Despite the fact that vaccine use in poultry is greater than in any other farmed species, the mechanisms by which they induce protection, particularly at mucosal surfaces, are poorly understood. Many diseases constraining avian productivity and welfare affect the respiratory tract and are multi-factorial. A better understanding of responses in the respiratory tract to bacterial and viral infections, co-infections and vaccines is needed to control endemic production diseases. Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease, threatening food security and avian welfare at a time of increasing global demand. Infections frequently involve sepsis, inflammation of visceral organs and reduced egg yield/quality, with losses through early mortality, reduced productivity and product condemnation. The expansion of free-range production systems will increase the incidence of colibacillosis through greater exposure of birds to environmental pathogens, stress and injury associated with forming a social hierarchy. Importantly, APEC infections are frequently associated with respiratory viral infections. The nature and consequences of host-pathogen interactions during APEC (co-)infections are poorly understood. Virulence factors of APEC, antagonistic or synergistic effects of co-infection and the basis of immunity and resistance are ill-defined. The EC-wide ban on prophylactic antibiotic use and transmissible resistance render poultry susceptible to APEC infection. Existing vaccines confer limited serogroup-specific protection. This project will advance understanding of mucosal immune responses in the avian respiratory tract. It will provide a comprehensive description of the respiratory tract immune system, leading to new tools to study immune responses and improved understanding of the mechanism and site of antigen presentation in the lung. We will thereby identify correlates of resistance and susceptibility to, and the impact of viral infections on the outcome of, APEC infection. Using transgenic chickens we will further characterise the role of antigen-presenting cells and humoral immunity during APEC infection and vaccination, for example by using our unique MacRed chickens (in which all cells of the mononuclear phagocyte lineage (macrophages, monocytes and dendritic cells) express a fluorescent protein driven by the chicken CSF-1 receptor), and immunoglobulin knock-out chickens (which lack the B cell receptor and thus antibody).

The SUNCOCAT proposal aims at the nanoscale engineering of electron and energy transfer pathways and ultimately, the development of efficient biophotoelectrodes, to capture solar light and convert CO2 to carbon monoxide, the latter product being an important platform chemical and fuel. This novel class of the hybrid photoelectrodes will employ the strong reducing power of photosystem I (PSI) to drive the high performance of the CO2 converting biocatalyst, CO dehydrogenase (CODH). A robust extremophilic PSI will serve as the central light harvesting and charge separating biocatalyst, capable of capturing solar energy in the visible part of the solar spectrum to drive reductive chemistry. Photoactivated electrons generated by PSI upon visible light capture will be wired to novel O2-tolerant CODH variants for conversion of atmospheric CO2 into CO. The well-structured and oriented attachment of the PSI-CODH hybrids to the electrode surface via the DNA building blocks is the breakthrough approach of this proposal for enhanced solar energy capture and conversion into fuel. To achieve the highest possible energy conversion efficiency, SUNCOCAT uses a highly interdisciplinary approach based on both fundamental electrochemical investigation and quantum mechanical/molecular mechanics (QM/MM) modelling of electron transfer (ET) together with a number of physico-chemical, genetic, and biophysical methods in order to efficiently interface the abiotic and biotic components for solar-driven reduction of CO2 to CO, aiming at high product selectivity and yield. Rational assembly of the robust biophotocatalytic assemblies onto the electrode surface with the use of advanced physico-chemical methods (molecular wiring, DNA origami technique and plasmonic enhancement of absorption and fluorescence), as well as oriented coupling of the hybrids to earth-abundant conductive materials, i.e., single layer graphene (SLG) on fluorine-doped tin oxide (FTO), will be used to optimise the energy and charge transfer (CT) within the hybrid photoelectrode for efficient solar-driven chemical conversion. With its multifaceted and interdisciplinary approach, SUNCOCAT strives for highly efficient solar-to-fuel system based on novel hybrid nanoassemblies to drive the desired reductive chemistry via a rational approach based on a combination of iterative ET modelling and state-of-the-art spectroelectrochemical investigation of ET and its competing pathways