ERC FUNDED PROJECTS

For cells and organisms to survive and propagate, they must accurately pass on their genetic information to the next generation. Errors in this process may arise from spontaneous mistakes in normal cellular metabolism, or from exposure to external agents, such as chemical mutagens and radiation. To protect themselves from the consequences of DNA damage, cells have evolved a vast array of pathways DNA repair mechanisms, each optimised for the resolution of a particular problem. One method of DNA repair, called homologous recombination (HR), involves using intact undamaged DNA sequences as a template to repair the damaged copy. HR is used extensively in meiotic cells to repair DNA breaks that are purposely created by the cell. In this context, HR is not just a repair mechanism, but also a method to drive interaction and genetic exchange between maternally and paternally inherited chromosomes, creating haploid genomes which are chimeras of the parental genetic information. Thus, the study of DNA repair and recombination informs our understanding of mechanisms that maintain genome stability, but which also generate genetic diversity, topics that are as critical to the survival of an individual cell as they are for the evolution and survival of an entire ecosystem. In recent decades a great deal has been learned of the genetic and biochemical control of the DNA repair and recombination mechanism. In general we infer gene function from what happens (or doesn’t happen) when we mutate a pathway of interest, and use biochemistry to test function using surrogate, simplified in vitro assays. Here, to bridge the divide between these classic approaches, I propose to develop biochemical methods using intact chromatin prepared from living cells. I believe that integrating chromatin biochemistry, with cell biology and genome-wide analysis will enable a new mode of scientific investigation, detailing how molecular reactions occur on biologically-relevant chromosomal substrates.

1 747 823 €

Start date: 2013-01-01, End date: 2018-12-31

"The overall aim of this research programme is to uncover how family life courses influence health and well-being in later adulthood, whether family related strengths or disadvantages relevant to health offset or compound socio-economic sources of disadvantage, and the extent to which these associations are influenced by societal factors. An important element will be to consider the role of intergenerational influences, including support flows. The geographical focus will be on Europe and the methodological focus on the advanced quantitative analysis of large scale longitudinal data sets. These data sets, chosen for their complementary strengths, will include both country specific and cross national sources. Three major interlinked strands of work will be undertaken. These will focus on 1) Impacts of parenting and partnership histories on health and mortality in mid and later life. 2) Intergenerational support exchanges: demographic, cultural and policy influences and effects on health of both providers and receivers. 3) An over arching theme to be addressed in the above strands and consolidated in the third is how investments in family and social networks are related to socio-economic disparities in later life health and mortality. The programme is will bring together perspectives from a range of disciplines to address issues of great relevance to current policy challenges in Europe. It is challenging because of the problem of dealing with issues of health selection and possible bias arising from various kinds of missing data which will require methodological care and innovation. Results will contribute to the development of theory, the development of methods and provide substantive knowledge relevant to the health and well-being of older Europeans."

1 423 110 €

Start date: 2013-07-01, End date: 2018-06-30

"One of the greatest contemporary challenges for the social sciences is to understand the human costs of the ongoing financial, economic, and debt crises that began to emerge in Europe in 2007. While much attention has focused on the economic dimensions of recessions in Europe, very little work is being done to analyse the consequences of these events for health and well-being. There are widespread concerns that losses of housing, jobs, and income will have damaging effects on public health. Curiously, however, a growing body of social science research suggests that economic recessions may reduce death rates at a population level, such as by lowering the number of road-traffic injuries, alcohol-related deaths and hospital admissions. Hence, although there is universal agreement that economic shocks will affect health, there is considerable confusion about what the direction of this relationship is. This project aims to understand two interrelated questions: How will the recent economic downturns affect health in Europe? What can be done to mitigate potential negative consequences for health from these economic shocks? To answer these questions, the proposed research will draw on a secondary analysis of longitudinal household datasets and country-level economic and health data to estimate how job loss, poverty, debt, and housing foreclosures affect health. Then, drawing on a conceptual model of ‘resilience’, the project will seek to understand why certain groups have experienced better or worse health outcomes than others in the context of recession. These studies will extend the authors’ initial case studies of mortality in Europe revealing a rapid increase in suicide rates, albeit with marked variations across countries, linked to the financial crises of 2007. The research will have important implications for policymakers seeking to protect health from ongoing economic risks and budget cuts, especially as recovery is projected to evolve slowly over the next decade."

1 358 013 €

Start date: 2013-10-01, End date: 2018-09-30

To date, 12 million children have been orphaned by AIDS, and 70 million more live with AIDS-affected caregivers within sub-Saharan Africa. Our programme of research has demonstrated heightened levels of physical, sexual and emotional abuse amongst children in AIDS-affected families. Despite increasing calls for intervention studies addressing child abuse in the developing world (UN 2008; WHO 2010) no interventions or research have yet targeted this high-risk group of AIDS-affected children. This project will develop and test, using a randomised controlled trial design, an evidence-based intervention to prevent and reduce child abuse within AIDS-affected families in South Africa. The study takes an innovative approach, incorporating a tripartite collaborative process between scientists, policy-makers, and civil society, thus maximising cultural applicability and sustainability. The randomised controlled trial includes 1600 adult and child participants, with wait-list controls and 1-year post-test evaluation in a real-world setting. The research has the key aims of 1) Testing theoretical frameworks of causation and prevention of child abuse in the developing world; 2) Testing the efficacy of an intervention for reducing child abuse; (3) Examining potential intervention moderators and mediators; (4) Testing the feasibility of the intervention when implemented by community volunteers at a low cost; (5) Disseminating results within sub-Saharan Africa to inform policy and programming. This study capitalises on the PI’s position as a scientific advisor to Southern African governments and international NGOs, on the expertise of a senior advisory group of academics and policy-makers, and on an established research team. This research is of immediate necessity in promoting child development within the world pandemic of HIV/AIDS. It also goes beyond the state of the art in innovation, collaboration, and a commitment to the active engagement of science with civil society.

1 460 373 €

Start date: 2013-06-01, End date: 2019-01-31