“Give Me Your Hand and I’ll Teach You How To Build”: Travelling Practices of Participation in Housing, from Albania to the UK

In this thesis two stories of participation in housing entwine across space and time. The first involves a migrant community living in an informal, self-constructed neighbourhood called Bathore on the outskirts of Tiranë, Albania, who benefitted from a participatory upgrading programme with a local planning NGO, from 1995-2005. The second involves a group of individuals in housing need who built a prototype house in collaboration with the researcher, entitled ‘Protohome’, which was temporarily sited and open to the public in Newcastle upon Tyne, UK, in 2016. The aim of this research is to locate and test alternative approaches to housing informed by, and embedded in, the conditions of the contemporary UK context: austerity, welfare cuts and caps, rising homelessness, housing precarity and the residualisation of social housing. The research is not simply a design exercise, but seeks approaches to housing which are collaborative, participatory and socially sustainable and which have learning and transformational potential for those in housing need at their centre. Consequently, the research translates learning from Bathore, where the practices and experiences of housing have been formed through conditions of protracted scarcity. Through a critical examination of the settling and house-building process, as well as the participatory strategies used in the upgrading programme, the objective of this research is to mobilise learning from Bathore for the Protohome project. In doing so, the research draws from post-colonial scholarship, and activates this through the philosophies and practices of Participatory Action Research. Within this translocal learning process, where knowledge is translated between seemingly different contexts, the research seeks to deconstruct preconceptions about who or where holds the ‘authentic’ knowledge with regards to urban development and housing processes. As a result, in the stories presented here, of designing, building and collaborating, knowledge is deeply embedded in place, people and histories, yet this knowledge can be remapped and used to inform an entirely new context. The research thus moves between the particularities of place and more general observations. It is simultaneously located and dislocated. The translocal lens employed thus goes beyond comparison, it actively tests approaches from one location to the other. Through this translocal learning process the research uncovers how participation in housing may operate as a tool for learning, capacity building and for the creation of new social networks. Yet this is not without the interplay of power. Furthermore this is set within an often obstructive institutional context and an increasingly punitive welfare state, which makes this story complicated and, at times, despondent. However, the research highlights that organised and politicised forms of participation in housing may open up routes for potentially marginalised people to ‘speak to’ and ‘with’ formal institutions of power. In the practical testing of housing approaches on a public-facing live build, the Protohome project not only grounds these conceptual ideas, but also offers an innovative approach to research methodology and dissemination through praxis, which has multi-scalar impacts. On the basis of findings, the thesis tentatively proposes an agenda for ‘participatory housing’, where housing is a route to learning as opposed to an economic product or mere bricks and mortar

The parish churches of Norwich north of the River Wensum: city, community, architecture and antiquarianism

Norwich Ultra Aquam (‘over the water’) formed a discrete leet or administrative area within the medieval city. At its heart was an Anglo-Scandinavian defensive enclosure, with Coslany lying to the west, and later suburban developments to the north and east. Evidence from topographic, dedicatory, archaeological and inter-parochial relationships, suggests that the pattern of church foundation was both complex and distinctive. Unlike several parishes south of the river, there are no indications that the early phases of Ultra Aquam church foundations were the initiative of senior ecclesiastics, or had specifically royal connections. Rather, they were local projects responding to the manner in which the city was developing. Later in the Middle Ages monastic interest on the north bank increased but several of the churches remained in secular hands. Patronage, whether lay or ecclesiastical, played a key part in their architectural development; St Michael Coslany and St George Colegate in particular received considerable burgess investment. The rich antiquarian tradition in the city provides a record of attitudes to the churches in the post-Reformation period which has to be understood in terms of priorities that changed over time

Immunotherapy for Epstein-Barr Virus-Related Lymphomas

Latent EBV infection is associated with several malignancies, including EBV post-transplant lymphoproliferative disorders (LPD), Hodgkin and non-Hodgkin lymphomas, nasopharyngeal carcinoma and Burkitt lymphoma. The range of expression of latent EBV antigens varies in these tumors, which influences how susceptible the tumors are to immunotherapeutic approaches. Tumors expressing type III latency, such as in LPD, express the widest array of EBV antigens making them the most susceptible to immunotherapy. Treatment strategies for EBV-related tumors include restoring normal cellular immunity by adoptive immunotherapy with EBV-specific T cells and targeting the malignant B cells with monoclonal antibodies. We review the current immunotherapies and future studies aimed at targeting EBV antigen expression in these tumors

Evidence for the Presentation of Major Histocompatibility Complex Class I–restricted Epstein-Barr Virus Nuclear Antigen 1 Peptides to CD8+ T Lymphocytes

The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) is expressed in all EBV-associated tumors, making it an important target for immunotherapy. However, evidence for major histocompatibility complex (MHC) class I–restricted EBNA1 peptides endogenously presented by EBV-transformed B and tumor cells remains elusive. Here we describe for the first time the identification of an endogenously processed human histocompatibility leukocyte antigen (HLA)-B8–restricted EBNA1 peptide that is recognized by CD8+ T cells. T cell recognition could be inhibited by the treatment of target cells with proteasome inhibitors that block the MHC class I antigen processing pathway, but not by an inhibitor (chloroquine) of MHC class II antigen processing. We also demonstrate that new protein synthesis is required for the generation of the HLA-B8 epitope for T cell recognition, suggesting that defective ribosomal products (DRiPs) are the major source of T cell epitopes. Experiments with protease inhibitors indicate that some serine proteases may participate in the degradation of EBNA1 DRiPs before they are further processed by proteasomes. These findings not only provide the first evidence of the presentation of an MHC class I–restricted EBNA1 epitope to CD8+ T cells, but also offer new insight into the molecular mechanisms involved in the processing and presentation of EBNA1

Clonal Dynamics In Vivo of Virus Integration Sites of T Cells Expressing a Safety Switch

Safety switches are becoming relevant for the clinical translation of T-cell-based immunotherapies. In patients receiving an allogeneic hematopoietic stem cell transplant, the inducible caspase-9 gene (iC9) safety switch expressed by donor-derived T lymphocytes efficiently controls acute graft versus host disease (GvHD). However, in vivo elimination of iC9-T cells by the chemical inducer of dimerization (CID) that activates the iC9 protein is incomplete. To study this effect, we characterized the clonal diversity and dynamics of vector insertion sites (VIS) in iC9-T cells pre- and post-CID administration in four patients who developed GvHD. We identified 3,203 VIS among four patients and followed their in vivo clonal dynamics up to 161 days post-CID. VIS were categorized by their proximity to host genome elements, gene associations, and cis-modulatory relationship to mapped promoters. We found that VIS are preferentially located near open chromatin and promoter regions; furthermore, there was no evidence for selection bias among VIS surviving the CID treatment. The majority of iC9-T cells with high normalized VIS copy number at the time of GvHD onset were eliminated by CID, while iC9-T cells detectable post-CID generally have low normalized VIS copy number. We propose that suboptimal iC9 transgene expression is responsible for the incomplete elimination of iC9-T cells and illustrate here by simple model how cis-modulatory influences of local genome context and T-cell receptor activation status at time of CID treatment contribute to stochastic sparing of iC9-T cells

Serial Activation of the Inducible Caspase 9 Safety Switch After Human Stem Cell Transplantation

Activation of the inducible caspase 9 (iC9) safety gene by a dimerizing drug (chemical inducer of dimerization (CID) AP1903) effectively resolves the symptoms and signs of graft-versus-host disease (GvHD) in haploidentical stem cell transplant (HSCT) recipients. However, after CID treatment, 1% of iC9-T cells remain and can regrow over time; although these resurgent T cells do not cause recurrent GvHD, it remains unclear whether repeat CID treatments are a safe and feasible way to further deplete residual gene-modified T cells should any other adverse effects associated with them occur. Here, we report a patient who received an infusion of haploidentical iC9-T cells after HSCT and subsequently received three treatments with AP1903. There was a mild (grade 2) and transient pancytopenia following each AP1903 administration but no non-hematological toxicity. Ninety five percent of circulating iC9-T cells (CD3+CD19+) were eliminated after the first AP1903 treatment. Three months later, the residual cells had expanded more than eightfold and had a lower level of iC9 expression. Each repeated AP1903 administration eliminated a diminishing percentage of the residual repopulating cells, but elimination could be enhanced by T-cell activation. These data support the safety and efficiency of repeated CID treatments for persistent or recurring toxicity from T-cell therapies