In this proposal, chiral active granular matter (CHIAGRAM) is designed and investigated through a combination of numerical, experimental, and theoretical studies. Granular particles are characterized by collisions that dissipate energy and have been recently “activated” by breaking the translational symmetry of their shapes or internal components. The novelty of this proposal lies in the introduction of chirality through the breaking of the rotational symmetry. The resulting CHIAGRAM will be characterized by a broad range of fascinating single-particle and collective phenomena, such as circular motion, clustering, hyperuniformity, and spatial velocity correlations, whose properties will be systematically investigated through experiments and theoretical models. The implementation of an airflow mechanism and the behaviour of CHIAGRAM under flow will represent an intriguing forward research step in the field of (active) granular systems and, more generally, active matter. Emergent properties, such as negative mobility, odd diffusivity, as well as long-range collective phenomena, are expected because of the interplay between airflow and chirality. The project will fundamentally benefit from the expertise of my supervisor, a world-leading and pioneering scientist in the field of (chiral) active matter, as well as from the experimental and theoretical support provided by the secondment host, a world-leading expert in (active) granular systems. CHIAGRAM will distinguish for originality, proposing a novel granular material with fascinating properties that will open a new research line of experimental and theoretical investigation bridging active chirality and granular matter.

Viruses cause epidemics on all major crops of agronomic importance, representing a serious threat to agriculture and global food security. Among plant viruses, those induced by RNA are of particular concern due to their overrepresentation and the lack of effective countermeasures. As obligate intracellular parasites, their control still relies on an excessive application of pesticides against virus vectors and preventive actions consisting mainly in the detection and removal of infected plants. Virus‐resistant crop varieties are a powerful alternative but often confined to narrow germplasm base and takes long periods to introgress the resistance trait. One of the most effective and sustainable ways to avoid virus infection is to use genome editing to expand genetic tools. Therefore, plant virologists are turning their interests toward host factors that play essential roles in infection as novel antiviral targets. Cell-to-cell movement is critical for virus spread, and thus an ideal point for creating resistance. Plant viruses can exploit plasmodesmata (PD) -channels that interconnect every single plant cell- using encoded so-called movement proteins (MPs) which mediate the transport of the viral genomes cell-to-cell. Understanding the intercellular transport of viruses and the components involved offer breeding targets for genome editing to control virus spread and, thus block viral infection. Therefore, we propose here to identity comprehensively the compendium of MP-interacting proteins using high-end proteomics. Additionally, we will apply the state-of-the-art technology genome editing and advanced microscopy to define the role of MP-interacting proteins during virus transport and infection, laying the basis for novel biotech solutions in agriculture.

The endosymbiotic integration of cyanobacteria within Eukaryotes was one of the pivotal evolutionary transitions. This transition, however, is difficult to study because modern plastids represent highly derived ‘end-states’ and are not transitionary; we know, therefore, very little about the mechanisms involved. Primary plastid endosymbiosis has occurred only twice: once in the ancestor of Archaeplastida and once independently in the amoeba Paulinella. Each Paulinella cell houses two chromatophores, which are photosynthetic units that resemble plastids yet are more closely related to cyanobacteria. Genetic studies of Paulinella and its cyanobacterial-derived chromatophores revealed it is an intermediary in the evolution of a photosynthetic organelle. Studying Paulinella, therefore, offers unique insight into the mechanistic processes of plastid integration. Despite our growing genetic knowledge, little is known about the integration of the chromatophores in terms of their cellular physiology. In this proposal, I aim to address this by exploring this unique association at the metabolomic, transcriptomic and proteomic levels. First, I plan to characterise the metabolites exchanged between the cell and chromatophores using an isotope-labelling metabolic experiment (objective 1). Second, I will study the coordinated light response of the nucleus and chromatophore at the transcriptional, metabolic, and protein level (objective 2). Finally, I will perform a long-term evolution experiment to expose Paulinella chromatophora to high and fluctuating light regimes to test whether its light regulation can evolve in response to different light environments (objective 3). The outcomes will provide insight into the molecular mechanisms that facilitate the integration of the chromatophores within Paulinella. This in turn will aid our understanding of the acquisition and integration of plastids, and the evolutionary trajectory from endosymbiont to organelle.

This project uses integrated history and philosophy for medicine to inform medical practice today. The evaluation of medical tests is today in a state of confusion. Traditionally, the main index used to evaluate diagnostic tests is diagnostic accuracy. Typically, this is done by evaluating the sensitivity (the proportion of patients with a disease that test positive) and the specificity (the proportion of patients without a disease who test negative) of a test. Sensitivity and specificity are commonly assumed to be constants, or to vary only in a limited rage of circumstances. In contrast to this, others claim that sensitivity and specificity are highly variable, so much so that the ‘diagnostic accuracy paradigm’ should be abandoned. Instead of focusing on diagnostic accuracy, some recommend that test evaluation should focus on patient outcomes, whilst others strongly disagree. This confusion is detrimental to medical practice, as it leaves medicine in a state of not knowing how to tell if a medical test is a good one. This project seeks to understand and address this confusion using historical and philosophical tools. Philosophical analysis reveals that the differing attitudes to test evaluation have at their root differing philosophical assumptions about how homogeneous or heterogeneous patients with the same disease are. The project provides and intellectual and social history that traces the development of test evaluation over the twentieth century. It follows how successive generations of researchers have balanced assumptions of homogeneity and heterogeneity and modified them for use in their particular setting. The central claim of this project is that understanding medical history is key to balancing assumptions of homogeneity and heterogeneity skillfully.