HE ERC Proof of Concept Grant 2026-2027

An RNA aptamer-based tool for the detection of pathological protein aggregates in biofluids

Abstract: The AptALS project aims to develop a highly sensitive and scalable RNA aptamer-based kit for detecting TDP-43 aggregates, a key biomarker in ALS. The kit consists of 3 main components: (i) biotinylated RNA aptamers that selectively bind aggregated TDP-43, (ii) a detection system (fluorescence or chemiluminescence) to quantify binding events, and (iii) a modular assay format compatible with ELISA-like workflows, allowing seamless integration into clinical laboratories. By leveraging our patented aptamers, we will validate their performance in a standardized detection assay, ensuring clinical robustness. Unlike conventional antibody-based methods, RNA aptamers offer superior specificity and adaptability, enabling non-invasive, early-stage ALS detection. This innovation fills a critical gap in ALS diagnostics, replacing invasive lumbar punctures and costly neuroimaging with a cost-effective, scalable alternative. The AptALS project will focus on three key objectives: (i) assay validation, (ii) optimization of detection methods (fluorescence vs. chemiluminescence), and (iii) benchmarking with ALS patient samples. The project is led by a multidisciplinary team with expertise in biophysics, molecular biology, and computational modeling, supported by IIT’s state-of-the-art genomics, proteomics, and microscopy facilities to ensure technical rigor and scalability. Beyond its scientific impact, AptALS delivers significant societal and economic benefits. Early ALS detection can enable timely intervention, improve patient care, and reduce healthcare costs. The diagnostic kit is designed for B2B distribution, targeting hospitals, diagnostic laboratories, and pharmaceutical companies for clinical trials and patient stratification. Positioned at the forefront of neurodegenerative disease diagnostics, AptALS is poised for strong commercial adoption, bridging the gap between research and real-world clinical application, fostering innovation, and advancing ALS care.

Total budget: 150.000,00€

Total contribution: 150.000,00€

H2020 ERC - Synergy Grant 2020-2027

ASsembly and phase Transitions of Ribonucleoprotein Aggregates in neurons: from physiology to pathology

Abstract: Recent works indicate the pathogenic relevance of altered RNA metabolism and aberrant ribonucleoprotein (RNP) assembly in several neurodegenerative diseases, such as Amyotrophic lateral sclerosis. How defective RNPs form, what are their integral components and which events trigger their appearance late in life are still unsolved issues. While emerging evidence indicates that mutations and post-translational modifications of specific RNA-binding proteins (RBPs) induce liquid-solid phase transition in vitro, much less is known about the in vivo properties of RNP assemblies and which role RNA plays in their formation. ASTRA will combine sophisticated imaging-derived RNP complex purification with innovative computational approaches and powerful genetic tools to unravel the biophysical properties and composition of RBP complexes and how they are modified in disease conditions. Through the development of new imaging and optical methods we plan to study how RNPs separate in liquid and solid phases in cells, in tissues (retina) and animal models and to characterize their RNA and protein components in physiological and pathological states. Exploiting the novel finding that non-coding RNAs act as scaffolding molecules for RNP assembly, we will investigate how such RNAs control the dynamic link between RNP formation, intracellular sorting and function. In a genuine interdisciplinary team effort, we will reveal how the architecture and localization of cytoplasmic RNP complexes are controlled in motor neurons and affected in neurodegeneration. We plan to develop novel advanced microscopy methods to monitor formation of aberrant RNPs in vivo and we will explore new molecules to impede pathological cascades driven by RNP assemblies. In conclusion, ASTRA will allow us to gain a comprehensive understanding of RNP function and dysfunction; we will use this knowledge to develop new therapeutic strategies that will impact on several protein-misfolding neurodegenerative diseases.

Total budget: 5.602.894,55€

Total contribution: 5.602.894,55€