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LMU MUENCHEN

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Country: Germany
641 Projects, page 1 of 129
  • Funder: EC Project Code: 840741
    Overall Budget: 162,806 EURFunder Contribution: 162,806 EUR

    Biosensors play a crucial role in our everyday lives from health monitoring to disease detection. The rapid advancement of sensing technologies dictates an ever growing need for improved biosensors which are capable to continuously monitor analytes in a single-step process and yield low-cost devices. The performance of many biosensors is, however, limited by the binding strength of their molecular recognition unit which dictates the dynamic range of the sensor and is often tightly connected to the signal transduction unit, i.e. its signal output. In this project, I propose to globally solve this limitation by decoupling the molecular recognition and signal transduction units of the biosensor by exploiting self-assembled and programmable DNA origami nanostructures. This fundamental approach will be demonstrated by the design of a sensitive and tunable biosensor for glucose, whose sensing is of utmost importance for the disease monitoring of diabetic patients. DNA origami will be utilized to precisely position all biosensor elements: multifluorophore FRET pair, which will serve as a signal transduction and amplification unit as well as glucose/galactose binding proteins and glucose functionalities, which will provide a molecular recognition unit. Different biomimicry strategies to tune the useful dynamic range of the biosensors will be evaluated aiming to achieve sensitivity at a physiologically relevant glucose concentration. Finally, the potential to combine these advanced glucose biosensors with low-cost read-out instruments (such as smartphone cameras) will be assessed. The DNA origami glucose sensor proposed here is of great promise for the development of wearable and low-cost glucose sensing devices for diabetes monitoring, which will grow into a large demand in our society. Moreover, it will allow me to merge DNA nanotechnology, molecular biology, spectroscopy and chemistry research, laying the foundations upon which to build my future career in Europe.

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  • Funder: EC Project Code: 101040939
    Overall Budget: 1,500,000 EURFunder Contribution: 1,500,000 EUR

    Existing studies on flood-society relations overwhelmingly concentrate on risk, exposure, vulnerability, damage, loss, and adaptation needs, most of which adopt a negative perspective. The fact that various human societies have well survived and continuously developed in flood prone areas (e.g., coasts, river deltas, flood plains, hilly valleys) is far less studied. Closing this research gap requires a deeper historical perspective to investigate the resilience of human society to floods, i.e., flood resilience and its changes. The Tea-Horse Road (THR) area, a flood hotspot across the mountainous Southeast Tibetan Plateau, is an ideal natural laboratory to study the spatial-temporal dynamics of flood resilience due to its long and uniquely documented history with extensive hazard experiences. STORIES will set up a theoretical framework on the multi-spatial-temporal features of flood resilience at the THR region, which covers the spatial differences (household, community, city and region) over the past 600 years regarding the governance, technology, society, and culture perspectives of flood resilience. A set of quantitative proxy data, historical archives, literature re-analysis, statistical data, observation data and field survey data will be integrated into both the empirical study in the case areas and the agent-based modelling across the cases. Specifically, STORIES aims to 1) establish a theoretical understanding of the spatial-temporal scales of flood resilience; 2) investigate the spatial patterns and temporal evolution of flood resilience at the THR cases; 3) model the spatial-temporal dynamics of flood resilience using agent-based models; 4) transfer and generalize the research findings of the THR cases to the Mekong River Delta and beyond. By doing so, STORIES will present pioneering work to shape the emerging research field of flood resilience, offering new and multi-dimensional knowledge on the dynamic nature of flood-society relations.

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  • Funder: EC Project Code: 715466
    Overall Budget: 1,498,180 EURFunder Contribution: 1,498,180 EUR

    Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism. The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression. I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen. The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.

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  • Funder: EC Project Code: 833613
    Overall Budget: 2,201,880 EURFunder Contribution: 2,201,880 EUR

    Nucleosomes, ~147 base pairs of DNA wrapped around an histone protein octamer, package and protect nuclear DNA but also carry important biological information. The position and composition of nucleosomes along chromosomal DNA is a key element of defining the state and identity of a cell. Chromatin remodellers are ATP dependent molecular machines that position, move or edit nucleosomes in a genome wide manner. Collectively, they shape the nucleosome landscape and play central roles in the maintenance and differentiation of cells, but also in pathological transformations. INO80, a megadalton large remodeller consisting of 15 or more subunits, is involved in replication, gene expression and DNA repair. It models chromatin by positioning barrier nucleosomes around nucleosome free regions, editing nucleosomes and generating nucleosome arrays. However, structural mechanisms for INO80 and other remodelling machines are poorly understood due to their complexity. To provide a comprehensive mechanistic framework, to understand how INO80 senses nucleosome free regions to position barrier nucleosomes and how it generates arrays or senses DNA breaks, I propose a challenging but ground-breaking endeavour using a combination of cryo-EM and functional approaches. We address structures of fungal and human INO80 complexes at promoter regions, on di-nucleosomes and at DNA ends and develop quantitative positioning assays to reveal common and distinct features of shaping chromatin in different species. We also explore cryo-EM as tool towards revealing distinct steps the chemo-mechanical remodelling reactions. The proposed research will help derive fundamental molecular principles underlying the modelling of the nucleosome landscape.

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  • Funder: EC Project Code: 101124282
    Overall Budget: 1,999,250 EURFunder Contribution: 1,999,250 EUR

    With one planet per star on average, planet formation must be a robust process. Yet, surprisingly, we still do not fully understand how planet formation works. Current models for planet formation usually assume pre-existing smooth disks and homogeneously distributed planetesimals of arbitrary composition. In contrast, recent results highlight the crucial role of early stage disk sub-structure, inhomogeneous accretion, and carbon depletion processes on the final planetary systems. Until now, adequate techniques to model these dynamic, complex systems in a computationally cost-efficient way were lacking. The overall aim of EARLYBIRD is therefore to overcome this bottleneck and track the planet-building material and its composition through the initial formation of disks into the populations of planetesimals and planets and to reveal in which ways these processes are observable in older disks and exoplanets. The project concretely will 1) determine the global effects of streamers/sustained infall on early evolution of disks and planet formation, 2) study how outbursts and dust evolution interact and determine the effect of high dust-to-gas ratio infall on planetesimal formation, 3) track compositonal changes (e.g. carbon, CO, water) during planet formation and 4) decipher the observable properties all these scenarios imprint in the distribution and composition of small dust, planetesimals, and planets. Based on my pioneering work on disk particle growth and transport, EARLYBIRD will utilize highly innovative 3D modeling techniques, which are unique in being calibrated against full coagulation models and still are two magnitudes faster than a full solver. The project will thereby not only enable me to fully exploit the information imprinted by the disk formation stages on planet formation, but also pave the way for cost-efficient 3D-modeling of dynamic systems in neighboring fields.

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