ERC FUNDED PROJECTS

Cell volume regulation is crucial for any living cell because changes in volume determine the metabolic activity through e.g. changes in ionic strength, pH, macromolecular crowding and membrane tension. These physical chemical parameters influence interaction rates and affinities of biomolecules, folding rates, and fold stabilities in vivo. Understanding of the underlying volume regulatory mechanisms has immediate application in biotechnology and health, yet these factors are generally ignored in systems analyses of cellular functions. My team has uncovered a number of mechanisms and insights of cell volume regulation. The next step forward is to elucidate how the components of a cell volume regulatory circuit work together and control the physicochemical conditions of the cell. I propose construction of a synthetic cell in which an osmoregulatory transporter and mechanosensitive channel form a minimal volume regulatory network. My group has developed the technology to reconstitute membrane proteins into lipid vesicles (synthetic cells). One of the challenges is to incorporate into the vesicles an efficient pathway for ATP production and maintain energy homeostasis while the load on the system varies. We aim to control the transmembrane flux of osmolytes, which requires elucidation of the molecular mechanism of gating of the osmoregulatory transporter. We will focus on the glycine betaine ABC importer, which is one of the most complex transporters known to date with ten distinct protein domains, transiently interacting with each other. The proposed synthetic metabolic circuit constitutes a fascinating out-of-equilibrium system, allowing us to understand cell volume regulatory mechanisms in a context and at a level of complexity minimally needed for life. Analysis of this circuit will address many outstanding questions and eventually allow us to design more sophisticated vesicular systems with applications, for example as compartmentalized reaction networks.

2 247 231 €

Start date: 2015-07-01, End date: 2020-06-30

AFRIGOS investigates the process of 'respacing' Africa, a political drive towards regional and continental integration, on the one hand, and the re-casting of Africa's engagement with the global economy, on the other. This is reflected in unprecedented levels of investment in physical and communications infrastructure, and the outsourcing of key functions of Customs, Immigration and security agencies. AFRIGOS poses the question of how far respacing is genuinely forging institutions that are facilitating or obstructing the movement of people and goods; that are enabling or preventing urban and border spaces from being more effectively and responsively governed; and that take into account the needs of African populations whose livelihoods are rooted in mobility and informality. The principal research questions are approached through a comparative study of port cities, border towns and other strategic nodes situated along the busiest transport corridors in East, Central, West and Southern Africa. These represent sites of remarkable dynamism and cosmopolitanism, which reflects their role in connecting African urban centres to each other and to other global cities. AFRIGOS considers how governance 'assemblages' are forged at different scales and is explicitly comparative. It works through 5 connected Streams that address specific questions: 1. AGENDA-SETTING is concerned with policy (re-)formulation. 2. PERIPHERAL URBANISM examines governance in border towns and port cities. 3. BORDER WORKERS addresses everyday governance emerging through the interaction of officials and others who make their livelihoods from the border. 4. CONNECTIVE INFRASTRUCTURE looks as the transformative effects of new technologies. 5. PEOPLE & GOODS IN MOTION traces the passage of people and goods and the regimes of regulation to which they are subjected. AFRIGOS contributes to interdisciplinary research on borderland studies, multi-level governance and the everyday state.

2 491 364 €

Start date: 2016-01-01, End date: 2020-12-31

"This project will undertake a transnational, multi-sited ethnographic study of moral and political subjectivity in HIV/AIDS prevention and treatment programs from the perspective of socio-cultural anthropology. The main research question is: what kinds of politico-moral persons are constituted in institutional contexts that combine human rights and personal responsibility approaches to health, and how these kinds of subjectivities relate to local, national, and global forms of the politico-moral represented in health policies? In particular, this research will be carried out in Indonesia (Jakarta and Bali), South Africa (Western Cape), USA (New York City), and various locations throughout Eastern Europe in HIV/AIDS programs and institutions that increasingly combine human rights and personal responsibility approaches to treatment and prevention. This project is the first anthropological research on health governance done on a global scale. Until now most anthropological studies have focused on one health program in one location without simultaneously studying similar processes in comparable contexts in other parts of the world. In contrast, this project will take a global perspective on the relationship between health issues, morality, and governance by doing transnational multi-sited research. This project will significantly contribute to the current anthropological focus on bio-citizenship and push it in new directions, resulting in a new anthropological theory of global bio-political governance and global politico-moral subjectivities. This theory will describe and explain recent transnational processes of shaping particular kinds of politico-moral subjectivities through health initiatives. By doing research in comparable world areas this project will significantly contribute to the development of a theory of politico-moral governance with global reach."

1 499 370 €

Start date: 2012-05-01, End date: 2017-04-30

This four-year interdisciplinary project addresses the question what has been learned through the use of better regulation ? Better regulation is a flagship policy on the Lisbon agenda for growth and jobs. Its aims are to provide new governance architectures for law-making, to increase the competitiveness of the regulatory environment, and to secure wide social legitimacy for multi-level systems of rules. Whilst most of the research has looked at how better regulation is changing, this project will produce findings on what has changed because of better regulation. Theoretically, the project will use (and significantly improve on) theories of policy learning. Empirically, it will cover Denmark, Italy, the Netherlands, Poland, the UK and the EU including multi-level analysis and analysis by sector of regulation. Methodologically, the project will draw on comparative analysis of types of learning, experiments with regulatory policy-makers in six countries and the European Commission, large-n analysis of impact assessments, backward-mapping of legislation (to appraise the role played by better regulation in the formulation or laws in the UK and the EU), meta-analysis of case-studies and co-production of knowledge with better regulation officers. Dissemination will target both stakeholders (i.e., policy officers, civil society organizations, and business federations) and academic conferences in political science, law, and risk analysis, with a major research monograph to be completed in year 4 and a final interdisciplinary conference.

948 448 €

Start date: 2009-09-01, End date: 2013-09-30

This project is a comparative anthropology of conscience, ethics and human rights. Numerous international human rights documents formally declare their commitment to protect freedom of conscience. But, what is conscience and how do we know it when we see it? How do we distinguish it from self-interest or fanaticism? And what happens when the concept, often associated with a distinct Christian or liberal history, travels across cultural boundaries? The project will examine the cultural conditions under which claims to conscience are made possible, and the types of claims that are most persuasive when doing so. The project addresses these issues through the comparative analysis of three case studies: British pacifists, Sri Lankan activists, and Soviet dissidents. These case studies have been carefully chosen to provide globally significant, but contrasting examples of contests over the implications of claims to conscience. If claims of conscience are often associated with a specifically liberal and Christian tradition, mid-twentieth century Britain can be said to stand at the centre of that tradition. Sri Lanka represents a particularly fraught post-colonial South Asian counterpoint, wracked by nationalist violence, and influenced by ethical traditions associated with forms of Hinduism and Buddhism. Soviet Russia represents a further contrast, a totalitarian regime, where atheism was the dominant ethical language. Finally, the project will return specifically to international human rights institutions, examining the history of the category of conscience in the UN human rights system. This project will be ground breaking, employing novel methods and analytical insights, in order to producing the first comparative analysis of the cultural and political salience of claims of conscience. In doing so, the research aims to transform our understandings of the limits and potentials of attempts to protect freedom of conscience.

1 457 869 €

Start date: 2015-08-01, End date: 2020-07-31

This 6-year project aims to co-ordinate field research in each of these fields to elaborate a new model of emplaced human-animal relations evoking recent theoretical concerns of the definition of the person, the attribution of agency, and renewed attention to ‘built environments’. The project will work inductively from empirical observations in seven field sites across the circumpolar Arctic from the Russian Federation, to Fennoscandia, to Canada. The circumpolar Arctic originally provided many of the primary thought experiments for classic models of cultural evolution. It has now again become the focus of powerful debates over the balance between the protection of cultural heritage and the development of natural resources to fuel a future for industrial economies. The human-non-human relationships chosen for study cover the full range of theoretical and political discourse within the sciences today from primary encounters in domination to contemporary bio-technical innovations in farming. The team will transcend typical ‘existential’ models of domination between people and animals by describing complex social settings where more than one species interact with the cultural landscape. The team will also challenge existing definitions between wild and tame by instead examining what links these behaviour types together. Further, the team members will examine how domestication was never a sudden, fleeting intuition but rather a process wherein people and domesticates are sometimes closer and sometimes farther from each other. Finally, the research team, working within the above mentioned literatures, will develop a renewed model – a new way of describing – these relationships which does not necessarily rely upon metaphors of domination, competition, individual struggle, origins, or hybridity. The strength of the team, and the principle investigator, is their demonstrated ability to carry out fieldwork in this often difficult to access region.

2 497 830 €

Start date: 2012-07-01, End date: 2018-06-30

Knowledge is an anthropological constant that is indissociable from the birth and interactions of human societies, but is at best a secondary concern for scholars of international relations and globalization. Contemporary global studies are thus unable to account for the co-constitution of knowledge and politics at a macro-scale, and remain especially blind to the historical patterns of epistemic development that operate at the level of the species as a whole and have shaped its global political history in specific, path-dependent ways up to now. ARTEFACT is the first project to pursue a knowledge-centered investigation of global politics. It is uniquely grounded in an anthropological approach that treats globalization and human knowledges beyond their modern manifestations, from the longue-durée perspective of our species’ social history. 'The global as artefact' is more than a metaphor. It reflects the premise that human collectives 'make' the political world not merely through ideas, language, or norms, but primordially through the material infrastructures, solutions, objects, practices, and skills they develop in response to evolving structural challenges. ARTEFACT takes agriculture as an exemplary and especially timely case-study to illuminate the entangled global histories of knowledge and politics, analyzing and comparing four increasingly inclusive 'global political systems' of the Ancient, Medieval, Modern, and Contemporary eras and their associated agrarian socio-epistemic revolutions. ARTEFACT ultimately aims to 1) develop an original theory of the global, 2) launch Global Knowledge Studies as a new cross-disciplinary domain of systematic empirical and theoretical study, and 3) push the respective boundaries of the anthropology of knowledge, global history, and international theory beyond the state-of-the-art and toward a holistic understanding that can illuminate how past trends of socio-epistemic evolution might shape future paths of global life.

1 428 165 €

Start date: 2017-09-01, End date: 2022-08-31

Life on earth is sustained by the process that converts sunlight energy into chemical energy: photosynthesis. This process is operating near the boundary between life and death: if the absorbed energy exceeds the capacity of the metabolic reactions, it can result in photo-oxidation events that can cause the death of the organism. Over-excitation is happening quite often: oxygenic organisms are exposed to (drastic) changes in environmental conditions (light intensity, light quality and temperature), which influence the physical (light-harvesting) and chemical (enzymatic reactions) parts of the photosynthetic process to a different extent, leading to severe imbalances. However, daily experience tells us that plants are able to deal with most of these situations, surviving and happily growing. How do they manage? The photosynthetic membrane is highly flexible and it is able to change its supramolecular organization and composition and even the function of some of its components on a time scale as fast as a few seconds, thereby regulating the light-harvesting capacity. However, the structural/functional changes in the membrane are far from being fully characterized and the molecular mechanisms of their regulation are far from being understood. This is due to the fact that all these mechanisms require the simultaneous presence of various factors and thus the system should be analyzed at a high level of complexity; however, to obtain molecular details of a very complex system as the thylakoid membrane in action has not been possible so far. Over the last years we have developed and optimized a range of methods that now allow us to take up this challenge. This involves a high level of integration of biological and physical approaches, ranging from plant transformation and in vivo knock out of individual pigments to ultrafast-spectroscopy in a mix that is rather unique for my laboratory and will allow us to unravel the photoprotective mechanisms in algae and plants.

1 696 961 €

Start date: 2011-12-01, End date: 2017-11-30

ATM is the protein kinase that is mutated in the hereditary autosomal recessive disease ataxia telangiectasia (A-T). A-T patients display immune deficiencies, cancer predisposition and radiosensitivity. The molecular role of ATM is to respond to DNA damage by phosphorylating its substrates, thereby promoting repair of damage or arresting the cell cycle. Following the induction of double-strand breaks (DSBs), the NBS1 protein is required for activation of ATM. But ATM can also be activated in the absence of DNA damage. Treatment of cultured cells with hypotonic stress leads to the activation of ATM, presumably due to changes in chromatin structure. We have recently described a second ATM cofactor, ATMIN (ATM INteractor). ATMIN is dispensable for DSBs-induced ATM signalling, but ATM activation following hypotonic stress is mediated by ATMIN. While the biological role of ATM activation by DSBs and NBS1 is well established, the significance, if any, of ATM activation by ATMIN and changes in chromatin was up to now completely enigmatic. ATM is required for class switch recombination (CSR) and the suppression of translocations in B cells. In order to determine whether ATMIN is required for any of the physiological functions of ATM, we generated a conditional knock-out mouse model for ATMIN. ATM signaling was dramatically reduced following osmotic stress in ATMIN-mutant B cells. ATMIN deficiency led to impaired CSR, and consequently ATMIN-mutant mice developed B cell lymphomas. Thus ablation of ATMIN resulted in a severe defect in ATM function. Our data strongly argue for the existence of a second NBS1-independent mode of ATM activation that is physiologically relevant. While a large amount of scientific effort has gone into characterising ATM signaling triggered by DSBs, essentially nothing is known about NBS1-independent ATM signaling. The experiments outlined in this proposal have the aim to identify and understand the molecular pathway of ATMIN-dependent ATM signaling.

1 499 881 €

Start date: 2012-02-01, End date: 2018-01-31