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Approaching Synapses with Nanoscale Aptamer-Based Biosensors

Project description

Visualising energy signalling in neurodegeneration

Neurons communicate with each other through specialised connection sites known as synapses. These sites are energetically demanding and are tightly supported by astrocytes, which supply key energy-related molecules such as lactate, glutamine, and adenosine. Accumulating evidence suggests that disruptions in this astrocyte-neuron energy exchange are a common and early feature of neurodegenerative diseases. The ERC-funded SYNAPTA project aims to develop sensitive nanoscale biosensors capable of detecting multiple energy-related molecules in real time, directly at synapses. The research team will combine DNA aptamer technology with advanced microscopy to map chemical and electrical synaptic activity. The project will shed light on new mechanisms of neurodegeneration and open avenues for targeted therapies.

Objective

“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.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-STG

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Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution
€ 1 499 130,00
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland
Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 130,00

Beneficiaries (1)