The goals are: 1) to develop a universal laboratory-based 4D X-ray microscope with potentials in the broad field of materials science and beyond; 2) to advance metal research by quantifying local microstructural variations using the new 4D tool and by including the effects hereof in the understanding and modelling of industrially relevant metals. Today, high resolution 4D (x,y,z,time) crystallographic characterization of materials is possible only at large international facilities. This is a serious limitation preventing the common use. The new technique will allow such 4D characterization to be carried out at home laboratories, thereby wide spreading this powerful tool. Whereas current metal research mainly focuses on average properties, local microstructural variations are present in all metals on several length scales, and are often of critical importance for the properties and performance of the metal. In this project, the new technique will be the cornerstone in studies of such variations in three types of metallic materials: 3D printed, multilayered and micrometre-scale metals. Effects of local variations on the subsequent microstructural evolution will be followed during deformation and annealing, i.e. during processes typical for manufacturing, and occurring during in-service operation. Current models largely ignore the presence of local microstructural variations and lack predictive power. Based on the new experimental data, three models operating on different length scales will be improved and combined, namely crystal plasticity finite element, phase field and molecular dynamics models. The main novelty here relates to the full 4D validation of the models, which has not been possible hitherto because of lack of sufficient experimental data. The resulting fundamental understanding of the inherent microstructural variations and the new models are foreseen to be an integral part of the future design of metallic materials for high performance applications.

Herring have been a crucial resource for human communities across the northern hemisphere for time immemorial. In addition to providing cultural and nutritional benefits, these forage fish are a keystone species in their environments, providing myriad ecosystem services including acting as prey for many predators (bears, salmon, seabirds, fish, whales, pinnipeds, etc). In the 20th and 21st centuries, herring populations suffered commercial collapses, culminating in a wave of fisheries closures across the Atlantic and Pacific. The drivers behind these collapses are still debated, with some researchers arguing climate change is to blame and others concluding overfishing caused the population declines. PHANTOM will bring together an interdisciplinary research team to address the question of historical and recent population declines in Pacific herring (Clupea pallasii) in relation to climatic and anthropogenic forcing. To do this, PHANTOM will employ ancient DNA and genomic analysis in conjunction with local traditional knowledge from Indigenous communities in Alaska and Japan. Demographic modeling will be compared to changing climate and management regimes to assess their impacts on this keystone species. PHANTOM will train early-career researcher Lane Atmore in Indigenous- centered research and the development of genetic tools for monitoring and fisheries management to complement her existing expertise in historical ecology and genomic analysis. PHANTOM will culminate with the development of genetic tools and policy advice for Pacific herring management that integrates ancient DNA and local traditional knowledge. The Atlantic and Pacific fishing industries are currently facing challenges due to overfishing and rapid ecosystem change; creating more sustainable management regimes is our best defense against climate change and ensuring food security and economic stability for communities that rely on the sea.

Functional foods containing omega-3 lipids, which have approved health claims by EFSA, have resulted in one of the fastest-growing food product categories in Europe. However, to successfully develop foods enriched with omega-3 PUFA, lipid oxidation of these highly unsaturated fatty acids must be prevented in order to avoid both the loss of nutritional value and the formation of unpleasant off-flavors. Omega-3 PUFA can be added to foods as neat oils or as a “delivery system” such as microencapsulated oil powders and oil-in-water emulsions. Nevertheless, delivery of omega-3 lipids in the form of emulsions reduces the oxidative stability of omega-3 PUFA in some products. Furthermore, microencapsulates are less suitable for liquid or semi-liquid foods than emulsified omega-3 oils due to handling/mixing issues. Therefore, the development of alternative omega-3 PUFA delivery systems, which are easy to disperse and which will lead to improved oxidative stability of omega-3 enriched food products, is urgently required. One of the more promising delivery systems can be functional nano-microstructures obtained by electrospinning technology, which is possible to up-scale. In light of the above, the aim of this research project is to develop advanced omega-3 delivery systems such as electrospun nano-microstructures. To this end, the specific objectives are: 1) Development of physically and oxidatively stable nano-microstructures with omega-3 PUFA and natural antioxidants using electrospinning processing. 2) Production of food enriched with the nano-microstructures having appropriate structural-functional properties and being oxidatively stable. The success of the research proposed will lead to an important advance in the protection of omega-3 PUFA against oxidation when incorporated into food. Thus, the knowledge generated by this study has the potential to being exploited by companies devoted to the production of functional foods containing omega-3 lipids.

Cholesterol transport proteins (CTPs) regulate cellular metabolism, hormone biosynthesis, and organelle contacts, with profound consequences for human health and disease. Despite this, almost no small molecule CTP modulators have been reported, and no methods for determining selectivity across the broader protein class exist. Selective CTP inhibition is conceptually challenging as all CTPs are structurally similar and bind cholesterol. Furthermore, due to redundancy among several CTPs, deciphering the biological roles of their individual cholesterol transport activity has been difficult. ChemBioChol aims to unravel the functions of individual CTPs by developing selective small molecule modulators. Based on seminal work from my lab, I propose employing a sterol-inspired compound design strategy consisting of a primary sterol fragment as “anchor” for CTP binding, fused to secondary natural product fragments to engineer selectivity of the compounds for individual CTPs. My group will develop bio-physical and -chemical tools to determine lipid selectivity of CTPs and optimise selective molecules against them. Preliminary data on the Aster CTP family provides a proof-of-principle that selective and potent chemical tools are attainable, and that the concept is applicable to further CTP families. To determine cellular selectivity of CTP inhibitors against all cholesterol-binding proteins, I will also develop a mass spectrometry-based chemical proteomic approach with a universal cholesterol probe. Optimised CTP inhibitors will be used to determine how CTPs mediate lipid metabolism and trafficking, and their effect on sterol-mediated processes including mTOR signaling and autophagy, with potential applications in neurodegenerative disorders and cancer. A general approach for selectively modulating CTPs is ground-breaking and will have impact beyond this set of proteins by providing a blueprint for studying and targeting other families of lipid-binding proteins in the future.

Water contamination caused by human and industrial activities is a significant global concern. One of the most prominent pollutants is oily wastewater, severely impacting groundwater and drinking water quality. Biocatalysts, such as Thermomyces lanuginosus lipase (TLL), are used in many household detergents to remove lipids effectively. However, their limited solubility and reusability can increase running costs and hinder large-scale applications. To address this issue, we plan to immobilize TLL on solid supports and determine the appropriate surface density of enzymes, conformational changes during immobilization, and the effect of support on its kinetic properties. Our goal is to develop innovative methods for nanoscale imaging of enzymes using transmission electron microscopy (TEM) to gain insights into the structural aspects of immobilization. By investigating the interaction of the immobilized enzyme with the support nanostructure and the lipid substrate, we expect to identify the attributes that maximize the biocatalytic reaction rate. We will explore different immobilization methods on various nanostructures and investigate how TLL interacts with the immobilization matrices at the nanoscale level. Additionally, we will apply water vapor atmosphere in the TEM to explore in situ the dynamic switching between the active and idle state of the single enzyme molecules in real-time by their conformational changes. We are aiming to obtain groundbreaking results and a paradigm shift, based on the in situ kinetic studies of lipase-catalyzed chemical reactions which can become a gateway into the quantum mechanical world of molecular science.