ERC FUNDED PROJECTS

This proposal outlines a highly ambitious and path-breaking research program. Through a tightly integrated package of basic theoretical work, strategic empirical research projects, international workshops, and a large number of publications in leading journals, the research program seeks to move sociology in a more analytical direction. One part of the research program focuses on the epistemological and methodological foundations of analytical sociology, an approach to sociological theory and research that currently receives considerable attention in the international scholarly community. This work will be organized around two core themes: (1) the principles of mechanism-based explanations and (2) the micro-macro link. The empirical research analyzes in great detail the ethnic, gender, and socio-economic segregation of key interaction domains in Sweden using the approach of analytical sociology. The interaction domains focused upon are schools, workplaces and neighborhoods; domains where people spend a considerable part of their time, where much of the social interaction between people takes place, where identities are formed, and where important resources are distributed. Large-scale longitudinal micro data on the entire Swedish population, unique longitudinal data on social networks within school classes, and various agent-based simulation techniques, are used to better understand the processes through which schools, workplaces and neighborhoods become segregated along various dimensions, how the domains interact with one another, and how the structure and extent of segregation affects diverse social and economic outcomes.

1 745 098 €

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

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity. AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets. We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays. New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging

1 500 000 €

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

Spectroscopic binary stars (SB2s) and in particular spectroscopic eclipsing binaries are one of the most useful objects in astrophysics. Their photometric and spectroscopic observations allow one to determine basic parameters of stars and carry out a wide range of tests of stellar structure, evolution and dynamics. Perhaps somewhat surprisingly, they can also contribute to our understanding of the formation and evolution of (extrasolar) planets. We will study eclipsing binary stars by combining the classic - stellar astronomy - and the modern - extrasolar planets - subjects into a cutting edge project. We propose to search for and subsequently characterize circumbinary planets around ~350 eclipsing SB2s using our own novel cutting edge radial velocity technique for binary stars and a modern version of the photometry based eclipse timing of eclipsing binary stars employing 0.5-m robotic telescopes. We will also derive basic parameters of up to ~700 stars (~350 binaries) with an unprecedented precision. In particular for about 50% of our sample we expect to deliver masses of the components with an accuracy ~10-100 times better than the current state of the art. Our project will provide unique constraints for the theories of planet formation and evolution and an unprecedented in quality set of the basic parameters of stars to test the theories of the stellar structure and evolution.

1 500 000 €

Start date: 2010-12-01, End date: 2016-11-30

There is a large need for revitalization of the research on coronary heart disease (CHD) including: a) improved risk prediction and more adequate individually-tailored treatment; and b) new targets for drug development based on pathways previously unknown to be involved in CHD pathophysiology. The overall goal of this proposal is to improve prevention and treatment of CHD through better understanding of the biology underlying disease development, identification of new biomarkers for improved risk prediction, and discovery of novel targets for drug development. The specific aims are to: 1) Establish and characterize causal genes in known CHD loci (gene regions) through: a) resequencing of known CHD loci; b) expression profiling in liver, arteries, myocardium and skeletal muscle; c) high-throughput protein profiling; and d) experimental follow-up in zebrafish (Danio rerio) models. 2) Discover new proteins, metabolites and pathways involved in CHD pathophysiology using global proteomic and metabolomic profiling to provide new biomarkers and drug targets. We will integrate genomic, transcriptomic, metabolomic and proteomic data from five longitudinal, population-based cohort studies with detailed phenotyping and one study with tissue collections for expression studies. The cohort studies include 36,907 individuals; there are 3,093 prevalent CHD cases at baseline and the estimated number of incident (new) events in previously healthy by 2016 is 2,202. In addition, we work with zebrafish model systems to establish causal CHD genes and characterize their mechanisms of action. We have access to unique study materials, state-of-the art methods, and a strong track record of successful projects in this field. To our knowledge, there are no other groups combining -omics methods to elucidate the whole chain from DNA variation to overt CHD in such large and well-characterized study samples. Further, we are unaware of other groups using zebrafish models to screen for and characterize causal CHD genes. Our work is anticipated to lead to new important insights into the pathophysiology of CHD, identification of new biomarkers for improved risk prediction, and discovery of novel targets for drug development.

1 498 224 €

Start date: 2014-01-01, End date: 2018-12-31

The research I propose here will provide an enabling technology; spatially resolved transcriptomics, to address important problems in cell- and developmental-biology, in particular: How are stem cells in the skin and gut proliferating without turning into cancers? How are differentiated cells related, in their transcriptome and spatial positions, to their progenitors? To investigate these problems on a molecular level and open up paths to find completely new spatiotemporal interdependencies in complex biological systems, I propose to use our newly developed DNA-origami strategy (Benson et al, Nature, 523 p. 441 (2015) ), combined with a combinatorial cloning technique, to build a new method for deep mRNA sequencing of tissue with single-cell resolution. These new types of origami are stable in physiological salt conditions and opens up their use in in-vivo applications. In DNA-origami we can control the exact spatial position of all nucleotides. By folding the scaffold to display sequences for hybridization of fluorophores conjugated to DNA, we can create optical nano-barcodes. By using structures made out of DNA, the patterns of the optical barcodes will be readable both by imaging and by sequencing, thus enabling the creation of a mapping between cell locations in an organ and the mRNA expression of those cells. We will use the method to perform spatially resolved transcriptomics in small organs: the mouse hair follicle, and small intestine crypt, and also perform the procedure for multiple samples collected at different time points. This will enable a high-dimensional data analysis that most likely will expose previously unknown dependencies that would provide completely new knowledge about how these biological systems work. By studying these systems, we will uncover much more information on how stem cells contribute to regeneration, the issue of de-differentiation that is a common theme in these organs and the effect this might have on the origin of cancer.

1 923 263 €

Start date: 2017-08-01, End date: 2022-07-31

This project studies evaluation and valuation as ways of coordinating actors and resources. Valuation is the ascribing of value to people, organizations, things and events given that there is no standard of value. Evaluation is judging according to an already existing value-standard. Valuation and evaluation are ways of ranking and thus ordering of objects . Markets are examples of economic social formations in which valuations and evaluations are the foundation for the choices made. Valuation and evaluation are important means of coordination also outside of the economy, in competitions (e.g., sports), reviews (e.g., books), and auditing (e.g., of ethical conduct). This project is motivated by evaluation and valuation as increasingly influential ways of coordinating social life. Choices based on evaluation have gradually replaced networks and hierarchies as the preferred coordination form, but processes of valuation or evaluation are not well-understood. The overarching research question of this project is: how do processes of coordination based on valuations function? By understanding these processes can we analyze the consequences of coordinated by the means of evaluation in different spheres of life. It is also the foundation for policy suggestions. The proposed project uses theoretical insights about market elements in economics and sociology and on the relational sociological literature on social formations. Empirical sub-projects are designed to facilitate comparison, to establish validated conclusions and to promote theory development. This project opens up a new avenue of research of coordination based on valuation and evaluation. It will lead to the establishment a high quality research group located at the frontiers of social science.

1 476 251 €

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

My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014. The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized. Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.

1 525 000 €

Start date: 2016-03-01, End date: 2021-02-28

In Europe today disabled people comprise some 65 million (10%). Yet they are marginalized in society and research, and little is known on how disabilities become liveable. This project challenges this bias by proposing to investigate ‘liveable disabilities’ as a function of disability and opportunity structures across time. It analyses four life course dimensions: disabled people’s (1) health and well-being; (2) involvement in education and work; (3) in a partner relationship and family; and (4) in leisure structures. Through this I identify liveable disabilities before, during and after the Swedish welfare state. The results are of significant cross-national interest as they form a useful baseline for what constitutes liveable disabilities, which helps governing bodies maximize opportunity structures for disabled people to participate fully in society. This proposal is unique in employing mixed-methods life course research across time. First, it involves quantitative analysis of Sweden’s long-term digitized population databases, which reflect how disability impacts on people’s educational, occupational, marital and survival chances. The statistical outcome is novel in demonstrating how different impairments intersect with human characteristics relative to society’s structures of the past 200 years. Second, qualitative analyses uncover how disabled people today experience and talk about the above dimensions (1-4) themselves, and how mass media depict them. Third, I make innovative studies of leisure structures, which may promote liveable disabilities. The proposal aims to establish me at the forefront of disability research. It benefits from my scholarship in history and demography and from three excellent centres at Umeå University I am connected to, funded by the Swedish Research Council. One centre researches populations, another gender. The third provides expertise in disability studies and ready access to stakeholders outside academia.

1 999 870 €

Start date: 2016-02-01, End date: 2021-01-31

Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that is defective in multiple sclerosis (MS). Although OL precursor cells (OPCs) can initially promote remyelination in MS, this regenerative mechanism eventually fails in progressive MS. OPCs go through several epigenetic states that ultimately define their potential to differentiate and myelinate. OPCs in progressive MS stall in a distinct epigenetic state, incompatible with differentiation and remyelination. We hypothesize that these OPCs regress to an epigenetic state reminiscent of the state of embryonic OPCs, which remain undifferentiated. In this proposal, we aim to uncover the causes behind the remyelination failure upon disease progression in MS. We will determine the epigenetic/transcriptional states of OPCs during development and in MS, using single cell and bulk RNA sequencing and quantitative proteomics. We will further investigate how the interplay between transcription factors (TFs), chromatin modifiers (ChMs) and non-coding RNAs (ncRNAs) contributes to the transition between epigenetic states of OPCs. The results will allow the identification of ChMs and ncRNAs that can modulate these states and thereby control OPC differentiation and myelination. We will use this knowledge to investigate whether we can reverse the epigenetic state of OPCs in MS, in order to promote their differentiation and remyelination. The unique combination of leading-edge techniques such as SILAC coupled with immunoprecipitation and mass-spectrometry, single-cell RNA sequencing, ChIP-Sequencing, among others, will allow us to provide insights into novel epigenetic mechanisms that might be underlying the effects of environmental and lifestyle risk factors for MS. Moreover, this project has the potential to lead to the discovery of new targets for epigenetic-based therapies for MS, which could provide major opportunities for improved clinical outcome of MS patients in the near future.

1 895 155 €

Start date: 2016-09-01, End date: 2021-08-31