ERC FUNDED PROJECTS

Diabetes, stroke and coronary artery disease (cardiometabolic diseases) are the leading cause of death in Europe. Given that effective pharmacological and lifestyle interventions are available, it is important to identify high risk individuals at an early stage. Traditionally, this is done using clinical prediction models. However, the established models have substantial limitations: they are often used by doctors only when an underlying disease is already suspected, they are not developed on updated nationally-representative data and they require time-consuming clinical measurements. Thus, a substantial part of the population is not provided with risk assessment. I propose to revolutionize the existing approaches to primary prevention by providing risk assessment of cardiometabolic diseases before an individual even steps into the doctor’s office for a visit. To this end my project has three main objectives: 1) Development of artificial intelligence (AI) approaches to model health trajectories based on nationwide registry data on medications, diagnoses, familial risk and socio-demographic information to obtain accurate risk estimates for cardiometabolic disease. I will integrate high quality data from selected countries that have long traditions of registry data (Finland and Sweden, over 7.5 million individuals). 2) To identify health trajectories that maximize the clinical utility of genetic scores by integrating genetic and registry-based data on > 1 million people to identify subgroups of individuals for whom genetic information might improve risk prediction. 3) Validation of AI and genetic-based risk assessment as first-stage screening via a clinical study in 2800 individuals. My project leverages the latest developments in AI and high-quality data of unprecedented scale to deliver a paradigm shift with important public health consequences by potentially changing the way cardiometabolic disease risk is assessed.

1 550 057 €

Start date: 2021-01-01, End date: 2025-12-31

The Anthropocene, the current geological epoch, is characterised by human-induced ecological changes, which have prompted a global biodiversity crisis. Human-introduced alien plants could help to offset native species loss, augmenting diversity and maintaining the services and capital that humans derive from nature. However, alien species that become invasive are themselves a key threat to biodiversity. Alien species thus presents a huge challenge for biodiversity conservation in the Anthropocene: should their arrival and establishment be inhibited or disregarded as they can potentially both exacerbate and ameliorate biodiversity loss? Coupling empirical and theoretical approaches, ALIENIMPACTS will directly address this challenge by developing an approach for accurately predicting impacts of alien plant invasions on plant community diversity and identifying the circumstances under which negative impacts will occur. Using temperate grasslands as a model system, ALIENIMPACTS will use innovative field experiments and global observations to systematically quantify – for the first time – how often, for how long, to what extent, under what conditions and in what ways alien plants can impact plant community diversity. ALIENIMPACTS will develop mechanistic niche models, validated with empirical data from grasslands in North America, Europe and Australia, that will enable realistic scenarios of invasion biodiversity impacts to be forecast, now and in the future. Developing empirically accurate mechanistic models that predict invasions and their biodiversity impact is a highly ambitious goal. Its achievement will mark a step-change in ecological theory and understanding, will inform environmental policy and management, and address a critical research challenge of the Anthropocene: how to conserve the biodiversity of plants – the dominant life form on earth – under global environmental change.

1 999 997 €

Start date: 2021-04-01, End date: 2026-03-31

The hippocampus is critical for the storage of episodic memories and has been extensively studied on its role in spatial memory. The hippocampus is also a central model for in vitro studies on the molecular, cellular and microcircuit basis for learning and memory. I propose to use a new technology that I developed to record and manipulate the membrane potential of multiple neurons, simultaneously, in behaving animals to reveal the mechanisms by which hippocampal circuits process spatial information. This research will bridge the gap between the in vitro mechanistic studies and the in vivo efforts to describe the spatial representations. I first propose to employ the voltage imaging technology for detailed mechanistic studies of the function and plasticity of hippocampal microcircuits during place cell formation (Objective 1). To this end, we will combine voltage imaging with Optogenetics in head-fixed mice performing virtual navigation in familiar and novel environments. To expand to a ‘systems’ view on hippocampal plasticity, we will next establish a method for optical selection of single neurons based on their functional profile (Objective 2). We will use this technology to trace the long-range projections and the pre- and postsynaptic landscape of photo-selected CA1 neurons. In the last objective, we will combine both technologies to dissect the contribution of different entorhinal cell types (i.e. grid cells, border cells, and speed cells) to place cell formation in CA1 (objective 3). To this end, we will image the entorhinal cortex and photo-select cells based on their functional profiles. We will then image CA1 while manipulating the activity of the selected entorhinal cells. Our work will provide new discoveries on the mechanistic basis for spatial memory and will comprise a first step towards broader understanding of how the brain stores and retrieves episodic memories.

1 486 797 €

Start date: 2020-12-01, End date: 2025-11-30

Aphids are devastating insect pests of crops globally, and pose a major threat to food security. Crucially, there is a lack of durable genetic crop resistance against aphids, and current control relies almost exclusively on insecticides, which are costly and damaging to the environment and to which aphids develop resistance. These insects deliver proteins inside host plants, called effectors, to suppress the plant immune system and enhance susceptibility. I recently discovered that these effectors exhibit their activity via interacting with host plant proteins pointing to important conceptual parallels between plant-insect and plant-microbe interactions. This raises important new questions that urgently need to be addressed to enable development of novel protection strategies against aphids that are durable and sustainable. These are: What is the mechanistic and structural basis of aphid effector-triggered susceptibility? How can we interfere with aphid effector-triggered susceptibility? APHIDTRAP will address these questions using an innovative strategy: 1) I will introduce a structural biology approach to the insect effector biology field to reveal protein 3D structures of aphid effectors and their host protein targets in bound and unbound state, and determine how mutations in these proteins affect interactions and protein functions. 2) I will use both natural variants and mutants of effectors and host protein targets, combined with in planta functional assays to explore plant-aphid molecular co-evolution. 3) I will identify host protein target interactomes and investigate how mutations affect network functionality. 4) I will use information generated in 1-3 to develop and apply a synthetic biology approach to prevent aphid effector-triggered susceptibility in potato crop plants. APHIDTRAP’s vision is to elucidate the mechanisms that underlie susceptibility to aphids and investigate how we can interfere with these to reduce crop susceptibility to insect pests.

1 999 992 €

Start date: 2021-06-01, End date: 2026-05-31