Politics, Poverty and the Church in an Age of Austerity

The ‘Age of Austerity’ has ruptured the social fabric of contemporary Britain. Arising from our three-year Life on the Breadline project, this article represents the first fieldwork-led analysis of the multidimensional nature of austerity-age poverty by academic theologians in the UK. The article analyses the impact that austerity has had on Christian responses to poverty and inequality in the UK. We draw on our six ethnographic case studies and interview responses from over 120 national and regional Church leaders to exemplify the four approaches to the Christian engagement with poverty that we identified during our research: ‘caring’, ‘campaigning and advocacy’, ‘enterprise’ and ‘community building’. We argue that the Church needs to grasp the systemic, multidimensional and violent nature of poverty in order to realise the potential embedded in its extensive social capital and fulfil its goal of ‘transforming structural injustice’. The paper shows that the Church remains nervous of moving beyond welfare-based responses to poverty and suggests that none of the existing approaches can force poverty into retreat until the Church re-imagines itself as a liberative movement that embodies God’s preferential option for the poor in every aspect of its life and practice

Can human pluripotent stem cell-derived cardiomyocytes advance understanding of muscular dystrophies?

Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement

An Investigation of Enzyme/Prodrug Systems for Cancer Gene Therapy

Chemotherapy, radiotherapy and surgery, the current treatments for cancer, cure only fifty percent of patients. Gene therapy, where therapeutic genes are transferred directly to the tumour, offers a new form of cancer treatment. However, gene transfer techniques that are currently available can only achieve gene expression in a small proportion of the tumour cells, and this may hinder many gene therapy approaches. It may therefore be important to select genes for cancer therapy that offer the potential for a significant bystander effect, where cells not expressing the therapeutic gene are killed, as well as targeted cells. At present there appear to be two strategies for cancer gene therapy that achieve bystander killing, and hence require targeted expression in only a proportion of the cells. The first depends on stimulation of the immune system by, for example, expression of specific cytokines that increase proliferation of tumoricidal cells, while the second type of bystander effect is associated with enzyme / prodrug systems, which are the focus of the work described in this thesis. The mechanisms and efficacies of the Herpes Simplex virus thymidine kinase / ganciclovir (tk / GCV), human thymidine phosphorylase / 5'-deoxy-5-fluorouridine (tp / DFUR) and E.coli cytosine deaminase / 5-fluorocytosine (cd / FC) enzyme / prodrug systems have been examined. In culture, each enzyme / prodrug combination induced cell death in tumour cells expressing the suicide gene and, in mixed cultures of cells that do or do not express the gene, death occurred in both cell types, indicative of a bystander effect. With the tk / GCV system, in human and rodent cell lines, a correlation has been demonstrated between the bystander effect and gap junctional intercellular communication (GJIC). When cultures lack GJIC, no bystander effect was observed, but only a low level of communication was required to generate extensive bystander killing. Increased enzyme activity, on the other hand, improved the bystander effect, suggesting that high levels of tk expression will be important. Additionally, it has been shown that transfer of toxic metabolites from tk+ to tk- cells occurs within two hr of GCV application, before degenerative events were detected, indicating that apoptosis is the result, not the cause, of the tk / GCV bystander effect. Three of the cell lines used to investigate the tk / GCV system in culture were also used to examine the bystander effect in experimental tumours in nude mice. A correlation between the bystander effect in culture and in vivo was demonstrated in two of the cell lines but not the third, which suggests that other factors are important in vivo. In the tp / DFUR and cd / FC systems, bystander killing was due to transfer of toxic metabolites through the medium, and did not depend on GJIC or cell-cell contact. Bystander killing seen with these systems was weaker than that seen in the tk / GCV system. Combining the tk / GCV system with the tp / DFUR or cd / FC systems in culture was able to produce more extensive bystander killing than either system separately. The improvement was also observed using a cdtk fusion protein. The results in this thesis suggest that the choice of enzyme / prodrug therapy for cancer will be determined by the characteristics of each tumour. In addition they suggest the use of fusion proteins, to combine therapeutic proteins, warrants further investigation