Lung disease is the third biggest cause of deaths globally. For the irreversible and terminal lung disease patients, lung transplantation is the only long-term therapy. Due to the unavailability the suitable donors, there is not only a minimum of 18 months of wait on the organ donation. Patients who eventually secure a lung transplant have less than 20% chance of recovery due to ‘poor organ function’. Therefore, there is not only a great need for an artificial lung as a permanent replacement organ but also as a bridge to transplantation. Existing artificial lung devices fail to mimic the flow gas exchange properties of a human lung and suffer from low biocompatibility, leading to undesired blood coagulation and hemolysis which limits their applicability to up to 30 days. The complexity and risk associated with current artificial lung technologies mean that they are not offered as long-term lung replacements or as a suitable bridge to transplantation. Through this 36 months EIC pathfinder project, the consortium led by Smart Reactors Ireland, aims to develop the world’s first biobased nanomaterial ‘nanocellulose’ to manufacture an artificial lung device used as a bridge to lung transplantation. The consortium will develop an initial proof of concept nanocellulose device to demonstrate gas transfer and initial hemocompatibility in blood. The proposed approach is expected to have two benefits, the first is that blood flow can occur in laminar flow conditions reducing haemolysis and damage to the blood. Secondly, nanocellulose, has the potential to be endothelialized which would allow for long term gas exchange without the need for systemic anticoagulants.

PANDORA (Probing safety of nano-objects by defining immune responses of environmental organisms) shall assess the global impact of engineered nanoparticles (NP) on the immune responses of representative organisms covering all evolutionary stages and hierarchical levels from plants to invertebrates and vertebrates. Immunity is a major determinant of the survival and fitness of all living organisms, therefore immunosafety of engineered NP is a key element of environmental nanosafety. PANDORA will tackle the issue of global immunological nanosafety by comparing the impact of widely-used NP (e.g., iron, titanium and cerium oxide) on the human immune response with their effects in representative terrestrial and marine organisms. This comparison will focus on the conserved system of innate immunity/stress response/inflammation, aiming to identify common mechanisms and markers across immune defence evolution shared by plants (Arabidopsis), invertebrate (bivalves, echinoderms, earthworms), and vertebrate (human) species. PANDORA’s objectives are: 1. To identify immunological mechanisms triggered by nano-objects, and predictive markers of risk vs. safety; 2. To do so by a collaborative cross-species comparison, from plants to human, of innate immune defence capacity, using selected, industrially-relevant NP; 3. To design predictive in vitro assays to measure the immuno-risk of NP to the environment and human health, as new approaches to industrial and environmental nanosafety testing. PANDORA will train 11 PhD students in an overarching training programme involving training-by-research, joint courses of technical, scientific and transferrable skills, participation to public scientific events, and an intense intersectoral networking exchange plan. The PANDORA consortium encompasses academic institutions, research centres, and SMEs, all with proven experience in higher education and training, and state-of-the art scientific and technical expertise and infrastructures.

Negamycin, a specialized metabolite of the hydrazine family, is produced by the actinobacterium Kitasatospora purpeofusca. In addition, two metabolites of the negamycin family, 3-epi-deoxynegamycin (3-Dneg) and leucyl-3-epi-deoxynegamycin (L-3-Dneg) produced by the actinobacterium Streptomyces goshikiensis, have been identified. Negamycin metabolites are pseudopeptides with hydroxy-ß-lysine as the central amino acid. Negamycin (but not 3-Dneg and L-3-Dneg) possesses antibacterial activity, especially against bacteria from the ESKAPE list (Klebsiella pneumonia, Enterobacter sp. and Pseudomonas aeruginosa), for which new antibiotics are urgently needed. Its mode of action is based on binding to ribosomes via a novel mechanism, stimulating miscoding and inhibiting ribosome translocation. Moreover, like 3-Dneg and L-3-Dneg, it possesses stop-codon readthrough activity. Negamycin metabolites could therefore be used for the treatment of genetic diseases caused by mutations leading to in-frame stop codons (e.g. some forms of the Duchenne muscular dystrophy or cystic fibrosis). In this project, we aim to (i) identify the genes involve the biosynthesis of the metabolites of the negamycin family, (ii) elucidate the function of the encoded enzymes (iii) increase the production of negamycin metabolites in order to isolate quantities sufficient for biological studies and, (v) further investigate the antibacterial and readthrough activities of negamycin and its analogues toward nonsense mutations.