Discovery and development of new drugs for human use remains a slow, expensive and inefficient process. A critical point of failure in drug discovery programmes is the preclinical evaluation of drug candidates with only about 30% success rate. Consequently, new methodologies to increase success rate at the preclinical drug development stage are needed. This project aims to develop a new, environmentally sustainable, prototype device to allow for high-throughput in vitro characterisation of drugs pharmacokinetics (PK) coupled with in silico kinetic models to better predict drug performance in vivo. The gold-standard approach to investigate drugs PK involves using Positron Emission Tomography (PET) and microdosing techniques. However, these techniques can be expensive and often require a large number of animals. Importantly, although the use of animals can be useful to assess drug distribution, metabolism and therapeutic effects, species differences versus humans often decrease the translational success rate of a new drug. Therefore, there is a need to design more efficient drug discovery pipelines and to increase confidence on selection of the lead compounds at early stages of the process. To this regard, the recent development of the so called "body-on-chip" in vitro technology holds tremendous promise as a platform to predict drug responses in vivo. Recently, our team has developed a new "body-on-chip" prototype device, which has a number of important properties that position it uniquely in the "body-on-chip" arena, namely: Perfusion through the capillary system and organ compartments capable of mimicking the human circulatory system; Easy to use and versatile organ compartment inserts capable of housing a large number of cells, required for accurate quantification of concentration of drugs in cells by high throughput and mainstream chromatographic methods; Environmentally sustainable re-usable design, requiring only a simple clean protocol between experiments; Reduced cost of manufacturing as well as reduced maintenance costs, as the "body-on-chip" can be re-used and the associated peristaltic pump required to maintain flow through the device is commercially available off the shelf. Our new "body-on-chip" device has the potential to enable predictive PK studies in vitro as well as individual tissue drug exposure analysis and drug-target binding kinetics quantification, which currently cannot be accomplished with available "body-on-chip" devices.

Work at Warwick has demonstrated that river sediment bed-form, such as particle courseness and ripple height, has a major influence on the behaviour of tracers, but the implications for the fate of chemical pollutants remain to be elucidated. Furthermore, in many developing countries, untreated waste water is routinely discharged directly into surface water, and is associated with high levels of suspended solids and biochemical oxygen demand. However the implications of direct discharge conditions for the biodegradation of chemical pollutants is not known. The student will work with microbiologists, civil engineers and environmental modellers to elucidate the effect of bed-form characteristics on the diversity and pollutant degrading potential of microbial communities inhabiting biofilms at the sediment surface, and the way in which direct discharge scenarios affect interactions between bed-form, microbial community composition and pollutant biodegradation rates. The following hypotheses will be tested: 1. Chemical pollutant distribution patterns within river sediment are determined by bed-form 2. Bed-form controls microbial community structure and diversity 3. Bed-form affects the development of catabolic communities and biodegradation rates 4. Direct discharge conditions affect establishment of river-bed microbial communities and biodegradation processes Following the experimental phase of the work the student will spend six months at Unilever to develop approaches to incorporate the results into general exposure modelling frameworks for developed and developing countries. The studentship provides inter-disciplinary training in microbiology, molecular biology, environmental hydraulics and modelling. The industrial partner will provide funding to enable establishment of micro-flume experimental systems and the use of cutting edge techniques, including high throughput sequencing to assess microbial diversity. Furthermore funds will be made available for the student to attend regular national and international conferences and to spend 6 months at Unilever for training in exposure modelling and environmental risk assessment.

Infectious diseases represent a continuous and increasing threat to human health both nationally and internationally. In the UK, rapid increases in antimicrobial drug resistance (AMR) and recent experiences from the SARS-CoV-2 pandemic, highlight the need for investment in solutions to manage and eliminate these threats to human health. There is scope for optimism however as running parallel to these challenges, technological advancement and innovation are creating new opportunities for managing and mitigating against infectious disease crises. These include improved platforms for diagnostic, vaccine and therapeutics discovery, as well as advancements in disruptive technologies such as artificial intelligence (AI), the Internet of Things (IoT), Big Data, robotics and drone technology. It is clear from the current COVID-19 pandemic that academic partnerships with industry are key to quickly developing the required tools and the elimination of bottlenecks essential to addressing the health needs. Whilst it is broadly recognised that strengths in basic science reside in academia, it is the industrial sector that has the expertise and capability to bring innovations to market quickly. The largest cluster of infection-focused businesses in Europe is growing in the North West. In addition, the Liverpool City Region (LCR) has been identified in a 2017 BEIS-commissioned "LCR+" Science & Innovation Audit (SIA), to possess a concentration of "smart specialisation" opportunities in interrelated sectors of 4IR/advanced manufacturing, clean growth, digital and createch, and health and life sciences. Demonstrable and genuinely distinctive science and industry assets and capabilities include the Materials Innovation Factory, the STFC Hartree Centre supercomputer and the IBM Watson platform. The key challenge that forms the basis of this application is how to unlock the innovation potential of this unique scientific and industrial cluster to develop solutions that address the described health needs of existing and emerging infectious diseases. Aims &Objectives: Setting up links between academia and industry requires mutual trust, commitment, motivation and the creation of bilateral value through a common purpose. This can be challenging to set up as the two sectors generally have different goals and objectives and operate with different procedures and cultures. The overarching aim of this application is for the secondee to gain the relevant knowledge, experience and skills that will aid him in the development of a strategic road map and effective operational models that support the development of innovative solutions to current and emerging infectious disease-related health needs. Towards this aim, the specific objectives include: (i) To gain broader knowledge of the regional private sector scientific and industrial strengths, especially in disruptive technologies. (ii) To gain deeper knowledge and experience of effective enabling activities and operational models used to foster a climate of innovation between academia and industry. (iii) To gain a better understanding of the sector skills priorities and knowledge of effective mechanisms that facilitate career mobility. (iv) To gain a greater understanding of the role that academia can play to increase the productivity of industry and the impact that these relationships and investments make both regionally and nationally. Successful completion of this secondment has the potential to benefit both the secondee and the secondment organisation by fostering a sustainable partnership that (i) accelerates the generation of breakthrough innovations for the benefit of human health, (ii) results in upskilling of the workforce enabling sector mobility and (iii) impacts by increasing the productivity of the local and national economy. These outputs are directly aligned to the aims of the UKRI Innovation Secondment scheme.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.