Description du projet
Un arc en ciel de couleurs dévoile un trésor de fonctions cérébrales
Depuis l’invention des rayons X par Rontgen en 1895, la technologie de l’imagerie médicale a fait des progrès considérables. En un siècle, nous avons acquis une visibilité incroyable sur le corps humain dans de nombreuses dimensions: l’analyse informatisée d’images, les traceurs et les produits de contraste, l’imagerie multimodale, ainsi que la visualisation des fonctions en complément de la structure. Le projet MAGNIFISCENT financé par l’UE repousse les limites de l’imagerie par résonance magnétique (IRM) en combinant la génétique et la fluorescence afin de générer un IRM multicolore du cerveau. MAGNIFISCENT est non seulement capable de produire des images des interactions entre différentes cellules in vivo, mais l’équipe compte également affiner la résolution au niveau cellulaire. L’imagerie haute résolution non-invasive de cellules fonctionnelles in vivo est sur le point de faire un pas de géant.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
32000 Haifa
Israël