Kaposi's sarcoma-associated herpesvirus (KSHV) is a virus that is linked to the development of a type of cancer known as Kaposi's sarcoma (KS) in individuals with compromised immune systems. KS is one of the top 10 cancers identified in men, women and children in South Africa, where it is the third most common cancer in African men. Despite this, there are no specific or effective treatments for KS that target the KSHV virus directly. As KS is an AIDS-defining disease, controlling HIV/AIDS and improving immune function using antiretroviral agents has been investigated as a possible treatment for KS. However, this is not always effective as many patients with well-controlled HIV infection still develop KS, and some individuals can experience life-threatening side-effects once they start antiretroviral therapy. Consequently, focused, specific and effective anti-KSHV therapies are urgently needed. KSHV is a member of the herpesvirus family and has two distinct life cycles in cells, a persistent life-long infection where the virus is mainly dormant (known as latency) and an infectious cycle that produces new viruses from the host cells (known as lytic replication). Uniquely for KSHV, both the latent and lytic replication cycles contribute to the development of KSHV-associated cancers. Therefore, it is essential to study the virus-host cell interactions which regulate both latent and lytic phases to fully understand KSHV-related disease. Moreover, inhibiting either or both phases may provide an opportunity to develop novel antiviral strategies to inhibit KS formation. This project focuses on a family of proteins found in host cells known as molecular chaperones. Molecular chaperones are needed for KSHV to undergo both latent and lytic replication cycles, acting as broad host cell factors for viral function. Molecular chaperones are themselves regulated by a family of host proteins known as co-chaperones, which are accessory proteins that fine-tune the function of chaperone systems. We have exciting preliminary data implicating the host co-chaperone STIP1 in multiple aspects of KSHV biology. This proposal will investigate how STIP1 functions during the KSHV latent and lytic phases and develop new ways to inhibit STIP1's function for use as KSHV-targeted therapeutics. We will apply a combination of molecular virology and drug discovery to describe in detail the viral and human cell processes controlled by STIP1 during KSHV latency and lytic replication. We will then use that information to design molecules capable of inhibiting STIP1 function in KSHV, which could subsequently be developed into KSHV-specific antivirals in future.

The Square Kilometre Array (SKA) is a new radio interferometric telescope currently under design, with broad-ranging science goals from uncovering the mysteries of dark energy and dark matter, to the study of extra-terrestrial life. Designing and building the SKA is an ambitious international endeavour, with a budget of 1.5 billion Euros. Through our research we will develop the novel algorithms required to recover images from the raw data recorded by the SKA -- a tremendous computational task -- making the ambitious science goals of the SKA achievable. A new era of radio astronomy is approaching rapidly. The design of the SKA is well underway, with construction scheduled to begin in South Africa and Australia in 2018. Moreover, many pathfinder telescopes intended to develop and test the core technology of the SKA are starting to come online now. The SKA will be comprised of thousands of separate telescopes, all acting together through a technique called aperture synthesis. The resulting telescope array will synthesise one single massive telescope, with an effective size of one square kilometre, equivalent to approximately 200 football pitches. Radio interferometric telescopes like the SKA were invented in the UK by Ryle and Hewish, who won the Nobel Prize in 1974 for their achievements. These first radio telescopes consisted of just a handful of individual dishes. The thousands of individual telescopes making up the SKA will produce a tremendous big-data challenge, even taking into account the advances in computing expected over the coming years -- the anticipated data-rate of the SKA is expected to be many times greater than current world-wide internet traffic. Furthermore, the SKA will see a very wide field-of-view, which complicates the modelling of the telescope significantly and dramatically increases the computational requirements further still. We will develop novel algorithms to overcome the tremendous big-data and wide-field imaging challenges of the SKA. To do so, we will exploit the revolutionary new theory of compressive sensing. Compressive sensing is a ground-breaking new development that has wide-ranging implications for data acquisition in many fields. In radio interferometry, it suggests that high-fidelity images may be recovered from many fewer raw data telescope measurements than previously thought possible, or alternatively, that much higher image reconstruction fidelity can be achieved for a given set of raw data measurements. We will develop novel compressed sensing techniques for radio interferometric imaging, incorporating computationally efficient algorithms to model the wide-field setting. Rather than making incremental improvements to traditional imaging algorithms, we will take a transformative approach, developing radically new algorithms for imaging the raw data observed by radio interferometric telescopes. We will apply our techniques to observations made by the recently built South African KAT-7 telescope, one of the SKA pathfinder telescopes. This will pave the way towards the integration of our techniques into the imaging pipelines of current and future radio telescopes. By overcoming big-data and wide-field imaging challenges we will ensure that the SKA reaches its full potential, making possible its ambitious science goals and, if history is an accurate guide, many serendipitous scientific advances that we cannot yet predict or comprehended.

The oceans are not warming evenly and those areas that are warming fastest are becoming the world's natural laboratories for research to increase scientific understanding, knowledge and tools to allow us to adapt wisely, efficiently and effectively in order to meet the challenges of a warming environment. Such 'hotspots' occur in all regions of the globe, from polar to tropical, and affect developed and developing countries. However, poor coastal communities in low-income countries are those where the impact will be felt most acutely, and where impacts of climate change are most likely to exacerbate existing inequalities and social tension. There are no simple, conventional solutions to addressing adaptation to climate change in poor communities. Practical experience and scientific information from these areas is limited and there is an urgent need to improve and test the theories that underpins existing efforts. This project will develop an innovative rapid approach to integrate and apply global scientific and local information and knowledge. The approach will be applied in Madagascar, one of the poorest countries affected by a marine hotspot and will work as a case study for applying to other global hotspots. At its core is an expert workshop, which will bring together a multi-disciplinary team of world-leading researchers with experience from climate change adaptation on the larger, global-scale, regional experts and specialists with detailed knowledge of the hotspot area, and community representatives who can provide a rich local understanding, knowledge and context. Together they will identify key areas of environmental change and their likely consequences for local populations. They will explore adaptive solutions, develop recommendations for future action to minimize societal impacts on low-income communities in the hotspot region, and most use experiences and information from this participatory process to develop and test current theories for developing climate change adaptation strategies. The scientific insights generated by the research will be included in a synthesis paper, and in dissemination/awareness materials targeting the local audience. While this project will not be able to test current theories by implementation, it will provide a valuable opportunity for intensive discussion and exchange on adaptive solutions between experts in the theory and coastal stakeholders who are intimately familiar with their own circumstances and needs. The outcomes from the project will therefore enrich current understanding of adaptation and adaptive capacity and generate proposals for revising it where necessary.

Biodiversity change directly threatens the livelihoods, food security, and cultural and ecological in-tegrity of rural subsistence-oriented households across the developing world. People will be forced to respond to it in ways that either mitigate loss of biodiversity and ecosystem services or that ex-acerbate losses. An unprecedented extinction of species is underway, and climate change is af-fecting species' range and phenology, leading to new species configurations that affect ecosystem services in unpredictable ways. With climate change and continued habitat alteration entailed in human population growth, 'novel' ecosystems will become even more prevalent. In the UN Interna-tional Year of Biodiversity, scientists and policy makers must recognise that humans, biodiversity, and ecosystems must co-evolve and co-adapt. However, Human Adaptation to Biodiversity Change is not considered as theme in any international, regional, or national science or policy for-ums. There is a dearth of scientific research about HABC, so scientists and policy makers lack mandates, conceptual frameworks, knowledge, and tools to project or predict human responses and their actual or potential outcomes, synergies, and feedbacks. Indeed, 'A significant new re-search effort is required to encourage decision makers to consider biodiversity, climate change and human livelihoods together' (Royal Society 2007). At the same time, there is a call for a 'para-digm shift' in adaptation thinking away from top-down planning and toward supporting local adapta-tion. Local adaptation efforts go unnoticed, uncoordinated, and unaided by outsiders and, unless policy makers become aware of the importance and extent of autonomous adaptation processes and understand what influences their outcomes, adaptation and mitigation policies may be ineffec-tive or counter-productive. This project's aim is to kickstart the development of appropriate conceptual frameworks, methods and integrated models for understanding human adaptation to change in biodiversity and related ecosystem services that can eventually be used to predict outcomes for biodiversity, eco-system services and human well-being in highly biodiversity dependent societies, and provide evi-dence for the utility of these outputs to a new network of researchers and policy makers. The build-ing blocks for development of concepts, methods, tools and models are a) local information or knowledge systems and monitoring capacity, b) local valuation of biodiversity and related ecosys-tem services; c) integrating biological resources and ecosystem services into an understanding of livelihood processes, d) assessing perceptions, risks, needs, and ability to respond, and e) under-standing biological and welfare outcomes and feedbacks. The project joins partners from anthro-pology, economics and ecology/biology at Oxford, Kent and SOAS, with partners from South Africa and India. Partners will jointly elaborate the conceptual framework in a first intensive workshop us-ing a scenario building protocol. Then, teams incrementally develop and evaluate research proto-cols and methods and collect primary data in a field research site in the Western Ghats, and re-sults are initially modeled. A second workshop revises the scenarios and prepares a second field data collection phase. This iteration permits further grounding of the conceptual framework and methods, and development and testing of a stronger, less aggregative model based on much bet-ter decisions about how different variables interact. After the second field research phase, scenar-ios are revised and integrated analysis and modelling of the data is done, and variables, variable sets, or system state indicators that are useful for monitoring biodiversity, ecosystem services and human well-being with biodiversity/ecosystem change are identified. A science-policy network is kickstarted (see impact plan).

South Africa is committed to aligning itself with the 2030 Agenda for Sustainable Development Goals (SDGs) and the Paris Climate Change Agreement. The Council on Higher Education (CHE) has pointed that South African aspirations for SDGs are vested in the work and roles of academic staff. The CHE (2014) also pointed that the subject content knowledge and pedagogical knowledge of most South African university staff is poor and that this is a major cause of inadequate learner achievement and mismatch with employability needs. There is no systematic attempt to infuse SDGs in HEIs so far and most of teaching methodology applied in the partner institutions, as well as in South Africa in general, focuses on lecturing and limited use of: i) problem-based learning strategies; ii) placed-based pedagogy; ii) utilization of ICTs as enabling pedagogical tools, and other innovative teaching/learning tools suitable to address SDGs challenges. This mismatch should be bridged through the professionalisation of undergraduate academic teaching to address SDGs in multiple disciplines. HEIs in South Africa should introduce and promote cross/interdisciplinary approaches to teaching, learning and assessment, helping students develop their breadth of understanding and building knowledge and practice on SDGs. The proposed project addresses the modernization of curricula in multiple academic disciplines to infuse SDGs through capacity building of academic staff in innovative teaching and learning tools, methodologies, ICT-enabling pedagogical approaches in nationally prioritized subjects, such as biology, agricultural, environment, engineering, health. By the end of the project, there will be a significant cohort of academic teaching champions, who will drive wider changes in their HEIs and society by implementing SDGs in line with the South Africa’s National Development Plan and in alignment with the 2030 Agenda for SDGs.