The transcription of almost all genes occurs via random transitions between active and inactive gene states. The net mRNA production is determined by the frequency and size of the resulting random bursts of mRNA synthesis, making gene expression a stochastic process. As a consequence, responses of individual immune cells upon bacterial infection are highly variable, resulting in different infection outcomes. For example, only a subset of innate immune macrophages may accurately recognize and kill invading bacteria. In this project, using mathematical modelling of transcriptional bursting, inference of single-cell genomics and live-cell imaging data, I aim to understand mechanisms involved in coordination of the innate immune responses to pathogen stimulation. In particular, I will study how the foodborne Listeria monocytogenes manipulates the host cell’s gene expression and signalling responses in order to establish a successful infection. I hypothesise that modulation of transcriptional bursting characteristics is a key control mechanism that allows the host to fine-tune its response to pathogen infection, and in turn enables the pathogen to implement its infection strategy. Mechanistic understanding of transcriptional dynamics induced by bacterial infection will inform strategies to improve infection outcomes in the future.
Context: Diarrhoeal diseases result in approximately 1.8 million deaths each year worldwide, in many cases due to a lack of access to clean water. Current analytical technologies to assess water quality in low and middle income countries are limited in terms of technical performance (e.g. sensitivity, speed and specificity) and suitability (e.g. cost, sustainability, and integration with local and national context). We have recently worked with the Department of Water Resources (DWR) in Vanuatu to co-develop the specifications of next generation water quality monitoring technology that addresses these limitations. This studentship will investigate such analytical technology based on real-time detection of DNA amplification using low-cost field effect transistor sensors. Aims and Objectives: This project will demonstrate an electronic water quality sensor array that can be readily manufactured and deployed in Vanuatu and that is able to rapidly detect and quantify a panel of molecular targets that are indicators of faecal contamination. 1. Understand relationship between the structure and composition of IrOx electrodeposited on a printed circuit board (PCB) electrode and its pH sensitivity and stability 2. Demonstrate a PCB ion sensitive field effect transistor (PCB- ISFET) optimised for stability, reproducibility and pH sensitivity (aiming for better than 0.1 pH). 3. Fabricate PCB-ISFET for label-free detection and quantification of DNA amplification and evaluate in-lab aiming for <10 CFU/100mL in < 2 hours. Research Methodology: Research will focus on quantification of E. coli. We will use known primers for E. coli and, using a laboratory PCR system, optimise a loop-mediated isothermal amplification (LAMP) protocol focusing on sensitivity to buffer and contaminants, temperature and assay speed. In parallel, we will investigate the fabrication of PCB-ISFETs and associated drive circuitry. We will use standard PCB fabrication of copper-clad FR4, which can be replicated or made available in Vanuatu and develop the analogue front-end, including ISFET bias circuitry and signal conditioning. The performance of the ISFET is dependent on the pH sensitivity, stability and reproducibility of the IrOx layer. We will apply a range of analytical tools (electron and atomic force microscopy and x-ray photoelectron spectroscopy) to characterise and optimise IrOx deposition for use in extended gate, PCB-ISFETs. The pH sensitivity will be assessed electrochemically through measurements of the open circuit potential and CV. The optimised deposition conditions will be used to fabricate an extended gate PCB-ISFET and we will characterise the performance aiming for a sensitivity of > 70mV /pH in the pH range 4-10. We will demonstrate the complete system for real-time monitoring and quantification of E. coli. Measurements will be performed in a fluid cell consisting of a 3D printed holder and PDMS gaskets using E. coli spiked into pure and environmental water with a known background of other bacteria. We will assess quantification of E coli via time-dependent, ISFET measurements of pH change and quantify the limit of detection for the qDAMP prototype. Alignment to EPSRC strategy: Aligned with the principles of ODA, the primary goal of this project is the promotion of the economic development and welfare in developing countries and is thus aligned with the EPSRC's role in the GCRF. We also anticipate benefits to the UK. In particular, this proposal will develop a novel, low-cost analytical technology that aligns with the aims of the EPSRC Physical Science theme, Analytical science and extends the position of the UK in analytical science and technology. Our low-cost diagnostic technology will also contribute directly to the EPSRC Healthcare Technologies strategy and has potential beyond healthcare, for example as an analytical tool for food security, environmental monitoring and bioterrorism.
Partners: INOV, University of Konstanz, CNR, FHG, VICOM, NASK, Technikon (Austria), IST, LEONARDO, TECNALIA...
In the domain of Cybersecurity Research and innovation, European scientists hold pioneering positions in fields such as cryptography, formal methods, or secure components. Yet this excellence on focused domains does not translate into larger-scale, system-level advantages. Too often, scattered and small teams fall short of critical mass capabilities, despite demonstrating world-class talent and results. Europe’s strength is in its diversity, but that strength is only materialised if we cooperate, combine, and develop common lines of research. Given today’s societal challenges, this has become more than an advantage – an urgent necessity. Various approaches are being developed to enhance collaboration at many levels. Europe’s framework programs have sprung projects in cybersecurity over the past thirty years, encouraging international cooperation and funding support actions. More recently, the Cybersecurity PPP has brought together public institutions and industrial actors around common roadmaps and projects. While encouraging, these efforts have highlighted the need to break the mould, to step up investments and intensify coordination. The SPARTA proposal brings together a unique set of actors at the intersection of scientific excellence, technological innovation, and societal sciences in cybersecurity. Strongly guided by concrete and risky challenges, it will setup unique collaboration means, leading the way in building transformative capabilities and forming world-leading expertise centres. Through innovative governance, ambitious demonstration cases, and active community engagement, SPARTA aims at re-thinking the way cybersecurity research is performed in Europe across domains and expertise, from foundations to applications, in academia and industry.
The biological pump refers to the mechanism by which carbon is assimilated by photosynthetic algae in the ocean photic zone and subsequently exported to depth upon death of the organisms. The largest part of this export production is generally remineralized as it travels throughout the water column where it depletes dissolved oxygen concentrations. A fraction of the export production may still reach the sea floor, where it is susceptible to be buried, thus inducing a net removal of CO2 from the ocean-atmosphere system. Therefore, the good appraisal of the response of the biological pump to changing environmental conditions is crucial to reasonably predict climate and ocean oxygenation impacts, both associated with past events and as will result from ongoing anthropogenic emissions. However, the behavior of the ecological system in the face of climatic changes and how it impacts the strength and efficiency of the biological pump remains difficult to predict. To address this, here I propose to investigate the sensitivity of the biological pump in a novel way – using a state-of-the-art ecological model including a representation of marine biogeochemical cycles. I will focus on past periods, which provide a whole evolutionary chronicle to which model outputs can be directly compared. Confrontation of model results with geological records will also allow me to develop a mechanistic understanding of the behavior of the ecological system in response to a wide range of environmental perturbations. The proposed approach constitutes an unrivaled opportunity to increase our understanding of the geological record and what it can tell us of relevance to the future. Lessons learned here, both positive and negative, have the potential to help inform the next generation of marine ecosystem models needed to make improved projections of future global change impacts on ocean ecosystems, and hence engaging a broad range of global change scientists and ultimately, policy makers.
Knowledge-based improvements of Li-ion battery cost, performance, recyclabiKnowledge-based improvements of Li-ion battery cost, performance, recyclability and safety are needed to enable electric vehicles to rapidly gain market share and reduce CO2 emissions. SPIDER’s advanced, low-cost (75 €/kWh by 2030) battery technology is predicted to bring energy density to ~ 450 Wh/kg by 2030 and power density to 800 W/kg. It operates at a lower, and thus safer, voltage, which enables the use of novel, highly conductive and intrinsically safe liquid electrolytes. Safety concerns will be further eliminated (or strongly reduced), as thermal energy dissipation will be reduced to 4 kW/kg, and thermal runaway temperature increased to over 200°C. Moreover, SPIDER overcomes one of the main Li-ion ageing mechanisms for silicon based anodes: notably, the loss of cyclable lithium, which should increase lifetime to 2000 cycles by 2022 for first life applications with further usefulness up to 5000 cycles in second life (stationary energy storage). In addition, SPIDER’s classic cell manufacturing process with liquid electrolyte will be readily transferable to industry, unlike solid electrolyte designs, which still require the development of complex manufacturing processes. Finally, SPIDER batteries will be designed to be 60% recyclable by weight, and a dedicated recycling process will be developed and evaluated during SPIDER. In addition, SPIDER materials significantly reduce the use of critical raw materials. Finally, four SPIDER partners are identified by the European Battery Alliance as central and strategic for the creation of the needed European battery value chain: SGL, NANO, VMI & SOLVAY. In conclusion, SPIDER proposes a real breakthrough in battery chemistry that can be readily adopted within a sustainable, circular economy by a competitive, European battery value chain to avoid foreign market dependence and to capture the emerging 250 billion € battery market in Europe.
Partners: KTH, ECO ESO ELECTRICITY SYSTEM OPERATOR, DIL DIEL, MIG 23 LTD, SIMAVI, SIVECO (Romania), IRETI SPA, L7 DEFENSE LUXEMBOURG SARL, COGEN ZAGORE LTD, City, University of London...
The EnergyShield project will develop an integrated toolkit covering the complete EPES value chain (generator, TSO, DSO, consumer). The toolkit combines novel security tools from leading European technology vendors and will be validated in large-scale demonstrations by end-users. The EnergyShield toolkit will combine the latest technologies for vulnerability assessment (automated threat modelling and security behaviour analysis), monitoring & protection (anomaly detection and DDoS mitigation) and learning & sharing (security information and event management). The integrative approach of the project is unique as insights produced by the various tools will be combined to provide a unique level of visibility to the users. For example, it will be possible to combine vulnerability scanning with automated threat modelling to provide insights into software vulnerabilities present in an architecture in combination with insights into what are the key assets, risks and weak links of the architecture. The toolbox will allow end-users to predict future attacks (as it provides insights to what attacks can be applied to the weakest links of the architecture) and learn from past attacks (for example using the insights from the vulnerability assessment and threat modelling to prevent attacks, and learning from attacks to update the probabilistic meta-model of the threat modelling). The toolkit will be implemented with the complete EPES value chain who will contribute to the specification, prototyping and demonstration phases of the project. Although the toolkit will be tailored to the needs of EPES operators, many of the technology building blocks and best practices will be transferable to other types of critical infrastructures. The consortium consists of 2 large industrial partners (SIVECO and PSI), whereof SIVECO is taking the lead supported by 6 innovative SMEs, 3 academic research organizations and 7 end-users representing various parts of the EPES value chain.