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Magnetoreception

Several migratory animal species use the magnetic field of the earth to navigate during migration. In particular, this includes birds which migrate nocturnally, some species of fish, and the North American monarch butterfly. These species are less able to use visual navigation. However, there is debate about the mechanism by which this internal compass works.

Overview

The two leading theories of magnetoreception can be categorised as a magnetite-based system which has been found to be involved most significantly in bacteria.The second, more complex proposed mechanism suggests that select biological molecules can generate radical pairs which are sensitive to the Earth’s magnetic field [1]. Suggested by Thorsten Ritz et al. [2], this was posited as a theoretical model that has since been inspiration for several in vivo studies.

Behavioural experiments by Wolfgang and Roswitha Wiltschko in the European robin model seems to complement this proposed mechanism of the radical pair mechanism of the avian compass [3]. However, though theoretically compelling, this mechanism still lacks the conclusive empirical biological evidence of the fundamental understanding of the mechanism behind the avian compass.

Current projects

Project description

Cryptochrome, the putative magnetosensor molecule, has been studied in the fields of chronobiology and circadian rhythmicity, but recently gained popularity for its blue-light receptor function and subsequent production of a radical pair. At the Leverhulme Quantum Biology Doctoral Training Centre, Edeline will be investigating the role of cryptochrome in magnetoreception and investigating the mechanism and interactions through which cryptochrome conveys its magnetosensor function and if this differs between species-specific variants of the protein via in vivo and in vitro characterisation.

Future scope may lead to the use of cryptochrome as a potential (magneto-)optogenetic tool in biotechnology applications.

Postgraduate researcher

Supervisors

Project description

TB is an ongoing problem in developing countries as well as becoming more of problem in industrialised countries, being accountable for 1.5 million deaths per annum.

The biggest challenges being faced are multidrug resistant (MDR) strains of mycobacterium Tuberculosis (TB causing pathogen) that are resistant to antibiotic therapy. Isoniazid (isonicotinoyl hydrazide, INH) is one of the front-line drugs used in the treatment of TB, being able to inhibit mycolic acid synthesis and consequentially mycobacterial cell wall formation. Unfortunately, this has limited efficacy towards MDR strains, making effective chemotherapy challenging.

This project aims to look at new approaches to drug therapy to resolve these issues. Read more about this project.

Watch an interesting seminar on radical pair mechanism of magnetoreception via YouTube.

Postgraduate researcher

Supervisors

Project description

Could quantum biology provide the tools to cope with tuberculosis, a disease which affects about 10 million in the world today and kills about 1.5 million of them annually?

Spin physics is central to the radical pair mechanism of the avian compass and is probably the fastest growing field within quantum biology.

Isoniazid (isonicotinylhydrazide, INH) is a key antibiotic used in the treatment of tuberculosis (TB). It is a prodrug that inhibits the formation of the mycobacterial cell wall by inhibiting the synthesis of mycolic acids. Isoniazid must be activated by KatG, a bacterial catalase-peroxidase enzyme in Mycobacterium tuberculosis and other bacteria.

The precise reaction mechanism remains controversial and may involve the formation of a radical pair intermediate. The large 13 C hyperfine coupling of the substituted [acyl-13C]-INH radical is expected to enhance the singlet-triplet interconversion rate of this radical pair by allowing simultaneous electronic and nuclear spin 'flips' in the isoniazid derived radical, thereby enhancing the formation of the INA-NAD adduct.

The aims of this project are to identify possible spin dependent reaction pathways, build and refine in silico models of the spin dynamics of INH action (e.g. based on the radical pair mechanism), and generate predictions and suggest protocol to detection of the effects of isotopic substitution, static magnetic field effects, and possibly oscillatory magnetic field effects that may be tested in the experimental project.

Postgraduate researcher

Supervisors

Research team

University of Surrey

Claudio Avignone Rossa FRSB profile image

Dr Claudio Avignone Rossa

Professor of Systems Microbiology

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Ed D'Souza

Postgraduate Research Student

Brendan Howlin profile image

Dr Brendan Howlin

Reader in Computational Chemistry

Youngchan Kim profile image

Dr Youngchan Kim

Lecturer in Quantum Biology

Johnjoe McFadden profile image

Professor Johnjoe McFadden

Professor of Molecular Genetics, Associate Dean (International)

Lucy Ridout profile image

Lucy Ridout

Postgraduate Research Student

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Charlotte Vale

Postgraduate Research Student

External collaborators

Jose Jimenez Zarco profile image

Dr Jose Jimenez Zarco

Senior Lecturer in Synthetic Biology - Imperial College London

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Dr Alex Jones

Principal Research Scientist - National Physical Laboratory

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Dr Daniel Kattnig

Senior Lecturer - University of Exeter

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Professor Alexandra Olaya-Castro

Professor of Physics - University College London

References

Magnetosensing of the cryptochrome molecule

[1] Hore PJ, Mouritsen H. The radical-pair mechanism of magnetoreception. Annual review of biophysics. 2016 Jul 5;45:299-344.

[2] Ritz T, Adem S, Schulten K. A model for photoreceptor-based magnetoreception in birds. Biophysical journal. 2000 Feb 1;78(2):707-18.

[3] Ritz T, Wiltschko R, Hore PJ, Rodgers CT, Stapput K, Thalau P, Timmel CR, Wiltschko W. Magnetic compass of birds is based on a molecule with optimal directional sensitivity. Biophysical journal. 2009 Apr 22;96(8):3451-7.

Quantum and drugs: Spin dynamics in an antibiotic

[1] Hore, P. and Mouritsen, H., 2016. The Radical-Pair Mechanism of Magnetoreception. Annual Review of Biophysics, 45(1), pp.299-344.

[2] Kamachi, S., Hirabayashi, K., Tamoi, M., Shigeoka, S., Tada, T. & Wada, K. 2015. Crystal structure of the catalase–peroxidase KatG W78F mutant from Synechococcus elongatus PCC7942 in complex with the antitubercular pro-drug isoniazid. FEBS letters, 589, 131-137.

[3] Timmins, G. and Deretic, V., 2006. Mechanisms of action of isoniazid. Molecular Microbiology, 62(5), pp.1220-1227.

[4] Zhang, Y., Heym, B., Allen, B., Young, D. & Cole, S. 1992. The catalase—peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature, 358, 591-593.

[4] Bertrand, T., Eady, N., Jones, J., Jesmin, Nagy, J., Jamart-Grégoire, B., Raven, E. and Brown, K., 2004. Crystal Structure of Mycobacterium tuberculosis Catalase-Peroxidase. Journal of Biological Chemistry, 279(37), pp.38991-38999.

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Leverhulme Quantum Biology Doctoral Training Centre (QB-DTC)
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University of Surrey
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