Quantum Sensing in Nature and Synthetic Biology

The annual migration of many animals over vast distances represents one of the most impressive of nature’s spectacles. The European robin, for example, flies alone at night from Northern and Central Europe as far as North Africa. In addition to visual cues including the sun and stars, the evidence is clear that this expert navigator senses and uses both the strength and inclination (angle) of the Earth’s magnetic field on its journey. Our project seeks to elucidate the fundamental principles that govern this animal magnetosense, and to explore how we might engineer this property for new technologies in biomedicine. Quite how a living creature senses a weak magnetic field is far from obvious. The leading hypothesis is based on a protein called cryptochrome located in the animal’s eye. Upon its photoexcitation, two “radicals” are formed. These short-lived species have unpaired electrons, and therefore a property called “spin”, dictating the ways in which they interact with each other as well as with external magnetic fields. In this way the magnetic field influences onward reactions triggering signalling cascades, leading ultimately to a neuronal response: the animal “sees” the magnetic field. Yet, while both animal behaviour and spectroscopic studies provide strong support for this quantum biology mechanism, we have very limited insight into the magnetic signalling cascade between quantum step and the animal’s response. Here we propose an interdisciplinary approach which will allow us to obtain a holistic understanding of the magnetic sense, from the first appearance of a magnetic effect on the cryptochrome’s radicals to the neural activity and behaviour of living mice. Diverse cryptochromes will be investigated: from plants to insects, birds to mammals, in order to identify similarities and key differences in the transduction pathway. To do so we will: 1) design ultra-sensitive spectroscopic tools to observe the very first magnetosensitive quantum steps involving the two short-lived radicals in cell-mimicking environments, 2) employ biophysical techniques to trace how this initial magnetoresponse translates to changes in protein structure and consequently the cryptochrome’s interaction with any signalling partners, 3) develop and use in-cell techniques to follow these magnetosensitive processes in cells, in particular the retinal cells of birds and mammals, before we record the neuronal responses in the retina, subsequent brain circuits and behaviour of living mice. Finally, 4) we will employ our obtained knowledge of magnetosensitive proteins to develop “magnetogenetic” biotechnologies. We will employ directed-evolution strategies to engineer designer magnetosensitive proteins (including those that do not require an external light source) allowing for magnetic control of processes deep in tissue. We will use our engineered proteins for both imaging and actuation of cellular processes in vivo by magnetic field exposure. The outcomes of this proposal are thus a detailed understanding of the origins of the animal magnetosense, and the pioneering developments of magnetogenetic technologies.