ERC FUNDED PROJECTS

The purpose of this project is to develop new methods for solving boundary value problems (BVPs) for nonlinear integrable partial differential equations (PDEs). Integrable PDEs can be analyzed by means of the Inverse Scattering Transform, whose introduction was one of the most important developments in the theory of nonlinear PDEs in the 20th century. Until the 1990s the inverse scattering methodology was pursued almost entirely for pure initial-value problems. However, in many laboratory and field situations, the solution is generated by what corresponds to the imposition of boundary conditions rather than initial conditions. Thus, an understanding of BVPs is crucial. In an exciting sequence of events taking place in the last two decades, new tools have become available to deal with BVPs for integrable PDEs. Although some important issues have already been resolved, several major problems remain open. The aim of this project is to solve a number of these open problems and to find solutions of BVPs which were heretofore not solvable. More precisely, the proposal has eight objectives: 1. Develop methods for solving problems with time-periodic boundary conditions. 2. Answer some long-standing open questions raised by series of wave-tank experiments 35 years ago. 3. Develop a new approach for the study of space-periodic solutions. 4. Develop new approaches for the analysis of BVPs for equations with 3 x 3-matrix Lax pairs. 5. Derive new asymptotic formulas by using a nonlinear version of the steepest descent method. 6. Construct disk and disk/black-hole solutions of the stationary axisymmetric Einstein equations. 7. Solve a BVP in Einstein's theory of relativity describing two colliding gravitational waves. 8. Extend the above methods to BVPs in higher dimensions.

2 000 000 €

Start date: 2016-05-01, End date: 2022-02-28

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

Mitochondria are required to convert food into usable energy forms and every cell contains thousands of them. Unlike most other cellular compartments, mitochondria have their own genomes (mtDNA) that encode for 13 of the about 90 proteins present in the respiratory chain. All proteins necessary for mtDNA replication, as well as transcription and translation of mtDNA-encoded genes, are encoded in the nucleus. Mutations in nuclear-encoded proteins required for mtDNA maintenance is an important cause of neurodegeneration and muscle diseases. The common result of these defects is either mtDNA depletion or accumulation of multiple deletions of mtDNA in postmitotic tissues. The long-term goal (or vision) of research in my laboratory is to understand in molecular detail how mtDNA is replicated and how this process is regulated in mammalian cells. To this end we use a protein biochemistry approach, which we combine with in vivo verification in cell lines. My group was in 2004 the first to reconstitute mtDNA replication in vitro and we have continued to develop even more elaborate system ever since. In the current application, the major focus is studies of the mitochondrial D-loop region, a triple-stranded structure in the mitochondrial genome. The D-loop functions as a regulatory hub and we will determine how initiation and termination of mtDNA replication is controlled from this region. We will also determine the physical organization of the mtDNA replication machinery at the replication fork and establish how mtDNA deletions, a classical hallmark of human ageing, are formed.

1 999 985 €

Start date: 2016-11-01, End date: 2021-10-31

Pollinator declines in response to land-use intensification have raised concern about the persistence of plant species dependent on insect pollination, in particular by bees, for their reproduction. Recent empirical studies show that reduced pollinator abundance decreases densities of seedlings of insect-pollinated plants and thereby changes the composition of grassland plant communities. Cascading effects on ecosystem functioning and associated organisms are expected, but to which extent and under which conditions this is the case is yet unexplored. Here, I propose a bold, multi-year, landscape-scale experimental assessment of the extent of pollinator-driven plant community changes, their consequences for associated organisms and important ecosystem functions, and their likely contingency on other factors (soil fertility, herbivory). Specifically I will: (1) Set up a network of long-term research plots in landscapes differing in pollinator abundance to measure the changes in plant reproduction over successive years, and assessing experimentally how herbivory and soil fertility mediate these effects. (2) Explore the individual processes linking pollinators, plant communities and ecosystem functioning using long-term experiments controlling pollinator, herbivore and nutrient availability, focusing on a sample of plant species covering both the dominant species and a diversity of functional traits. (3) Assess the context-dependence of pollinator-mediated plant community determination by building and applying process-based models based on observational and experimental data, and combine with existing spatially-explicit pollinator models to demonstrate the applicability to assess agri-environmental measures. This powerful blend of complementary approaches will for the first time shed light on the cornerstone role of this major mutualism in maintaining diverse communities and the functions they support, and pinpoint the risks threatening them and the need for mitigation.

1 998 842 €

Start date: 2019-09-01, End date: 2024-08-31