Protein Choreography of the Molecular Compass

Birds, fruit flies and many other animals are equipped with the remarkable ability to sense the Earth's magnetic field by means of a biochemical reaction in cryptochrome proteins. Surprisingly, this protein molecular compass utilises truly quantum effects to respond to changes in the magnetic field as the animal navigates. The molecular basis of how these protein molecules structurally reconfigure in response to planetary magnetic fields, transduced by quantum effects on single electrons within the molecule, is unknown. In migratory songbirds, such as the European robin, Cryptochrome 4 (Cry4) is the protein identified to correlate with magnetosensation. The step of absorbing a photon of light by Cry4 has been shown to be sensitive to magnetic fields in the lab. Yet, little is known about the structure of Cry4 and which conformational changes in its structure transduce the geomagnetic field. Here, we will aim to decipher the inner workings of Cry4 protein as the molecular transducer of our planet's magnetic field by migratory birds. The student will learn a variety of cutting-edge and highly transferable biophysical and computational tools and techniques. This studentship will provide a rare opportunity to become an expert in hydrogen/deuterium exchange mass spectrometry (HDX-MS), using novel prototype instrumentation developed by the Phillips lab at The Living Systems Institute, Univ. Exeter. The student will make millisecond time-resolved measurements of the protein structural dynamics under magnetic stimulation. They will then use these experimental results to seed molecular dynamics simulations (Mulholland Group, Univ. Bristol) and combine this with quantum mechanics calculations (Kattnig Group, Univ. Exeter). As a result, we will produce an experimentally driven molecular movie of the process of Cry4 functional switching with atomistic resolution.