Student completing MRes in first year. Project details will be added when student begins doctoral studies in year 2.

Outer space is critical to our daily lives in countless invisible ways - but space is not protected by the same environmental rules that applies on Earth. Space lawyers tend to conclude that space is not part of 'the environment', based on a common interpretation of the four core space treaties, especially Article IX of the Outer Space Treaty. This legal conclusion rests upon certain historical presumptions that are rarely considered in their own right. By assessing environmental law in space by reference to history, this thesis will explicate these presumptions, reassessing the environmental status of space from the ground up.

Background: Autophagy is a key homeostatic process where damaged cellular components are sequestered into autophagosomes and degraded by the lysosomes. Impairment of autophagy has been implicated in inflammatory, neurodegenerative and age-related diseases including age related macular degeneration (AMD). Bi-allelic mutations in the DNA damage regulated autophagy modulator 2 (DRAM2) result in development of retinal dystrophy with early macular cone photoreceptor involvement. To better understand the role of autophagy in retinal cell function, we have generated induced pluripotent stem cells (iPSCs) from two patients with different mutations in the DRAM2 gene. Correction of these DRAM2 mutations using CRISPR/Cas9 in situ gene editing techniques yielded patient-specific isogenic iPSCs. Side by side comparison of DRAM2 mutated and isogenic control photoreceptors and RPE cells demonstrated a profound loss of DRAM2 protein and a significant downregulation of key lysosomal hydrolases (CTSD, NPC2, TPP1, PPT1) that are involved in the late stages of autophagy by breaking down proteins, lipids and associated sugars. In turn, lipid accumulation and loss of RPE and photoreceptor viability were revealed by transmission electron microscopy and lipidomic analyses. Together these data have led us to hypothesise that: 1) DRAM2 is critically involved in vesicular transport of key lysosomal enzymes from the trans-Golgi network to the lysosomes; 2) DRAM2 deficiency/dysfunction results in impaired transport of lysosomal enzymes which in turn causes lysosome dysfunction and lipid/waste accumulation in photoreceptors and RPE cells; 3) unprocessed waste accumulation causes progressive photoreceptor and RPE cell loss. Building upon these pilot data, we here propose to 1) assess DRAM2 processing and trafficking in photoreceptors and RPE cells; 2) dissect the DRAM2-associated functional module; and 3) test the effect of DRAM2 supplementation in abolishing lipid and waste accumulation in photoreceptors and RPE cells. Experimental approach: In vitro culture and differentiation of DRAM2 iPSCs and isogenic controls to photoreceptors and RPE cells using protocols established in our groups. Yeast two hybrid combined with site directed mutagenesis and directed co-immunoprecipitation assays will be used to identify and validate DRAM2-interacting proteins. Tagging of endogenous DRAM2 with a split-GFP system combined with confocal microscopy and differential centrifugation and density-gradient dependent organelle isolation will be used to address DRAM2 processing and trafficking through the endoplasmic reticulum and trans-Golgi network to late endosomes and lysosomes. Importantly AAV based supplementation of DRAM2 will be tested to restore expression of functional DRAM2 in photoreceptor and RPE cells to reverse waste accumulation and loss of viability.

TBC

Austerity, technology, vulnerability: the role of digital technologies for young people in situations of vulnerability and the organisations which support them The 2008 financial crisis became the justification for some of the deepest cuts to public services in the history of the United Kingdom (UK) (Lowndes and Pratchett, 2012), enabling the relatively unimpeded enactment of austerity policies since 2010. Whilst this is often claimed as a retreat of the state and a stripping back of its responsibilities, in practical terms, the state became more, yet 'selectively' active (Harvey, 2007) in favour of the interests of capital. The impacts of this were wide-reaching, and intensified the transformation of the politico-economic and sociocultural environment of the country in aid of the neoliberal project. Whilst no area of UK policy remained untouched by austerity policies, one of the key areas of financial cuts and policy transformations have been services delivered to children and young people, which have seen larger reductions in levels of funding than public services generally (Youdell and McGimpsey, 2015). Austerity has altered the dominant political condition into one of scarcity and precarity (Berlant, 2011), fundamentally altering the values, practices and experiences of young people and the organisations which work to support them. Increasingly, these organisations are charities and voluntary sector organisations, who have aimed to fill the gap in provision left by the state in the wake of austerity (Clayton, Donovan and Merchant, 2015). As charities become increasingly responsible for the provision of services to young people in situations of vulnerability, they find themselves operating in a heavily marketized and financialized environment, competing against each other for 'tenders' for contracts to deliver vital services (Buckingham, 2012) or for funding from grantmaking organisations. The neoliberal, marketized mindset which this results in means that charitable decisions cannot ever be made solely for a public good but instead must have an eye towards keeping the charity 'competitive' or to demonstrate the 'impact' of the organisation's work. In parallel to these developments, digital technologies have become more widely used. Whilst this affords young people in situations of vulnerability quicker, easier access to services, connections to people they care about, and things that they enjoy, the rise of platform and surveillance capitalism via these technologies has resulted in the creation and extraction of data for the purposes of generating wealth for private companies (Srnicek, 2016). In the specific case of young people in situations of vulnerability - who are more prone to having data created about them that they are not privy to - these technologies may be used to make decisions about them which fail to contextually understand 'the whole story'. In such a situation, digital technologies may actively reproduce inequalities rather than mitigate them. As organisations who work with these young people become increasingly encouraged to engage with the digital, this PhD aims to understand what happens when these two worlds meet. Firstly, what are these organisations like, post-austerity? What are their practices and processes? How do they (and their young people) imagine their worlds? Secondly, how are the cultures of the digital beginning to affect these organisations? How do organisations see and engage with the digital, and how do designers and developers imagine both their own work and the work of these organisations? Finally, in light of these points, how can we design and use technologies with young people in situations of vulnerability that respect their agency and which meaningfully contribute towards their lives?