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Computation driven development of novel vivo-like-DNA-nanotransducers for biomolecules structure identification

Periodic Reporting for period 1 - iSenseDNA (Computation driven development of novel vivo-like-DNA-nanotransducers for biomolecules structure identification)

Período documentado: 2022-10-01 hasta 2023-09-30

The primary goal of iSenseDNA is to innovate the realm of bio-molecular sensing by crafting personalized DNA structures, essentially serving as "translators" to unveil concealed information related to bio-molecular processes.
The groundbreaking methodology spearheaded by iSenseDNA involves the utilization of "DNA nanotransducers" (DNA-NTs) and their dynamic interactions with proteins.
This pioneering approach has the potential to revolutionize medical diagnostics and treatment modalities.

To accomplish this overarching objective, the project is strategically broken down into the following intermediate goals:

A. Develop a comprehensive repertoire of enzymes featuring 'novel activities' to modify DNA structures.
B. Engineer and demonstrate tailored DNA-NTs covering a diverse spectrum of topologies pertinent to cellular processes. These DNA-NTs are also equipped with specific DNA sequence modifications to facilitate interactions with targeted proteins.
C. Attain an in-depth understanding of the interactions between DNA-NTs and proteins, closely monitoring the structural alterations in DNA when bound to proteins.
D. Validate and explore potential applications of DNA-NTs both before and after interactions with model proteins, such as GCN4 and alpha-synuclein.

These intermediate objectives collectively propel iSenseDNA's advancements in the field of bio-molecular sensing, laying the groundwork for groundbreaking developments in diagnostics and therapeutics.

This project stems from the recognition of pressing challenges and needs in bio-molecular research.
By creating custom DNA structures and utilizing innovative DNA-NTs, iSenseDNA aims to address the intricate details of cellular processes, with a particular focus on medical applications.
The project envisions contributing significantly to the field, offering solutions to identified problems in the context of evolving political and strategic landscapes.

The anticipated impact of iSenseDNA's results is substantial, as successful implementation could lead to transformative changes in medical diagnostics and therapeutic interventions.
During the initial 12 months of the project, the iSenseDNA team has concentrated its efforts on a variety of technological aspects essential for realizing the project's ultimate objective, which is the creation and analysis of custom-made DNA-NTs both independently and in the presence of model proteins. The primary activities included:

(i) Engineering the enzymes to enable the production of positively supercoiled DNA.
(ii) Analysis of specific sequences to be incorporated into the customized DNA-NT and design of the initial DNA-NT model.
(iii) Development of the first DNA-NTs with diverse topologies for initial spectroscopic evaluation.
(iv) Calculation of preliminary spectral signals of DNA and molecules studied within this project.
(v) Building the ultrafast 2D noncollinear spectroscopy set-up.
(vi) Designing and fabrication of photonic chip.
(vii) Generation of model proteins and in-depth analysis of their properties and behaviors to study the interaction with the designed DNA-NTs.

Additionally, the consortium has actively planned and engaged in dissemination activities, particularly by publishing scientific findings related to iSenseDNA in various open-access publications.
The team has organized a first workshop to present the core business of the project to the scientific communities and also participated in scientific conferences and events to introduce the overarching concept of iSenseDNA to a broader audience.
The platform envisioned in this project represents an innovative approach to constructing essential components and seamlessly integrating them. The primary aim is to create a unique sensing technology that implements advanced real-time diagnostics, enabling the identification and correlation of molecular structures and biological functions within a single system. This pioneering approach holds the potential to unlock specific applications in the domains of diagnostics and drug discovery.
iSenseDNA has the potential to significantly impact several scientific areas and markets, including:
(i) Bioinformatics and advanced computational methods, encompassing molecular dynamics at both classical and quantum levels, as well as machine learning.
(ii) Biotechnology, with a particular focus on protein engineering and molecular biology.
(iii) Advanced optical spectroscopy, including micro- and nanophotonics.
(iv) Nano-fabrication, specifically for micro/nano photonic chip development.
(v) Nanomedicine, exploring the application of nanoscale materials in medical contexts.
In comparison to the existing state-of-the-art in structural biology and diagnostics, iSenseDNA introduces the integration of costume-made DNA-NTs with photonic chips. This integration provides insights of DNA-NTs structural features, both independently and in the presence of interacting molecules.
The comprehensive integration proposed by iSenseDNA is expected to have two significant effects:
-It will contribute to and influence the European and global biotechnology, pharmaceutical, and sensor sectors, thereby elevating technological excellence and expanding the product offerings of EU entities, thereby strengthening their international position.
-It will enhance competitiveness, leading to advancements in the fields and providing substantial socio-economic benefits.