The insulin-linked polymorphic region (ILPR) resides in the promoter region of the gene coding for insulin (INS). This region consists of a 14-base pair tandem repeat DNA sequence of 5'-ACAGGGGTGTGGGG-3'/3'-TGTCCCCACACCCC-5' and is located 363 base pairs upstream of the transcription start site of insulin. The insulin-linked polymorphic region can form non-canonical DNA secondary structures such as G-quadruplexes, i-motifs and hairpins. Previous work at the UCL School of Pharmacy has shown that different native insulin-linked polymorphic region sequence variants form different DNA structures and these result in differences in insulin gene transcription. This project aims to reveal insights into the relationship between different DNA sequences in the insulin promoter region, the types of non-canonical structures they form, transcription of insulin and how this is influenced by small molecule ligands. The project will use biophysical approaches to determine the structure of different sequences in the insulin promoter, cell and molecular biology to understand the effects of different sequences and structures on insulin expression, including using small molecule ligands as probes. Finally, computational biology and x-ray crystallography will be used to design improved compounds that target the insulin-linked polymorphic region and switch on insulin transcription using structure-based rational design.

Terahertz (THz) communication is an up-and-coming candidate technology for 6G, aiming to meet the stringent performance requirements of next-generation communications, such as hyper rates on the order of terabits-per-second. However, a notable challenge in THz communications is the increased path losses. Fortunately, extremely large-scale multiple-input multiple-output (XL-MIMO) technology can effectively compensate for this issue. The combined implementation of THz and XL-MIMO, offering extensive spatial degrees of freedom and ultra-wideband capabilities, has emerged as a crucial technology for high-precision target sensing and high-throughput communications, effectively meeting the needs of integrated sensing and communication (ISAC). However, the large antenna aperture of XL-MIMO will make near-field communications dominant. On the other hand, the ultra-wideband nature of THz signals will introduce the beam-split effect. There is an urgent need to consider these unique characteristics to synergize artificial intelligence (AI) with XL-MIMO for developing THz communication and sensing. This proposal aims to design AI-native XL-MIMO THz communication by developing novel techniques: 1) Intelligent THz XL-MIMO Communication Design. Developing low-complexity, learning-aided channel estimation methods for XL-MIMO communication systems while studying intelligent precoding to manage hybrid field interference for mixed near-field and far-field communication users. 2) Hybrid-Field THz XL-MIMO ISAC Design. Developing ISAC precoder for target sensing and electromagnetic property sensing, while developing a network-level ISAC performance analysis framework. 3) Practical implementation of Intelligent THz XL-MIMO ISAC. Developing resilient AI-native XL-MIMO ISAC using generative diffusion model and intelligent XL-MIMO ISAC testbed. The main research approaches include electromagnetic wave theory, nonlinear optimization, and reinforcement learning, etc.

The increasing frequency and severity of multi-hazard events necessitate comprehensive frameworks to assess the compounding risks to infrastructure systems. Multi-hazard risks, particularly from independent hazards impacting the same infrastructure and communities simultaneously (or close in time), significantly affect the resilience of urban centers. Recent events, such as the flooding in Türkiye following the 2023 earthquake, demonstrate the compounded impacts on communities and infrastructure. These interactions are understudied despite their severity, particularly concerning infrastructure resilience and recovery. To address this gap, the RE-EnForce project introduces a novel computational framework to quantify multi-hazard risks in interconnected infrastructure systems, focusing on interactions between unrelated hazards that impact the same system. The project will also provide novel risk and resilience metrics for stakeholders, including government agencies, emergency managers, and the reinsurance industry. While adaptable to various infrastructure systems and hazard interactions, RE-EnForce prioritizes models to assess the risk and resilience of reinforced concrete building portfolios and transportation networks, accounting for impacts of earthquakes and floods occurring in the same region and within short timeframes. The key project outcomes include (a) consistent consequence scales to evaluate the functionality of individual RC buildings and building portfolios for hazard interactions, (b) similar scales to assess the functionality of bridges and transportation networks, and (c) a decision-making framework considering the system-level performance of interconnected infrastructure. By addressing the compounded effects of spatial and temporal hazard interactions, RE-EnForce advances multi-hazard risk assessment and offers a holistic approach to disaster risk reduction. It supports risk-informed decisions and aligns with global efforts towards urban resilience.

The BioMedical Research and Innovation (R&I) sector is characterised by specific challenges, emphasising the need for intersectional gender equality interventions with the potential to benefit health and wellbeing in society. The INCLUDE project drives institutional change towards gender equality and inclusiveness by co-designing, implementing, and evaluating innovative measures to advance Gender Equality Plans (GEPs) within seven public BioMedical Research Performing Organisations (RPOs) and one private Research and Technology Organization (RTO) using intersectional and intersectoral approaches. A geographically inclusive consortium covers 2 EU Member States and 6 Widening countries, in Northern, Eastern, Southern, and Western Europe, with more and less advanced policy frameworks. INCLUDE conducts a comprehensive analysis of GEPs and data collection practices already in place, identifying areas for improvement and potential challenges. The analysis, alongside a mapping of good practices and tools, and the identification of the competencies and learning needs of implementing partners, will inform the co-design of inclusive GEP pilot actions to improve intersectional gender equality. Substantial operationalization of intersectionality is enshrined in the consortium composition comprising scholars and activists who possess significant knowledge, expertise, and specialised tools for implementing an intersectional approach. Tailored training programs and collaborative learning initiatives, the establishment of thematic hubs, a mentoring scheme, and study visits will ensure that internal capacities are fostered, and knowledge sharing is promoted. INCLUDE places emphasis on the long-term sustainability of an intersectional approach to GEPs through the elaboration of detailed sustainability plans and the strengthening of partnerships with the local innovation ecosystems, while promoting and multiplying networking efforts through the INCLUDE toolkit, CoP and Manifesto.

Recent pandemics showed Europe how serious health threats can be to society. Proactive approaches are needed to ensure that medical countermeasures are available during pandemics. PROACT EU-Response’s overarching objective is to prepare Europe for future pandemics by strengthening upon existing networks of experts and civil society focused on clinical therapeutic platform trials within hospital inpatient settings across Europe. In case of an outbreak, this network will provide capacity to pivot rapidly to implement large, multi-country platform trials studying therapeutics and diagnostic-tool performance. Underpinned by strong community involvement and further strengthened by the inclusion of social and implementation scientists, PROACT EU-Response centres on six objectives: expand a solid network of clinical centres across Europe that will implement a clinical trial assessing a syndromic approach for respiratory viral infections; strengthen a laboratory network to identify pathogens and biomarkers of disease monitoring for routine surveillance; support a network of methodologists and trialists who will ensure the trials’ logistical and methodological aspects; initiate a network of professionals to work on preparedness tools to ensure a smooth pivot from inter-pandemic to the pandemic period in case of an outbreak; build a network of social science researchers who will provide nuanced understanding of the social contexts; and establish a community group to work on activities that will empower patients and citizens in Europe regarding their own health and educate them about science and health issues. By bringing together scientists, social science researchers, and civil society members, PROACT EU-Response will benefit the entire European population and beyond through decreased mortality and morbidity associated with emerging diseases, lower societal economic costs of morbidity, strengthened research and innovation expertise, human capacities, and know-how for combatting communicable diseases.