Descripción del proyecto
Un arcoíris de colores conduce a una mina de oro de la función encefálica
Desde la invención de los rayos X por Rontgen en 1895, se ha producido un tremendo avance en la tecnología de imagenología médica. En comparación con hace un siglo, ahora contamos con una increíble vista del cuerpo humano en diversas dimensiones: análisis de imágenes por ordenador, trazadores y agentes de contraste, imagenología multimodal y la visualización de la función además de la estructura. El proyecto financiado con fondos europeos MAGNIFISCENT está ampliando los límites de la resonancia magnética (RM) mediante una combinación de genética y fluorescencia para obtener una RM multicolor del encéfalo. MAGNIFISCENT no solo permitirá obtener imágenes de las interacciones de distintos tipos de células «in vivo», sino que también tiene previsto alcanzar un nivel de resolución celular. La imagenología no invasiva y de alta resolución de las células en funcionamiento «in vivo» está dando su próximo paso evolutivo.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
32000 Haifa
Israel