Community Research and Development Information Service - CORDIS



Project ID: 311552
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - MAGNETOGENETICS (Reverse engineering the vertebrate molecular machinery for magnetic biomineralisation)

It is the goal of the bioengineering project Magnetogenetics to lay the groundwork for biomagnetic interfaces for non-invasive readout and actuation with genetically controlled spatiotemporal precision via magnetic fields. This magnetogenetic technology has the great advantage over photon-dependent methods in that it can penetrate much deeper into biological tissue than light-dependent methods such as fluorescence or optoacoustic molecular imaging and optogenetics. Also, magnetogenetics allows for the ability to directly exert mechanical movements. As compared with chemogenetic methods that can also reach deeper tissue, Magnetogenetics offers higher temporal precision.
To enable magnetogenetic technology, we pursue a comprehensive strategy that incorporates both a biomimetic approach aimed at reverse-engineering naturally occurring magnetic biomineralizations as well as a bioengineering/synthetic biology approach that recombines and modifies known molecular players involved in metal-transportation and organization such as in iron homeostasis.
We have set up a comprehensive gene expression system in cultured cells as well as in zebrafish models that allows us to express multiple genes with controlled stoichiometry such that ‘molecular pathways’ can be constructed. We complemented this with an analytical pipeline that allows for measurements of net metal accumulation, its effects in NMR, magnetic sorting and hyperthermia as well as subcellular metal distribution and organization using Raman and Electron Microscopy as well as state of the art microscopic measurements of magnetic fields.
Using this comprehensive pipeline, we have determined the most effective and non-toxic way to achieve substantial intracellular iron uptake and storage, an important feature for downstream metal organization. Besides evaluating engineered proteins modified from various bacterial and eukaryotic origin, we are also feeding genes into this pipeline which we identify from model organisms tested for their ability to perceive earth’s magnetic field. Importantly, we focus on filling in the crucial mechanistic gaps - also for various published claims - by revealing the exact conversion from the magnetic field to the molecular signal of interest.
In summary, we have established a comprehensive pipeline to systematically and mechanistically evaluate genetic modifications to render eukaryotic cells responsive to magnetic fields such that they can be read-out and actuated non-invasively across entire live organisms. We have engineered a set of genetic constructs that we carefully investigate with respect to the subcellular and molecular effects on metal biomineralization as well as their uses for exerting various forms of magnetogenetic control.

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