In a series of pioneering works in the early 1970's, John Kosterlitz and David Thouless first connected the concept of topology to the physics of solids. The basis of this framework is the discrete topological unit, an object defined by its resistance to being smoothly deformed into a continuous background, in the way a disk cannot be smoothly deformed into a ring or torus. Kosterlitz and Thouless showed that the most favourable configurations of the systems they explored must host these topological units. They then went on to predict a material phase transition without symmetry breaking based on these objects, violating all known theories and observations at the time. This so-called topological phase transition has subsequently been used to describe transitions in thin-film superconductors, liquid crystals, and two-dimensional magnets. For this work, Kosterlitz and Thouless shared the 2016 Nobel Prize. Yet, despite the groundbreaking nature of these findings and their subsequent wide-ranging experimental support, the topological units originally predicted have never been observed at the single unit level. In this programme of work, we will use highly advanced microscopy techniques to "see" each of these topological objects for the first time. The unparalleled resolution of these microscopes can be further used to map the interior of the objects all the way down to their atomic building blocks. These experiments, when combined with advanced computational approaches to the original problem considered by Kosterlitz and Thouless, will provide an entirely new microscopic portrait of these topologically protected objects. Yet, this work aims far beyond simply observing the topological units; we will develop and deliver a series of approaches to actively manipulate these objects. The first set of techniques for manipulation will utilize influence from the microscope itself, in much the same way a magnifying glass can be used to start a fire. The second series of approaches will modify the surrounding environment to influence the properties and behaviour of the topological objects. As an individual topological unit cannot be smoothly deformed, it represents an unprecedented opportunity for information technology: using a topological state to store and protect a piece of information. Topologically protected data sidesteps the conventional approaches based on energy to protect information, making them extremely promising for high-density, energy efficient approaches to magnetic information technologies. Ultimately, the set of experiments proposed is designed to inform how we might move from a microscopic topological element toward a fully functional unit of a computer. The insights picked up along the way will answer many more fundamental questions: To what extent does topology protect information? How do these units behave in real, that is defective, materials? What approaches can we take to influence the fundamental behaviour of these objects?

Most agricultural products are derived from fruits of flowering plants, such as wheat, rice and corn. Since fruits originate from flowers, crop improvement requires a detailed understanding of flower and fruit development. Research on reference species, such as Antirrhinum or Arabidopsis, has revealed genes that control key steps in the development of flowers and fruits. These genes encode transcription factors, which regulate other genes that contain specific DNA sequences within their regulatory regions. It is believed that variation in these regulatory sequences and in their interaction with key transcription factors have played a major role in creating the changes in flower and fruit development seen during evolution and in plant domestication. We aim to understand how networks of transcription factors and their target regulatory sequences control flower and fruit development, how these networks vary between species, and explore these variations for practical use. We will focus on a key set of regulatory genes, originally identified in Arabidopsis. One of them is WUSCHEL (WUS), which controls the stem cell population that sustains development of all new plant organs. During floral organogenesis, WUS is repressed through the action of AGAMOUS (AG) and SEEDSTICK (STK). AG goes on to play a key role in specifying stamen and carpel identity, while STK guides ovule development. Under the control of AG, a further set of genes controls cell differentiation within the carpels, including the development of structures that in some species eventually allow the fruits to open and release seeds. This network includes SHATTERPROOF (SHP), FRUITFUL (FUL), JAGGED (JAG) and REPLUMLESS (RPL). We will initially use Arabidopsis to fill gaps in our knowledge of how these genes regulate each other and additional target genes during development. Each of the European partners in this project will focus on a subset of the genes mentioned above. In all cases, we will first identify the regulatory sequences that are targeted in vivo by the transcription factors encoded by these genes. We will then verify whether these target sequences are conserved across species and test their importance for the expression of the genes that contain them. We will then check whether variations in regulatory sequences can explain some of the developmental differences seen across species. In our case, we will check whether changes in the regulation of SHP, FUL, JAG and RPL are involved in the differences in fruit development between Arabidopsis and rapeseed. Based on the results, we will then perform a targeted screen for changes in regulatory sequences that may alter rapeseed fruit development for practical use, specifically, to reduce seed loss due to premature opening of the fruit.

Safeguarding insect biodiversity has a global impact. Insects increase crop yields, help food production and economies, and are essential for ecosystem functioning. Scientific research and expertise must, therefore, ensure we not only understand what is causing global insect biodiversity changes but also enable us to mitigate the further consequences for nature and people. Tropical forests are an ideal setting to investigate the occurrence, drivers and consequences of insect biodiversity loss because they are home to much of Earth's terrestrial biodiversity - including the majority of all known species, and provide many ecosystem services upon which humanity relies. Despite the growing number of academic studies and media headlines drawing attention to 'collapses in insect biodiversity', the status of insect populations continues to attract insufficient research attention. This bias is evidenced by the fact that only c. 1% of all described insects have had their conservation status assessed by the IUCN compared with 72% of vertebrates. Our ability to inform better environmental decision-making and conservation policy-making is further limited by other three factors. First, the tropics have been mostly overlooked in previous large-scale and long-term assessments of insect biodiversity trends. Second, little is known about how the use of agricultural pesticides affects tropical insect populations in nearby forests. Finally, our knowledge of insect interaction networks within tropical forests is limited to a few assessments based on single locations or model taxa. As a result, we continue to miss a broader picture of the nature and scale of changes in tropical insects' diversity and populations, the factors driving these changes, and the further consequences for forest function and stability. To redress these gaps in our understanding, my research aims to: 1) investigate the occurrence, scale and causes of changes in tropical insect biodiversity; 2) quantify the impacts of agricultural pesticides and heavy metals on insect populations; 3) determine the cascade effects of insect loss for their interactions with other biological groups; and 4) promote biodiversity conservation through forecasting how distinct scenarios of climate change and land-use intensification will affect tropical insects to inform the decision-making. To achieve this, I will establish the first pantropical insect monitoring programme with standardized methods in Amazonian, African and Asian forests. This information will be combined with state-of-the-art ecotoxicology, metabarcoding, remote sensing and ecological modelling techniques to assess disturbance-driven impacts on insect communities and populations, changes in interaction networks with other taxonomic groups, and the contamination by distinct pollutants. Moreover, I will integrate information generated through the fellowship with large-scale spatialized insect abundance data from the study regions to forecast the impacts of further climate and land-use changes on insect biodiversity. To achieve impact and inform practices and policies, I will engage with distinct stakeholders in the study regions. To the best of my knowledge, this will be the first pantropical study aiming to investigate spatiotemporal changes in multiple insect groups surveyed with standardized methods in tropical forests. In doing so, my research will help us to understand the causes and mitigate the consequences of changes in tropical insect biodiversity; and generate data that will inform policy-making and biodiversity conservation strategies in the hyperdiverse tropics.

Over 200 million children under the age of 5 years in low-resource settings are exposed to adverse environmental factors, such as inadequate nutrition, physical illness and a lack of stimulation. This can have consequences for their ability to achieve important developmental milestones and, as a result, for subsequent school performance. While this is recognised as an important issue, there is very little research that aims to identify the earliest signs of risk and how it shapes development. Identifying early signs of risk in infancy is crucial for developing interventions to help children achieve optimal outcomes. It is also important to better understanding how specific aspects of a child's environment, such as nutrition and caregiving practices, contribute to their development. With this work, we will be better able to understand how certain risk factors impact on development and also how to best promote enriching elements within the family and broader community that can offset the impact of risk. The aim of this research is to investigate the development of cognitive skills from infancy to preschool age among a group of children from a rural region of The Gambia, West Africa. The data for this project comes from the Brain Imaging for Global Health project (BRIGHT; globalfnirs.org), a study that has been following a group of children in The Gambia from the prenatal period to preschool age to measure their brain and cognitive development during early childhood. The specific aims of this study are to: (1) Examine cognitive development from infancy to preschool age among this group of children in the rural Gambian setting. Our goal is to study individual differences in development, which may help to identify children who show delayed development compared with the rest of the group. (2) Investigate whether the ability to regulate attention and respond to social input during infancy predicts cognitive development during preschool age. We will use assessments of behavioural and neural responses to measure these skills in infancy and explore how they relate to outcomes during preschool age. (3) To understand how both adverse and enriching elements of a child's environment contribute to their cognitive development. In particular we are interested in examining how exposure to adversity early in life impacts on development. The adverse factors that we will investigate are poverty, poorer physical growth and maternal mental health difficulties. We are also interested whether enriching factors, including maternal engagement and broader caregiver support, can promote healthy cognitive development and offset some of the impacts of risk. (4) In addition to our research aims, we will also engage members of the Gambian community (parents, healthcare professionals) to ask for their input in our work. Moreover, we will establish a network of researchers from African institutions and across the globe, who study early childhood development in Africa, to share our findings and form collaborations. Our work has the potential to have important impacts for research, as well as the development of interventions. Firstly, this study can help us better understand the general development of children in The Gambia. It can also help identify early signs and risk factors for developmental difficulties. Finally, our findings will help to identify and promote elements of the family and broader community that provide enrichment. With this work, we aim to make a lasting contribution to the research community and society in The Gambia and broader global health settings.

Molecular imaging is one of the key tools for non-invasive clinical diagnosis and opens up the possibility of personalising patient treatment. Positron Emission Tomography (PET) in particular is expanding rapidly and new PET imaging centres are currently being installed across the UK. Biomedical research provides increasing numbers of active molecules that target disease sites in the body and thus could in principle function as imaging agents by labeling with a positron emitting isotope. However, 18-F-FDG is currently the only routinely used PET tracer in the clinic, despite the wide availability of the 18-F radionuclide. This is mainly due to the complexity of the multistep-procedures requiring specialized equipment to make the 18-F labeled imaging agents. The current labeling methods also can be harmful to sensitive biomolecules and thus a small precursor molecule is often labeled that is then attached to an active biomolecule to create the imaging agent. This project will develop a new 18-F-labeling method for sensitive biomolecules which uses the metal aluminium to bind fluoride, rather than carbon-fluorine bond formation which has been the main approach adopted hitherto. The one step labeling procedure will allow clinicians to add the 18-F-fluoride directly into a prepared kit containing the biomolecule in order to prepare the imaging agent. The use of special polymer beads in the labeling has the potential of achieving a higher ratio of labeled to unlabeled precursor than conventional solution methods. This has the advantage of giving better contrast in-vivo and reducing the problems of patient reaction caused by the presence of unlabelled excess biomolecule. The chemistry involved requires no specialised equipment and the faster, kit-based method helps to minimise the exposure of radiation workers to the radionuclide. To achieve our aim, we are designing metal binding sites for fluoride that will allow radiolabeling under conditions that do not harm sensitive biomolecules and proteins. We also propose to combine this approach with methods to attach biomolecules of interest in a way that preserves their ability to reach the target site in the body. Additionally, the compounds we propose are intrinsically fluorescent, so that the potential imaging agents can also be evaluated in living cells using fluorescence microscopy, since PET imaging on its own does not have the resolution necessary to observe the behaviour of the complexes in something as small as a cell. By offering much improved labeling, our new system will facilitate the discovery of new potent biomolecules and facilitate the adoption of Positron Emission Tomography in the clinic without the need for expensive, specialized equipment. A final benefit of the ligand chemistry involved for aluminium is that it also has the potential to be used with other metallic PET radionuclides.