A new technology to probe molecular interaction in cells at high throughput

Project Information

DiffusOMICS

Grant agreement ID: 101158292

DOI

10.3030/101158292

Project closed

EC signature date 8 March 2024

Start date 1 April 2024

End date 30 September 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

KUNGLIGA TEKNISKA HOEGSKOLAN
Sweden

Periodic Reporting for period 1 - DiffusOMICS (A new technology to probe molecular interaction in cells at high throughput)

Reporting period: 2024-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

Protein aggregation and large complex formation are known to be fundamental for the progression of many neurological disorders. Studying such dynamic processes is therefore key for developing new drugs
and treatments to tackle imminent challenges in neuroscience and medicine. Despite the wide range of applications that benefit from the accurate readout of molecular interactions and dynamics, methods to unveil such processes in the native context and at high throughput
are scarce . This technological void forces researchers to use laborious methods to infer information on said mechanisms, frequently resorting to simplified model systems. This not only hinders the pace of
research and escalates costs but also runs the risk of overlooking potential interferences inherent in the native systems. Developing technologies and assays able to reveal protein-protein interaction and aggregation as
well as other types of structural alterations in a direct, robust, and cheap way inside relevant biological environments should therefore be a key focus of future neuroscience research.
In this project we provide a technological solution capable of measuring protein interactions directly in live neuronal cells and tissues, revealing selected protein n-meric states from oligomers to large complex aggregates.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project we invented, design and built a new technology capable to detect oligomers and their rotational dynamics.
The prototype set-up is up and running in the Testa laboratory.
With a completely new type of optical read-out we combined spatial selectivity with dynamic information for the study of proteins in living cells.
We demonstrated that our system can probe the dynamics of larger macromolecules and molecular complexes with spatial selectivity.
The target was expressed in neuronal cells showing great potential for neurodegenerative research.
Overall, the technology can be used for the screening or validation of new drugs for some of our most severe and costly public health challenges.

The research done is very much in agreement with the proposed objectives and included specifically:
WP1-2 Hardware and Software development and WP3 Proof of concept application in neuronal cells.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Further research

With the prototype ready we are now extending the potential range of application by targeting different type of oligomers.
We initiated collaborative work on different neurodegenerative hallmark such as tau and aplha syn.

The next grand challenge is data handling and developing analysis tools to extract and correlate and integrate different quantitative information and physical parameters.


Access to markets and finance and commercialisation

Based on the results of this project we were selected for a Deep Tech Program at KTH and achieved funding to mantain the patent and reach the internationalization level.