Preventable and treatable diseases cause a huge amount of illness and a huge number of deaths in Africa. Infectious diseases, like malaria, are some of the biggest killers. Not only do these diseases cause major health problems for those infected, they are also a major financial burden to individuals and communities, and they hinder economic and societal development for whole countries. The poorest and most marginalized communities are usually the worst affected, and so these diseases exacerbate inequalities associated with geography, gender and ethnicity. Current strategies to tackle infectious diseases in the poorest settings rely on rudimentary approaches to diagnosis and treatment, such as reliance on a few clinical features (like fever, difficulty breathing or pallor) and very few simple tests to decide the treatment someone should receive. This approach is necessary because there are rarely diagnostic laboratories nearby to provide comprehensive testing, and even if there are, their services are often too expensive. Unfortunately, the simple methods of diagnosis often result in incorrect diagnosis, and provide little data from which to learn how to improve. A wrong diagnosis can mean the wrong treatment is given, resulting in prolonged illness or death, whilst at the same time encouraging overuse of some treatments like antibiotics or anti-malaria drugs, which can drive resistance to these drugs. A revolutionary solution to this problem is to develop a new generation of digital diagnostic tests which can be used at the point-of-care in even the hardest-to-reach communities. These diagnostic tests are not only more accurate and faster than current alternatives but potentially cost saving. Digital diagnostics have the potential to transform the situation by linking the precision typical of an advanced laboratory with the portability, connectivity, analysis and support that can be provided through a modern smart phone. This means tests can be administered anywhere and anytime by a wide range of healthcare workers with minimal training. For example, a drop of blood collected from the tip of the finger of child by a health worker in their community, could be applied to a tiny microchip powered by a mobile phone battery, and within 15-20 minutes a result could be available to make a diagnosis. The results are transmitted from the microchip to a smartphone via Bluetooth so no internet connection is required. If "Malaria" is detected, the device can notify the healthcare worker of the type of malaria and the correct treatment. The smartphone could also send the result and location data via the mobile network to a remote computer system, which could determine whether there is an unusually high level of malaria in that area and, if so, notify the national Malaria control program that extra resources are required to tackle an outbreak before it gets worse. Thus the child benefits from the right treatment, the community benefits from the intervention, and the health authorities benefit from being able to allocate the resources available to where they are most needed or will work best. The real-time data also allows international organizations to make more effective policies to tackle malaria and allocate funding. In our proposal we are developing a network of scientists with diverse skills and expertise, joining them together with commercial companies that manufacture diagnostics, and organizations who work directly in African countries putting new disease control tools and strategies into practice. This network will plan how best to develop new digital diagnostic devices to tackle health problems in Africa. The network will test its strategies by specifically planning the development of a new digital diagnostic test device for malaria and drawing out a roadmap to its implementation.

An integrated compositional and structural approach to understand keratin hair fibre damage using mass spectrometry based proteomics and surface analysis techniques

Mammalian development requires multiple, rapid cell divisions in order to support the growth and morphogenesis of the developing embryo. Given the limited number of early embryonic cells within the embryo that give rise to all cells in the adult body, errors occurring during cell division (mitotic errors) in these cells could have devastating consequences, from congenital defects to embryonic lethality. Yet, despite the pivotal importance of preserving genome integrity during early embryogenesis, embryonic cells are particularly prone to mitotic errors. Thus, fundamental unanswered questions in developmental biology are what makes embryonic cells susceptible to mitotic errors and how is robust development achieved against the backdrop of high rates of mitotic errors. Although early human embryogenesis is experimentally inaccessible, embryonic stem cell (ESC) lines can be derived from the inner cell mass of an early blastocyst. Therefore, ESCs represent a unique and powerful tool for studying otherwise intractable stages of development. We have recently demonstrated that the high frequency of mitotic errors characteristic of early embryos is also evident upon in vitro culture of ESCs (Zhang et al., 2019 Stem Cell Reports 12:557; Halliwell et al., 2020 Stem Cell Reports 14:1009), indicating that the susceptibility to mitotic errors is an intrinsic property of early embryonic cells and that ESC will provide a good platform for determining the A 2021-entry-WR-DTP-CASE-Form-A-Barbaric, Fellows Page 3 of 13 mechanistic basis of these errors. The overall goal of this project is to elucidate molecular mechanisms governing a high incidence of mitotic errors in ESCs and to assess the impact of chromosome gains or losses (collectively known as aneuploidy) on the developmental potential of ESCs.

Commercial organisations now have unprecedented amounts of data on consumer behaviour, market dynamics, buying patterns, and consumer characteristics. The challenge is how to draw meaningful information and insights from this data to inform strategic decisions about product development and marketing. This project offers an outstanding opportunity to work with Linney, a world-class, multi-channel marketing services group, to research the potential and limitations of data analytics in an applied marketing context. Drawing on the literature, marketing theory and cutting-edge data analytical methods you will work with Linney and some of their leading clients, many of which are household names, to explore the strategic role of data analytics in commercial marketing.

Our research with the particle physics rolling grant at Sheffield attempts to progress understanding of some of the most important questions concerning the origins and make-up of the Universe. One of these big questions is to understand what gives fundamental particles their mass. Part of our work on the huge ATLAS experiment at the Large Hadron Collider (LHC) at CERN in Geneva is aimed at this question, in particular to see if the famous Higgs Boson particle exists. The best theories we have to explain particle mass predict that it should be there. We will play a key role in analysing the vast amount of data soon expected to make this exciting discovery. Another search at ATLAS will be to determine if the so-called supersymmetry (SUSY) theory is correct. This is our best prospect for understanding how particles interact at high energy and itself predicts a new class of particles. The concept states that for every known fundamental particle there exists a super-partner particle. We worked for many years developing the key silicon technology now installed in ATLAS to search for these particles. Now we are ready with our software to play a key role in analysing the data that will hopefully discover that they exist. One of the implications of SUSY theory is the likelihood that the most stable new particle, the so-called lightest supersymmetric particle (LSP), probably is very abundant throughout the Universe, making up about 25% of its mass. This would easily explain one of the big mysteries in physics, the so-called Dark Matter seen by astronomers from its gravitational effects on stars and galaxies. Our group has pioneered techniques to search directly for dark matter particles in the laboratory and is participating in a new multi-national venture, EURECA. This will build a tonne-sized device using low temperature superconductors to perform a new search. We will contribute to the key aspect of how to shield the experiment from natural background particles, like muons. Another mystery in the Universe are the strange properties of its most abundant particle, the neutrino. This has only recently been found to have a small mass and to readily change form between three different 'flavours' while propagating through space. Details of this are not fully understood but it is known that if properly unravelled it might answer another big question, why there is so little anti-matter in the Universe. We are working on these questions through participation in the big international T2K neutrino beam experiments in Japan. We are building a key component of the detectors and will, within two years, start to analyse the data to unravel these issues. T2K probably will not do a full job, so we have instigated in the UK work on a new neutrino detector concept, based on liquid argon, contributing to the FJNE programme. We plan to build test devices to enable the next generation of neutrino experiments to follow T2K. This is linked also to our work on accelerator technology, MICE, where we are building test beam targets. This is a vital step towards the ultimate facility, a neutrino factory. We are working on key technology for this within the UKNF project. Finally, much of the hardware and computer code developed for these fundamental studies have great relevance well outside our main research. There are many examples, involving projects with a dozen UK companies. For instance, our work with Corus Ltd. on new techniques for neutron detection, has allowed development of new monitors to detect illicit transport of nuclear materials at ports. This will continue now and broaden into medical applications. Our dark matter work has produced a new national facility for underground science, the Boulby laboratory. Here we have started a new project on climate change, SKY, to explore the effect of comic rays on cloud formation.