In several regenerating organisms it has been observed that distally amputated structures grow slower than proximally amputated ones, resulting in an overall time of regeneration that is independent of the tissue to be reformed. This observation suggests that cell proliferation or cell size could be adjusted with the plane of amputation along the proximo-distal (PD) axis, leading to an interesting scaling behaviour. It has been proposed that positional identity in the limb may be encoded as a proximal-to-distal gradient of cell surface molecules, that would in turn alter intercellular adhesions. Thus, it is possible that such differential adhesions are associated to the control of cell growth during regeneration. The central aim of this proposal is to address this question by combining cell biology, mathematical and physical tools, with the ultimate goal of understanding how the biomechanical properties of tissues affect regeneration, which may have important implications for the design of biomaterials aimed at being used for regenerative medicine. We will tackle this question in the highly regenerative salamander species Axolotl mexicanum, in which limb regeneration is initiated regardless of the amputation plane, and the regenerating limb grows until its size matches the contralateral undamaged one. We will evaluate growth rate and cell cycle of regenerating limbs amputated at different levels, and mathematically describe cell proliferation patterns. We will characterize several cell surface and extracellular matrix molecules along the PD axis, and measure tissue mechanics in vivo. Furthermore, we will for the first time, evaluate the Hippo pathway in salamanders, an important modulator of cell growth in response to several physical inputs, as the causal link between increased tissue stiffness and decreased proliferation.

Implanted electrode arrays are a key component of neuroprosthetic systems designed to restore functions lost through injury or degeneration of the nervous system. Electrode arrays currently used in clinical practice are made from metals (e.g., Platinum, PtIr alloys) encapsulated in silicone. These materials strike a compromise between electrical properties on one side and good tissue integration on the other. For example, the limited charge injection capacity and high mechanical stiffens of metal electrodes is implicated in challenges with long-term stability, mechanical failure, formation of a glial scar and electrode miniaturization. In the COATARRAY project we will develop a specialized coating designed to radically improve the electrical and mechanical performance of electrode arrays. The coating is based on a bioinspired hydrogel material further endowed with electrical conductivity via incorporation of conductive polymers. The coating can be assembled on a variety of ready-made electrode arrays designed for different applications. In this project we will conduct a thorough electrical characterization of the coating as well as mechanical, insertion, sterilisation, cytocompatibility and accelerated ageing tests. In combination with analysis of the regulatory and commercial landscape, this project will establish an essential milestone towards clinical translation of the COATARRAY technology. If successful, our approach to improving the performance of implanted electrode arrays can lead to better clinical outcomes for established neuroprosthetic systems (cochlear implants, deep brain and spinal cord stimulation) but also to the development of promising new treatments.

Recent breakthroughs in the field of genome editing provide a genuine opportunity to establish innovative approaches to repair DNA mutations to replace, engineer or regenerate malfunctioning cells in vitro or in vivo. However, most of the recently developed technologies introduce double-strand DNA breaks at a target locus as the first step to gene correction. These breaks are subsequently repaired by one of the cell intrinsic DNA repair pathways, typically inducing an abundance of insertions and deletions (indels). Ideally, for many applications genome editing should, however, be efficient and specific, without the introduction of indels. Site-specific recombinases (SSRs) allow precise genome editing without triggering endogenous DNA repair pathways and possess the unique ability to fulfill both cleavage and immediate resealing of the processed DNA in vivo. However, customizing the DNA binding specificity of SSRs is not straightforward. With this project, we propose to solve this shortcoming. We have already demonstrated that by applying substrate-linked directed evolution, SSRs can be generated that specifically recognize therapeutic targets. The objective of this project is the development of a universal genome editing platform that allows flexible, efficient and safe gene corrections in cells of any origin without triggering cell intrinsic DNA repair. GenSurge aims to: i) sequence an unprecedented, comprehensive compendium of evolved SSRs to understand the directed molecular evolution process at nucleotide resolution; ii) integrate the knowledge obtained in i) to develop a unique SSR-based approach to correct genomic inversions; iii) develop a universal SSR-based strategy that allows flawless, precise and safe genome editing to correct any gene defect in human, animal or plant cells. The successful implementation of this project will deliver a comprehensive, safe and efficient platform from which genome surgery-based cure strategies can be initiated.

The 3P-EL project focuses on developing a three-phase electrolyser which represents a groundbreaking innovation in hydrogen production technology. By overcoming the fundamental limitations of traditional methods, it provides a more sustainable, cost-effective, and energy-efficient solution. The invention’s scalability and compatibility with renewable energy sources position it as a transformative tool in advancing the global transition to a hydrogen-based green energy economy, enhancing its competitiveness with other energy sources. We aim to develop a novel reactor concept with the potential to achieve significantly higher energy efficiency compared to existing designs. At its core, the three-phase electrolyser features a new electrode configuration. Furthermore, by stabilizing the electrochemical environment and minimizing overpotential stress, the catalyst’s lifespan is significantly extended, reducing maintenance costs. The improved efficiency and durability of the system make it highly suitable for large-scale applications, promoting hydrogen as a future green chemical resource and energy carrier. Preliminary lab-scale tests have revealed highly promising prospects, demonstrating the system’s ability to achieve approximately 20% lower energy consumption in hydrogen production. These early results indicate strong potential for scaling up the technology, reinforcing its viability for industrial applications. If successfully developed, this advancement could significantly propel green hydrogen production, reduce energy consumption and operational costs, and accelerate the adoption of clean energy technologies.