Sigworth Laboratory
Work in our laboratory centers on the function and structure of ion channel proteins. Ion channels are molecular transducers that switch on and off electrical currents that are carried by ions across biological membranes. Depending on the ion channel type, the switching action is controlled by voltage, mechanical forces, or the binding of particular small molecules (ligands). We call these channels voltage-gated, mechanosensitive and ligand-gated channels, respectively.
Voltage-gated and ligand-gated ion channels are well known for their role in electrical activity of nerve cells, but ion channels are found in many other places too. Ion channel defects are responsible for disorders like Cystic Fibrosis, cardiac arrhythmias, and some kinds of hypertension and kidney disease.
- Our work concerns a few particular channel types. One is a voltage-gated potassium channel, called Shaker after the name of a misbehaving fruit fly that lacks this channel's gene. Another is a member of the same voltage-gated channel family, but is also controlled by ligands, namely calcium ions. When open it allows a large current of potassium ions to flow, and so is known as the BK (big K+) channel. The third is an intracellular calcium-release channel called the IP3 receptor. It opens in response to the binding of an important intracellular messenger molecule, inositoltrisphosphate, and releases calcium ions from intracellular stores.
Patch-Clamp Advances in biology come from advances in instrumentation and techniques. We are working in two areas of technology development. We are developing fully integrated patch-clamp amplifier systems that would facilitate the fabrication of automatic, high-throughput recording systems that can patch 384 or more cells in parallel. To simplify the structure determination of membrane proteins (such as ion channels) we are pursuing technical advances in electron microscopy of frozen single-molecule specimens (single-particle cryo-EM) and the mathematical reconstruction of 3D structures from electron microscope images.