Kattnig Group Here you will find a brief summary of our research interests in spin-dependent biophysics. Fundamentally, biological systems rely on the rules of quantum mechanics as they are ultimately defined at the molecular and sub-molecular scale where quantum phenomena become evident. However, going beyond fundamental presence, quantum biology asks the question: does life crucially rely on quantum phenomena by utilising it to an advantage for physiological function? Recently, studies to address this question have seen rapid growth due to an increase in computational and experimental capability, and the development of advanced theoretical techniques. Yet, there remain many open questions that must be solved. Here, in the Kattnig group we focus on the theoretical description, computational simulation, and experimental assessment of magnetic field effects (MFEs) that are dependent on the property of quantum spin in chemical reactions underlying biological processes and investigating the role that quantum mechanics plays. Spin-dependent Magnetoreception Magnetoreception, the ability of some animals to sense the Earth’s weak ~50 micro-tesla magnetic field is one of the grand puzzles of modern science and represents a prominent biological magnetic field effect. One leading hypothesis, centred on the radical pair mechanism (RPM), suggests a compass sense that depends on the magnetic field sensitive quantum spin dynamics of a pair of radicals (a molecule containing at least one unpaired electron) that are formed by a photo-induced electron transfer reaction in the flavoprotein cryptochrome (see Fig. 1). Our magnetoreception research includes: investigating the limit of realistic system complexity, relative orientation of radicals, and inter-radical interactions, understanding the role of the external environment, extending to new models, controlling sensitivity and quantum features, and experimental tests. An overall aim of ours is to elucidate the potentially quantum nature of magnetoreception and more generally understand principles of spin dynamics that can be utilised in future technologies, such as quantum sensors, and medical applications. Fig. 1: Structure of an avian cryptochrome (PDB identifier: 6PU0, Columba livia), including the central electron transfer chain comprising four tryptophans (W) labelled A (W395), B (W372), C (W318) and D (W369) and ending in the surface exposed tyrosine Y319. Photo-excitation of FAD in cryptochrome initiates consecutive electron transfer reactions of adjacent donors/acceptor pairs (red arrows), producing sequential radical pairs of the form [FAD•− / W•+] and possibly [FAD•− / Y•]. The well separated radical pairs involving WC and WD implicated with magnetoreception. Alternative radical pairs have been discussed. Open quantum systems The nontrivial contribution that the external environment often plays in quantum biology necessitates our treatment of systems as so-called open quantum systems (OQS). A prime example of this is radical pair dynamics within the protein cryptochrome. Quantum phenomena such as spin coherence are thought to be washed out through their coupling to any hot, wet and noisy environment, as they are in most quantum technology applications. This would suggest a diminishing of magnetosensitivity in cryptochrome. Surprisingly, studies suggest that the spin relaxation resulting from the protein environment can, under certain conditions, enhance the performance of a cryptochrome-based magnetic compass sensor. In the group we are working on understanding the role of the external environment under the Markovian (memoryless) limit of these studies and beyond to non-Markovian behaviour, which we hypothesise can act as a driver of spin dynamics (see Fig. 2) to counterintuitively enhance the coherence and sensitivity of the system. We employ OQS theory, supported by simulations of protein dynamics, to decipher magnetoreception based on radical-pairs and triads, and more generally understand OQS spin dynamics and optimisation. Fig. 2: Driven radical motion r(t) of a radical pair of cryptochrome allows the magnetic field sensitivity to be restored, and even enhanced, despite the presence of detrimental inter-radical interactions. We are now investigating if enhancements such as these may be realised by components of the motion of the protein environment. Three-radical effects While a model of magnetic field sensitivity based on radical pairs is well established (i.e. the Radical Pair Mechanism), magnetic field effects (MFEs) on radical pairs in low magnetic fields are often strongly attenuated by inter-radical interactions and decoherence processes. Our research suggests that the magneto-sensitivity of radical reactions can be significantly amplified in systems of three and more radicals. In our group we have investigated models of radical triads (see Fig. 3) showing that: remarkable MFEs can be realised due to “bystander radicals” via the dipolar interaction. That principles generalise to n-radical systems for which geometrical symmetry-breaking can further amplify the magnetic field sensitivity. Even more remarkably, the extension of radical pairs by a third reactive “scavenger radical” can overcome the sensitivity suppression arising from inter-radical interactions and render the reaction immune to fast spin relaxation in one of the radicals. This models may credibly facilitate light-independent oxidation reaction schemes for cryptochrome magnetoreception and other biological processes, the existence of which is still discussed controversially due to its necessary involvement of quickly relaxing species. Our ongoing study of these models includes understanding and controlling benefits of driving and protein motion. Beyond magnetoreception we are exploring three-radical MFEs in other biological processes (e.g. lipid-peroxidation and hypomagnetic field effects on neurogenesis), and how they may provide principles for quantum sensing devices. Fig. 3: (a) Structure of pigeon cryptochrome 4 (PDB: 6PU0). (b) The tryptophan tetrad and relevant radical sites are enlarged and the reaction pathways, including both photoreduction and re-oxidation, are shown by the arrows. Electron-electron dipolar interactions (EED) and radical scavenging can vastly enhance the magnetosensitivity. Openings We are always looking for enthusiastic talents to join our group! PhD Studentships Fully funded PhD studentships for UK and international applicants are available on a regular basis. Places are competitively filled. Please get in touch if interested to discuss opportunities and project topics. Fully funded PhD position (LSI): Peptide magnetosensors: new quantum mechanisms to explain and engineer magnetic field sensitivity in biological systems Magnetoreception is a remarkable and puzzling trait. It is fundamental for navigation and migration in many animals and present in some non-migrating organisms. Yet, despite intense research we do not know how organisms actually sense magnetic fields and how they respond to them. The last two decades have established the blue-light responsive flavoprotein cryptochrome (CRY) as the primary candidate magnetoreceptor. CRY is believed to transduce magnetic information to the cell via a quantum effect on a radical pair generated in a light-induced electron transfer reaction between a CRY-bound Flavine Adenine Dinucleotide (FAD) and a conserved tryptophan residue in CRY. However, there is considerable debate about the nature of the radical pair. A recent study [Nature 2023, 615(7950):111-116] has demonstrated in vivo that the CRY C-terminal (CRYCT) without the canonical FAD binding site can potentiate the magnetoresponse of free-FAD within fruit fly neurons. This observation represents a fundamental shift in our understanding of biological magnetoreception, as it highlights an unexpected pathway to magnetosensitivity, enabled by a peptide of only 52 amino acid residues. While again coherent spin dynamics in a radical pair intermediate are assumed crucial, the mechanistic details of how this unexpected magnetosensitivity is realized are currently unknown. The aim of this project is to shed light onto the cryptic magnetosensitivity of cryptochrome and, in particular, its CRYCT through in vitro investigations of the protein/peptide using optical spectroscopy and time-resolved hydrogen-exchange mass spectrometry in combination with molecular modelling. This project will be suitable for outstanding students with a background in biophysics, physical chemistry, biochemistry, or molecular biology eager to engage in an interdisciplinary project involving a broad range of approaches ranging from protein engineering, over advanced spectroscopy to modelling and quantum mechanics. The project emphasis can be fitted to the candidate’s interests and training. Prior knowledge in all aspects is not required, but applicants will need to show eagerness and ability to engage with inter-disciplinary research at the LSI. Full training will be provided, and the student will be embedded in both the Kattnig and Phillips research groups, facilitating continuous support from colleagues. Please contact the project supervisors, Daniel Kattnig (d.r.kattnig@exeter.ac.uk) and Jonathan Phillips (jj.phillips@exeter.ac.uk), to discuss details and options. This project will be carried out in alliance with the discoverers of the CRYCT-effect, Charalambos Kyriacou, Ezio Rosato (University of Leicester), Alex Jones (NPL) and Richard Baines (University of Manchester), who will undertake complementary studies, predominantly in vivo. Postdoc Opportunities We are currently recruiting a Postdoctoral Research Fellow to participate in the research project “Three, not two, radicals: Revealing the true mechanism of cryptochrome magneto-sensation”. This BBSRC funded post is available from 1/1/2024 to 31/12/2024. The successful applicant will undertake biophysical studies, in particular, millisecond time-resolved HDX mass spectrometry and laser-induced fluorescence spectroscopy, to study magnetic field effects of cryptochrome and related proteins. Details are available here. Fellowship Applications We are happy to support applications and host recipients of personal research fellowships (e.g. URF, Marie Curie, 1851, Newton International).