Project description
A rainbow of colours leads to a brain function pot of gold
Since the invention of the X-ray by Rontgen in 1895, medical imaging technology has advanced tremendously. Compared to a century ago, we now have an incredible view of the human body in many dimensions: computer-based image analysis, tracers and contrast agents, multimodal imaging, and the visualisation of function in addition to structure. The EU-funded MAGNIFISCENT project is pushing the frontiers of magnetic resonance imaging (MRI), using a combination of genetics and fluorescence to yield a multicoloured MRI of the brain. Not only is MAGNIFISCENT able to image the interactions of different cell types in vivo, but the team plans to get the resolution down to the single-cell level. Non-invasive high-resolution imaging of functioning cells in vivo is taking its next evolutionary step.
Objective
Imaging defined cells, over extended time, depends on signal strength, stability, accessibility and specificity. Whereas light-microscopy (LM) can provide these, it does not allow imaging of entire intact tissues; imaging-depths and area-size are restricted, and not easily obtained through skin and bone. Magnetic Resonance Imaging (MRI) outperforms LM in these instances; providing images of large-fields-of-view (i.e. mesoscale), at any depth, easily across bone. Nevertheless, MRI suffers from low signals, spatial resolution and cannot detect specific biological targets. To remedy these shortcomings, and significantly extend the capabilities of MRI, we propose a novel chemo-genetic approach—MAGNIFISCENT (MAGNetic Including Fluorescence Imaging of Select Cells with ENzymatic Tags)—to jointly image multiple defined cellular-targets by MRI and LM. In parallel thrusts, we will synthesize a novel family of multifunctional, membrane-permeable, liganded-Contrast-Agents (CA; patented) that irreversibly bind original genetically-encoded enzymatic tags (eTags). When several eTags are expressed in various cells, each will bind its corresponding liganded-CA bearing a unique MRI-signature (‘color’); affording multicolor-MRI of the brain. To mitigate hurdles of expression, we introduce enrichment, an elegant scheme to increase binding-surface for MFS-agents. We estimate it to increase resolution of MRI to the single-cell level. Lastly, developing split-eTags will enable imaging cellular interactions of up to four different cellular populations jointly, a feat never shown before for MRI. We develop an innovative targeted-recombination scheme to ENTRAP neurons destined for apoptosis; a hallmark of neurodegeneration. Together, when combined, select targets will be irreversibly ‘tagged’ for long-term multimodal imaging at high resolutions. The multidisciplinary nature of my group ensures our success in developing this versatile technology for studying the brain in health and disease.
Fields of science
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Funding Scheme
ERC-STG - Starting GrantHost institution
32000 Haifa
Israel