The micronutrient selenium (Se) is critically important for optimal health. The Se status of the UK population is only marginal and may increase risk not only of viral infections but also of a number of major diseases including prostate and colon cancer. However, the mechanisms by which Se intake affects gut health are poorly understood and the impact of interactions between Se intake and genetic factors not defined. In this project we will adopt a systems approach to describe the effects of Se on the intestinal epithelium and the impact of a specific genetic variant. The project will also provide a proof of principle of for such analysis of nutrient-gene interactions. The programme of work will combine mathematical modelling with in vitro molecular techniques, experiments in cell lines and work with transgenic mice to assess the functional effects of a key variant in the gene that codes for the selenoprotein glutathione peroxidase in response to Se intake. Measurements will be made of selenoproteins and related biochemical pathways and the experimental data will be used to refine a mathematical model of selenoprotein metabolism and its downstream effects. The systems model generated in this programme will allow prediction of the how Se supply modulates biochemical pathways and cell function. Validation of the model in a physiological context will lay the basis for future testing of the model in human studies. The major outcomes from this programme will identification of novel functional biomarkers of Se status for use in later human studies and an increased ability to model nutrient metabolism at different physiological levels in relation to genetic factors.

Terminology Explained PUF stands for Physical Unclonable Function and can be used to uniquely identify a given device/component. PUF's are based on the premise that no two components (i.e. a RAM module) are the same due to the microscopic physical variations that occur during manufacturing and are near-impossible to replicate accurately and cost-effectively. These physical variations can be used to aid in security. One application of PUF's which is being pursued by this project is the use of PUF's for encryption over the standard key-based encryption which is often poorly implemented (with regard to key-management and storage) and un-optimised for IoT devices (in regard to power consumption and processing power). Key Objectives The research project as a whole can be broken down into 3 stages (projects) with each stage acting as a project in itself. It is only expected for the first two projects to be fully completed. Project 1 - Fingerprinting Sensors On a given device (or type of device), this project aims to fingerprint the device as a whole using the output of multiple sensors. Technical Abilities Required: *Machine Learning - Commonly used technique for fingerprinting *Extracting Raw values from sensors *Sensor background theory (e.g. Calibration) *Maths [Vectors, proofs] *Create an algorithm for fingerprint generation from multipole sensors (*Novelty Aspect) Key Reference Paper: SensorID: Sensor Calibration Fingerprinting for Smartphones Expected Duration: 1.5 Years Project 2 - Sensor PUF Creation and Proof [Main Focus] This project follows directly from the first by using the extracted values from the previous project to create a sensor-based PUF. By the end of the project, a limited proof-of-concept of this implementation is expected, at a minimum. Technical Abilities Required: *Maths [Proofs, Vectors] *Sensor PUF Creation, Implementation and Proof (*Novelty Aspect) Key paper of reference: Texture to the Rescue: Practical Paper Fingerprinting Based on Texture Patterns Expected Duration: 1.5 Years Project 3 - Sensor PUF Application In the unlikely scenario that time permits, this third project consists of applying the findings from the previous projects; applying the sensor PUF to an existing IoT product/environment. Following this, an authentication-based attack will be enacted on the IoT environment in question prior to and following the implementation of the sensor PUF to show the effectiveness of the PUF. Technical Abilities Required: *Conducting an Authentication-Based Attack *Emulating an IoT Environment *Applying Project 2 (Implementing a PUF) to Existing Set-Up Expected Duration: ~1 Year Project Novelty The overarching novelty of the project is the generation of PUF's from sensors to be used in authentication in an IoT environment. PUF's are commonly implemented using RAM, Processors, FPGA's and ASIC's, but there are currently no papers on sensor PUF's (only a patent). What question does project intend to answer The question the project intends to answer is: Are sensors (literally) the key to a secure IoT environment? Can PUF's generated from sensors reliably be used to increase the security of an IoT environment without the drawbacks of standard key-based encryption?

Aging of cells and organisms is largely determined by damage to cellular molecules, the efficiency of damage repair and the cellular mechanisms of response and adaptation to the remaining damage. We are primarily interested in the mechanisms and the importance of cellular senescence, which is the permanent loss of the ability of cells to divide and growth. Damage to DNA, either in the form of loss of telomeres (the very ends of all chromosomes), or of DNA breaks, is a major trigger of cellular senescence. Thus, senescence prevents the growth of cells with damaged, mutated DNA, which means that it protects organisms against tumour growth. However, senescent cells are not only proliferation-inhibited, they also show very different gene expression pattern and functionalities from their young, proliferating counterparts. In other words, the presence of even few senescent cells impacts on the surrounding tissue and these cells can change function of the organ they reside in, thus contributing to ageing. While the signals connecting DNA damage or telomere loss with proliferation arrest have been reasonably well characterized in recent years (and we have contributed to this), the whole network of signalling processes generating the complete senescent phenotype is still very much unclear, despite its obvious importance for the ageing process as a whole. We are convinced that a thorough characterisation of this network of signalling and response processes will not only provide ample clues to understand why old cells and organs are more frail and vulnerable to disease. It might also indicate possible targets for intervention, at the molecular level, in the cellular ageing process and thus contribute to postponing age-related disease. To study DNA damage responses and repair, we need technologies to measure accurately the timing of changes in a great number of factors possibly involved in the response, and of the interactions between them. This generates a vast number of data, and we need mathematical and statistical methods to integrate and evaluate these data and to draw conclusions from them. All such technologies have been established on-site over a number of years and are now ready to use. However, we also need a means to inflict DNA damage in a well-controlled fashion and at a defined point in time. Ionizing radiation is a well-accepted generator of DNA damage, and an X-ray irradiator is both most versatile (the characteristics of the radiation can easily be modified using different filters) and least hazardous (no permanently radioactive material involved). So far, the necessary equipment is only available off-site. This seriously compromises our ability to perform exact time-course analyses, as our results may become dependent on traffic conditions in town. Moreover, valuable research time is wasted on travel and logistics is complex. It is envisaged that a growing number of research groups on the Campus will become engaged in similar research projects within the next few years. An X-ray irradiator will thus remain an essential part of the research infrastructure on the Campus for the years to come.

PROteolysis Targeting Chimeras (PROTACs) are a promising and recent technological development utilised in the degradation of proteins in eukaryotes. Application in bacterial pathogens however has been overlooked as protein degradation in this way was thought to be unique to eukaryotes. Recently it has become clear an exception to this exists, Mycobacterium tuberculosis and other actinobacteria, have been shown to possess a highly analogous degradation system. Consequently, this project will expand our current interest in Mycobacterium tuberculosis (Mtb) pathogen and focus on the development of MycoTACs, the first PROTAC like molecules for use in Mycobacterium tuberculosis.