Approaching Synapses with Nanoscale Aptamer-Based Biosensors

Projektbeschreibung

Energiesignale bei neurodegenerativen Erkrankungen sichtbar machen

Neuronen kommunizieren miteinander über spezielle Verbindungsstellen, die als Synapsen bezeichnet werden. Diese energetisch anspruchsvollen Verbindungsstellen werden von Astrozyten unterstützt, die wichtige energiebezogene Moleküle wie Laktat, Glutamin und Adenosin zuführen. Es verdichten sich die Hinweise darauf, dass Störungen bei diesem Energieaustausch zwischen Astrozyten und Neuronen ein häufiges und frühes Merkmal neurodegenerativer Erkrankungen sind. Das ERC-finanzierte Projekt SYNAPTA zielt darauf ab, empfindliche Biosensoren im Nanomaßstab zu entwickeln, die mehrere energiebezogene Moleküle in Echtzeit direkt an den Synapsen detektieren können. Das Forschungsteam kombiniert DNS-Aptamer-Technologie mit fortschrittlicher Mikroskopie, um chemische und elektrische synaptische Aktivitäten abzubilden. Das Projekt wird neue Mechanismen neurodegenerativer Erkrankungen beleuchten und Wege für gezielte Therapien eröffnen.

Ziel

“Given the complex, and multifactorial nature of neurodegenerative pathophysiology, strategies aimed at the synapse could provide a useful addition to the therapeutic toolbox” – this quote by B. Dejanovic et al. published in Nature Reviews Drug Discovery this year, highlights the critical need for innovative tools to probe synaptic function. Synapses, where neurons communicate, are tightly regulated by astrocytes, which manage their energy needs (neuroenergetics). Astrocytes shuttle neuroenergetic molecules (e.g. glutamine, lactate, and adenosine) to meet energy demands. Disruptions in these astrocyte-mediated pathways are now recognized as common features in neurodegenerative disorders, suggesting that impaired neuroenergetics may be at the origin of such diseases. Understanding neuroenergetics is crucial for developing therapies that target the root cause of neurodegeneration, not just its symptoms.

SYNAPTA aims to fill this gap by developing nanoscale biosensors that detect multiple neuroenergetic molecules at synaptic dimensions. To achieve this ambitious vision, we will: 1) isolate receptors (DNA aptamers) that reversibly capture neuroenergetic molecules, 2) create a library of DNA aptamer-based biosensors with ~10 nm spatial resolution, 3) design multiplexed sensors, 4) integrate these biosensors into scanning ion conductance microscopy (SICM) and electrophysiology platforms to enable 5) high-resolution, real-time chemical and electrical mapping of synaptic activity. This system will enable millisecond recordings of neuroenergetic molecules at <10 nm resolution, surpassing current technologies.

Led by my multidisciplinary expertise in aptamer discovery, chemical biosensing, and neural interfaces, SYNAPTA will consolidate these fields to uncover how astrocyte-neuron interactions affect synaptic function and disease progression. SYNAPTA will advance our understanding of neurodegenerative mechanisms and open new possibilities for therapeutic interventions.