ERC Advanced Grants

Professor Harald Stenmark

Faculty of Medicine, Centre for Cancer Cell Reprogramming

Project: Coincidence detection of proteins and lipids in regulation of cellular membrane dynamics (CODE)

Summary

Duration: Start date: 2019-01-01, End date: 2023-12-31

Call: LS3, ERC-201-ADG

Summary: Specific recruitment of different proteins to distinct intracellular membranes is fundamental in the biology of eukaryotic cells, but the molecular basis for specificity is incompletely understood. This proposal investigates the hypothesis that coincidence detection of proteins and lipids constitutes a major mechanism for specific recruitment of proteins to intracellular membranes in order to control cellular membrane dynamics. CODE will establish and validate Mathematical models for coincidence detection, identify and functionally characterise novel coincidence detectors, and engineer artificial coincidence detectors as novel tools in cell biology and biotechnology.

 

 

 

 

Professor Jukka Corander

Faculty of Medicine, Institute of Basic Medical Sciences

Project: SCARABEE, calable inference algorithms for Bayesian evolutionary epidemiology

Summary

Duration: Start date: 2017-05-01, End date: 2022-04-30

Call: LS6, ERC-2016-ADG

Summary: Advances in sequencing technologies are currently providing an unprecedented opportunity to a detailed discovery of the mechanisms involved in the evolution and spread of microbes causing human infectious disease. Simultaneously the developers of statistical methods face an enormous challenge to cope with the wealth of data brought by this opportunity. We have very recently demonstrated the ability of our advanced computational approaches to deliver breakthroughs in understanding pathogen evolution and transmission in numerous highlight results published in Science, PNAS and topranking Nature journals. The rise of microbial Big Data gives a promise of a giant leap in making causal discoveries, however, the existing statistical methods are neither able to cope with the size and complexity of the emerging data sets nor designed to answer the novel biological questions they enable. To fulfil the promise of giant leaps SCARABEE will leverage scalable inference methods by a unique combination of machine learning algorithms and Bayesian statistical models for evolutionary epidemiology. We focus on central biological questions about adaptation, epistasis, genome evolution and transmission of microbes causing infectious disease. The Big Data combined with the novel inference methods will make it possible to answer a multitude of important questions that remain currently intractable. Through our close collaboration With the leading research centres in infectious disease epidemiology and genomics we expect the SCARABEE project to considerably advance understanding of the evolution and transmission of numerous pathogens that pose a major threat to human health, which will be important for reducing their disease burden in the future. Large-scale biological data will be used to benchmark the developed methods, which will be made publicly available as free software packages to benefit the wide community of microbiologists and infectious disease epidemiologists.

 

Professor Bjørn Jamtveit

Faculty of Mathematics and Natural Sciences, Department of Geosciences

Project: DIME: Disequilibirum metamorphism of stressed lithosphere

Summary

Duration: Start date: 2015-09-01, End date: 2020-08-31

Call: PE10, ERC-2014-ADG

Summary: Most changes in mineralogy, density, and rheology of the Earth’s lithosphere take place by metamorphism, whereby rocks evolve through interactions between minerals and fluids. These changes are coupled with a large range of geodynamic processes and they have first order effects on the global geochemical cycles of a large number of elements. In the presence of fluids, metamorphic reactions are fast compared to tectonically induced changes in pressure and temperature. Hence, during fluid-producing metamorphism, rocks evolve through near-equilibrium states. However, much of the Earth’s lower and middle crust, and a significant fraction of the upper mantle do not contain free fluids. These parts of the lithosphere exist in a metastable state and are mechanically strong. When subject to changing temperature and pressure conditions at plate boundaries or elsewhere, these rocks do not react until exposed to externally derived fluids. Metamorphism of such rocks consumes fluids, and takes place far from equilibrium through a complex coupling between fluid migration, chemical reactions, and deformation processes. This disequilibrium metamorphism is characterized by fast reaction rates, release of large amounts of energy in the form of heat and work, and a strong coupling to far-field tectonic stress. Our overarching goal is to provide the first quantitative physics-based model of disequilibrium metamorphism that properly connects fluid-rock interactions at the micro and nano-meter scale to lithosphere scale stresses. This model will include quantification of the forces required to squeeze fluids out of grain-grain contacts for geologically relevant materials (Objective 1), a new experimentally based model describing how the progress of volatilization reactions depends on tectonic stress (Objective 2), and testing of this model by analyzing the kinetics of a natural serpentinization process through the Oman Ophiolite Drilling Project.

 

Professor Ragnar Winther

Faculty of Mathematics and Natural Sciences, Department of Mathematics

Project: FEEC-A: Finite Element Exterior Calculus and Applications

Summary

Duration: Start date: 2014-02-01, End date: 2019-01-31

Call: PE1, ERC-2013-ADG

Summary: The finite element method is one of the most successful techniques for designing numerical methods for systems of partial differential equations (PDEs). It is not only a methodology for developing numerical algorithms, but also a mathematical framework in which to explore their behaviour. The finite element exterior calculus (FEEC) provides a new structure that produces a deeper understanding of the finite element method and its connections to the partial differential equation being approximated. The goal is to develop discretizations which are compatible with the geometric, topological, and algebraic structures which underlie well-posedness of the partial differential equation. The phrase FEEC was first used in a paper the PI wrote for Acta Numerica in 2006, together with his coworkers, D.N. Arnold and R.S. Falk. The general philosophy of FEEC has led to the design of new algorithms and software developments, also in areas beyond the direct application of the theory. The present project will be devoted to further development of the foundations of FEEC, and to direct or indirect use of FEEC in specific applications. The ambition is to set the scene for a nubmer of new research directions based on FEEC by giving ground-braking contributions to its foundation. The aim is also to use FEEC as a tool, or a guideline, to extend the foundation of numerical PDEs to a variety of problems for which this foundation does not exist. The more application oriented parts of the project includes topics like numerical methods for elasticity, its generalizations to more general models in materials science such as viscoelasticity, poroelasticity, and liquid crystals, and the applications of these models to CO2 storage and deformations of the spinal cord.

 

Professor Øystein Kravdal (participant)

Faculty of Social Sciences, Department of Economics

Project: FAMHEALTH: Family life courses, intergenerational exchanges and later life health

PI: Professor Emily Marjatta Dorothea Grundy at the London School of Economics and Political Science (LSE)

Summary

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

Call: SH3, ERC-2012-ADG

Summary: 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.

 

Professor Christoph Gradmann (participant)

Institute of Health and Society, Faculty of Medicine

Project: GLOBHEALTH: From International Public Health to Global Health

PI: Professor Jean-Paul Gaudilliere, Institut National De La Sante Et De La Recherche Medicale (Inserm)

Summary

Duration: Start date: 2014-08-01, End date: 2019-07-31

Call: SH3, ERC-2013-ADG

Summary: This project aims at a socio-historical study of the transition between the two regimes of knowledge and action, which have characterized the government of health after World War II: the regime of international public health, dominating during the first decades of the postwar era, which was centered on eradication policies, nation-states and international UN organizations; the present regime of global health, which emerged in the 1980s and is centered on risk management and chronic diseases, market-driven regulations, and private-public alliances.
The project seeks to understand this transition in terms of globalization processes, looking at the making of knowledge, the production and commercialization of health goods, the implementation of public health programs, and routine medical work. It will focus on four fields of investigations: tuberculosis, mental health, traditional medicine and medical genetics in order to understand how categories, standardized treatment regimens, industrial products, management tools or specific specialties have become elements in the global government of health. The project associates historical and anthropological investigations of practices in both international and local sites with strong interests in: a) the changing roles of WHO; b) the developments taking place in non-Western countries, India in the first place.
The expected benefits of this research strategy are: a) to take into account social worlds including laboratories, hospitals, enterprises, public health institutions and international organizations; b) to approach the global as something translated in and emerging from local practices and local knowledge; c) to explore different levels of circulations beyond the classical question of North-South transfers; d) to deepen our understanding of the transition from the political and economical order of the Cold War into a neo-liberal and multi-centric age of uncertainty.

 

Researcher Barbara Bramanti

Faculty of Mathematics and Natural Sciences, Centre for Ecological and Evolutionary Synthesis

Project: MEDPLAG: The medieval plagues: ecology, transmission modalities and routes of the infections

Summary

Duration: Start date: 2013-06-01, End date: 2018-05-31

Call:  SH6, ERC-2012-ADG

Summary: The history of late medieval and early modern Europe was deeply affected by epidemics of plague that repeatedly broke out until 1750 AD and caused devastation and death with severe social, political and economic consequences. For decades, historians and scientists have been interested in the ancient pestilences and disputed their origin and epidemiology. One century ago, Yersinia pestis was identified as the causative agent of the current-day pandemic. Only some months ago the MedPlag team conclusively established (Haensch et al. 2010) that this bacterium was responsible for the Black Death (1346-1353 AD) and that two distinct variants of Y. pestis were simultaneously circulating through Europe during this pandemic. These results raise questions concerning the historic Y. pestis strains, their geographical origin, and whether they might have re-circulated in Europe over four centuries or were constantly reintroduced from elsewhere. Other open questions concern the routes of transmission of the medieval plagues and the role played by trade and pilgrimages in their dissemination, the mechanisms of transmission and the implication of wild and anthropochorous fauna, and the interplay between climatic conditions and plague dynamics. In addition, whether the reason for the disappearance of plague from Europe 250 years ago was due to improved hygiene or to genetic or environmental change remains unknown. Finally, while historians and scientists have speculated on the microbe responsible for the Justinian plague (541-542 AD) molecular evidence is still lacking. In this proposal, I outline the methodology by which I will answer these major questions with an inter-domain investigation involving ancient DNA, climatology, ecology, and history. The results of this work will not only settle century-old controversies by giving us valuable information about the past, but also furnish a paradigm for understanding the modality of serious epidemics in Europe; past, present, and future.

 

Professor Kjetil Storesletten

Faculty of Social Sciences, Department of Economics

Project: MACROINEQUALITY: The Macroeconomics of Inequality, Development and the Welfare State

Summary

Duration: Start date: 2013-06-01, End date: 2018-05-31

Call: SH1, ERC-2012-ADG

Summary: This project will develop macro models with heterogeneity across people and firms to understand the consequences of two profound macro trends: the economic transformation of China and the rising cross-sectional inequality in many countries. The ultimate aim is to help these models become everyday tools in macro, development/labour economics, and actual policy making. Inequality and human capital accumulation is an important theme. I will develop tractable models of the equity-efficiency tradeoffs under risk and imperfect financial markets. Due to novel general equilibrium effects, progressive taxation is particularly distortive for education choices. This calls for complementary policies. I also explore the nexus between inequality and aggregate risk, the interaction between inequality and the dynamics of political conflict, and the puzzling success of the Scandinavian welfare model. The project will provide sharper tools for policy analysis. A key aim is to integrate models of mistakes into structural macro models. While such models generally assume rationality, welfare programs are often geared to precisely address negative consequences of human errors. Assuming information is costly, I will quantify bounds on rationality to match observed behaviour. The framework has a wide range of potential uses. I will use it to reevaluate government programs. A large part of the project focuses on China. The rapid economic transformation of emerging economies has raised many new questions for economic theory and policy. I will marshal the use of models with heterogeneity to address these issues. A key goal is to develop a quantitative structural model that can become the benchmark model of fiscal policy analysis and long-run forecasts in China. As an application, I will study cost and gains of various redistribution programs. The project also aims at examining the sources of growth and inflation in China and, ultimately, understanding the culprit of the Chinese growth miracle.

 

Professor Andreas Max Kääb

Faculty of Mathematics and Natural Sciences, Department of Geosciences

Project: ICEMASS: Global Glacier Mass Continuity

Summary

Duration: Start date: 2013-03-01, End date: 2018-02-28

Call: PE10, ERC-2012-ADG

Summary: For the first time in history satellite data and respective archive holdings are now sufficient in terms of their spatial and temporal resolution, and their accuracy, to measure volume changes, velocities and changes in these velocities over time for glaciers and ice caps other than ice sheets on a global scale. The ICEMASS project will derive and analyse glacier thickness changes using satellite laser and radar altimetry, and satellite-derived and other digital elevation models, and convert these to a global glacier mass budget. Such data set will enable major steps forward in glacier and Earth science, in particular: constrain current sea-level contribution from glaciers; complete climate change patterns as reflected in glacier mass changes; quantify the contribution of glacier imbalance to river run-off; allow to separate glacier mass loss from other components of gravity changes as detected through satellite gravimetry; and allow improved modelling of the isostatic uplift component due to current changes in glacier load. These results will be connected to global-scale glacier dynamics, for which a global set of repeat optical and radar satellite images will be processed to measure displacements due to glacier flow and their annual to decadal-scale changes. The analysis of these data will enable several major steps forward in glacier and Earth science, in particular: progress the understanding of glacier response to climate and its changes; provide new insights in processes underlying spatio-temporal variability and instability of glacier flow on decadal scales; improve understanding of dynamic thickness change effects; allow estimating global calving fluxes; progress understanding of transport in glaciers and their role in landscape development; and help to better assess potentially hazardous glacier lakes.

 

Professor Thomas Hylland Eriksen

Faculty of Social Sciences, Department of Social Anthropology

Project: OVERHEATING: The three crises of globalisation: An anthropological history of the early 21st century

Summary

Duration: Start date: 2012-07-01, End date: 2017-06-30

Call: SH3, ERC-2011-ADG

Summary: The research literature on various dimensions of globalisation is enormous, yet this project constitutes the first major attempt to weave disparate empirical strands together within a shared conceptual framework, namely that of crises resulting from the acceleration and intensification of global processes. Three major crises of globalisation are to be explored and analysed. In the realm of environmental issues/climate change, the quest for transnational legal arrangements ensuring sustainability is counteracted by continued growth in the factors leading to environmental crises. In the financial and economic realm, the vulnerability of the global system became apparent during the recent financial crisis, which continues to send ripples through economies worldwide. In the area of culture contact and cultural sustainability, tensions and frictions with strong elements of identity politics intensify owing to increased interaction and resource competition, at the same time as calls for cosmopolitan values and universalization of human rights constitute attempts to overcome conflicts. A key term is sustainability in the sense of reproductive capability, and the main research question is to what extent contemporary world society is sustainable in relation to the three crises and their internal dialectics. The project will entail in-depth ethnographic studies, global surveys (drawing chiefly on extant research literature) and comparison. It will result in two Ph D dissertations, academic articles (written by postdoctoral fellows) and a major monograph, as well as an edited volume, academic articles and a book for a general audience, all written by the PI. This interdisciplinary and comparative project, based mainly on anthropological approaches, aims to build theory and analyse empirical processes shedding light on, and creating a fuller understanding of, the transitions characterising the present world. The intellectual and societal relevance is potentially huge.

 

Professor Mats Carlsson

Faculty of Mathematics and Natural Sciences, Institute of Theoretical Astrophysics

Project: CHROMPHYS: Physics of the Solar Chromosphere

Summary

Duration: Start date: 2012-01-01, End date: 2016-12-31

Call: PE9, ERC-2011-ADG

Summary: CHROMPHYS aims at a breakthrough in our understanding of the solar chromosphere by combining the development of sophisticated radiation-magnetohydrodynamic simulations with observations from the upcoming NASA SMEX mission Interface Region Imaging Spectrograph (IRIS). The enigmatic chromosphere is the transition between the solar surface and the eruptive outer solar atmosphere. The chromosphere harbours and constrains the mass and energy loading processes that define the heating of the corona, the acceleration and the composition of the solar wind, and the energetics and triggering of solar outbursts (filament eruptions, flares, coronal mass ejections) that govern near-Earth space weather and affect mankind's technological environment. CHROMPHYS targets the following fundamental physics questions about the chromospheric role in the mass and energy loading of the corona: - Which types of non-thermal energy dominate in the chromosphere and beyond? - How does the chromosphere regulate mass and energy supply to the corona and the solar wind? - How do magnetic flux and matter rise through the chromosphere? - How does the chromosphere affect the free magnetic energy loading that leads to solar eruptions? CHROMPHYS proposes to answer these by producing a new, physics based vista of the chromosphere through a three-fold effort: - develop the techniques of high-resolution numerical MHD physics to the level needed to realistically predict and analyse small-scale chromospheric structure and dynamics, - optimise and calibrate diverse observational diagnostics by synthesizing these in detail from the simulations, and - obtain and analyse data from IRIS using these diagnostics complemented by data from other space missions and the best solar telescopes on the ground.

 

Professor Andreas Føllesdal

Faculty of Law, Centre for the Study of the Legitimate Roles of the Judiciary in the Global Order

Project: MULTIRIGHTS: The Legitimacy of Multi-level Human Rights Judiciary

Summary

Duration: Start date: 2011-06-01, End date: 2016-05-31

Call: SH2, ERC-2010-AdG

Summary: The proliferation of human rights treaties at regional and global levels may offer moral foundations for international law. However, many worry that this growth of supervisory organs is illegitimate. Consider, for instance - The European Court of Human Rights (ECtHR) is overburdened. - The human rights organs may disagree e.g. on how to balance freedom of expression against protection from hate speech. Which should be obeyed- - Citizens of well-functioning democracies ask: why should such international organs intervene- The MultiRights team of international lawyers and political theorists will first scrutinize the claims of legitimacy deficits. We then consider reform proposals for global and European human rights organs: We develop four plausible models, ranging from Primacy of National Courts to a World Court of Human Rights. We will assess the models by four Contested Constitutional Principles of legitimacy, revised for our multilevel legal order: Human Rights values, the Rule of Law, Subsidiarity, and Democracy. MultiRights thereby provides reasoned comparative assessment of models for human rights regime reforms, and contributes to better standards of legitimacy for international institutions. The findings also help us understand and assess the alleged 'Constitutionalisation of International Law- - an urgent topic under globalization, when governance beyond states increases in density and impact. The academic contributions of MultiRights will also benefit several reforms: - the Interlaken Process on how to improve the ECtHR, - the accession of the EU to the European Convention on Human Rights under the Lisbon Treaty, - the UN Secretary General-s calls to reform the Human Rights treaty body system, and - challenges to the democratic credentials of such human rights review.

 

Professor Trond Helge Torsvik

Faculty of Mathematics and Natural Sciences, Center for Earth Evolution and Dynamics

Project: BPT: Beyond Plate Tectonics

Summary

Duration: Start date: 2011-05-01, End date: 2016-04-30

Call: PE10, ERC-2010-AdG

Summary: Plate tectonics characterises the complex and dynamic evolution of the outer shell of the Earth in terms of rigid plates. These tectonic plates overlie and interact with the Earth's mantle, which is slowly convecting owing to energy released by the decay of radioactive nuclides in the Earth's interior. Even though links between mantle convection and plate tectonics are becoming more evident, notably through subsurface tomographic images, advances in mineral physics and improved absolute plate motion reference frames, there is still no generally accepted mechanism that consistently explains plate tectonics and mantle convection in one framework. We will integrate plate tectonics into mantle dynamics and develop a theory that explains plate motions quantitatively and dynamically. This requires consistent and detailed reconstructions of plate motions through time (Objective 1). A new model of plate kinematics will be linked to the mantle with the aid of a new global reference frame based on moving hotspots and on palaeomagnetic data. The global reference frame will be corrected for true polar wander in order to develop a global plate motion reference frame with respect to the mantle back to Pangea (ca. 320 million years) and possibly Gondwana assembly (ca. 550 million years). The resulting plate reconstructions will constitute the input to subduction models that are meant to test the consistency between the reference frame and subduction histories. The final outcome will be a novel global subduction reference frame, to be used to unravel links between the surface and deep Earth (Objective 2).

 

Professor Ludvig Magne Sollid

Faculty of Medicine, Centre for Immune Regulation

Project: AUTO-CD: Coeliac Disease: Understanding How a Foreign Protein Drives Autoantibody Formation

Summary

Duration: Start date: 2011-05-01, End date: 2017-04-30

Call: LS6, ERC-2010-AdG

Summary: The goal of this project is to understand the mechanism of how highly disease specific autoantibodies are generated in response to the exposure to a foreign antigen. IgA autoantibodies reactive with the enzyme transglutaminase 2 (TG2) are typical of coeliac disease (CD). These antibodies are only present in subjects who are HLA-DQ2 or -DQ8, and their production is dependent on dietary gluten exposure. This suggests that CD4+ gluten reactive T cells, which are found in CD patients and which recognise gluten peptides deamidated by TG2 in context of DQ2 or DQ8, are implicated in the generation of these autoantibodies. Many small intestinal IgA+ plasma cells express membrane Ig hence allowing isolation of antigen specific cells. Whereas control subjects lack anti-TG2 IgA+ plasma cells, on average 10% of the plasma cells of CD patients are specific for TG2. We have sorted single TG2 reactive IgA+ plasma cells, cloned their VH and VL genes and expressed recombinant mAbs. So far we have expressed 26 TG2 specific mAbs. There is a strong bias for VH5-51 usage, and surprisingly the antibodies are modestly mutated. TG2 acts on specific glutamine residues and can either crosslink these to other proteins (transamidation) or hydrolyse the glutamine to a glutamate (deamidation). None of the 18 mAbs tested affected either transamidation or deamidation leading us to hypothesise that retained crosslinking ability of TG2 when bound to membrane Ig of B cells is an integral part of the anti-TG2 response. Four models of how activation of TG2 specific B cells is facilitated by TG2 crosslinking and the help of gluten reactive CD4 T cells are proposed. These four models will be extensively tested including doing in vivo assays with a newly generated transgenic anti-TG2 immunoglobulin knock-in mouse model.

 

Professor Trygve Helgaker

Faculty of Mathematics and Natural Science, Department of Chemistry

Project: ABACUS: Ab-initio adiabatic-connection curves for density-functional analysis and construction

Summary

Duration: Start date: 2011-03-01, End date: 2016-02-29

Call: PE4, ERC-2010-AdG

Summary: Quantum chemistry provides two approaches to molecular electronic-structure calculations: the systematically refinable but expensive many-body wave-function methods and the inexpensive but not systematically refinable Kohn Sham method of density-functional theory (DFT). The accuracy of Kohn Sham calculations is determined by the quality of the exchange correlation functional, from which the effects of exchange and correlation among the electrons are extracted using the density rather than the wave function. However, the exact exchange correlation functional is unknown—instead, many approximate forms have been developed, by fitting to experimental data or by satisfying exact relations. Here, a new approach to density-functional analysis and construction is proposed: the Lieb variation principle, usually regarded as conceptually important but impracticable. By invoking the Lieb principle, it becomes possible to approach the development of approximate functionals in a novel manner, being directly guided by the behaviour of exact functional, accurately calculated for a wide variety of chemical systems. In particular, this principle will be used to calculate ab-initio adiabatic connection curves, studying the exchange correlation functional for a fixed density as the electronic interactions are turned on from zero to one. Pilot calculations have indicated the feasibility of this approach in simple cases—here, a comprehensive set of adiabatic-connection curves will be generated and utilized for calibration, construction, and analysis of density functionals, the objective being to produce improved functionals for Kohn Sham calculations by modelling or fitting such curves. The ABACUS approach will be particularly important in cases where little experimental information is available—for example, for understanding and modelling the behaviour of the exchange correlation functional in electromagnetic fields.

 

Professor Harald Alfred Stenmark

Faculty of Medicine, Centre for Cancer Biomedicine

Project: PI3K-III COMPLEX: The PI3K-III complex: Function in cell regulation and tumour suppression

Summary

Duration: Start date: 2010-01-01, End date: 2014-12-31

Call:  LS3, ERC-2008-AdG

Summary: Phosphoinositides (PIs), phosphorylated derivatives of phosphatidylinositol (PtdIns), control cellular functions through recruitment of cytosolic proteins to specific membranes. Among the kinases involved in PI generation, the PI3K-III complex, which catalyzes conversion of PtdIns into PtdIns 3-phosphate (PI3P), is of great interest for several reasons. Firstly, it is required for three topologically related membrane involution processes - the biogenesis of multivesicular endosomes, autophagy, and cytokinesis. Secondly, through its catalytic product this protein complex mediates anti-apoptotic and antiproliferative signalling. Thirdly, several subunits of the PI3K-III complex are known tumour suppressors, making the PI3K-III complex a possible target for cancer therapy and diagnostics. This proposal aims to undertake a systematic analysis of the PI3K-III complex and its functions, and the following key questions will be addressed: How is the PI3K-III complex recruited to specific membranes? How does it control membrane involution and signal transduction? By which mechanisms do subunits of this protein complex serve as tumour suppressors? The project will be divided into seven subprojects, which include (1) characterization of the PI3K-III complex, (2) detection of the PI3K-III product PI3P in cells and tissues, (3) the function of the PI3K-III complex in downregulation of growth factor receptors, (4) the function of the PI3K-III complex in autophagy, (5) the function of the PI3K-III complex in cytokinesis, (6) the function of the PI3K-III complex in cell signalling, and (7) dissecting the tumour suppressor activities of the PI3K-III complex. The analyses will range from protein biochemistry to development of novel imaging probes, siRNA screens for novel PI3P effectors, functional characterization of PI3K-III subunits and PI3P effectors in cell culture models, and tumour suppressor analyses in novel Drosophila models.

 

Professor Bernt Øksendal

Faculty of Mathematics and Natural Sciences, Department of Mathematics

Project: INNOSTOCH: Innovations in stochastic analysis and applications with emphasis on stochastic control and information

Summary

Duration: Start date: 2009-09-01, End date: 2014-08-31

Call: PE1, ERC-2008-AdG

Summary: For almost all kinds of dynamic systems modeling real processes in nature or society, most of the mathematical models we can formulate are - at best - inaccurate, and subject to random fluctuations and other types of "noise". Therefore it is important to be able to deal with such noisy models in a mathematically rigorous way. This rigorous theory is stochastic analysis. Theoretical progress in stochastic analysis will lead to new and improved applications in a wide range of fields. The main purpose of this proposal is to establish a research environment which enhances the creation of new ideas and methods in the research of stochastic analysis and its applications. The emphasis is more on innovation, new models and challenges in the research frontiers, rather than small variations and minor improvements of already established theories and results. We will concentrate on applications in finance and biology, but the theoretical results may as well apply to several other areas. Utilizing recent results and achievements by PI and a large group of distinguished coworkers, the natural extensions from the present knowledge is to concentrate on the mathematical theory of the interplay between stochastic analysis, stochastic control and information. More precisely, we have ambitions to make fundamental progress in the general theory of stochastic control of random systems and applications in finance and biology, and the explicit relation between the optimal performance and the amount of information available to the controller. Explicit examples of special interest include optimal control under partial or delayed information, and optimal control under inside or advanced information. A success of the present proposal will represent a substantial breakthrough, and in turn bring us a significant step forward in our attempts to understand various aspects of the world better, and it will help us to find optimal, sustainable ways to influence it."

Published Dec. 9, 2015 8:57 AM - Last modified June 8, 2018 11:00 AM