ERC FUNDED PROJECTS

Antibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies. The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics. To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.

150 000 €

Start date: 2014-09-01, End date: 2015-08-31

Our body is colonized by complex microbial communities (our microbiome) that are most abundant in the intestinal tract where they contribute significantly to our health and disease. It has been established that aberrations in our microbiome are of particular importance in obesity, type 2 diabetes and metabolic syndrome, rapidly growing diseases with a drug market volume of over 5 B$ per year. We have discovered in the ERC project Microbes Inside that a particular bacterium is able to modify the intestinal microbiome and may be used to develop a new approach to treat these and other metabolic diseases. The Proof of Concept project ACOM aims to confirm the commercial and technological feasibility of this approach, consolidate and expand our IP position, and develop a product development plan. These form the elements of a business plan that is expected to result in establishing a spin out company (ACOM).

142 000 €

Start date: 2014-06-01, End date: 2015-05-31

"Digital 3D models are gaining more and more importance in diverse application fields ranging from computer graphics, multimedia and simulation sciences to engineering, architecture, and medicine. Powerful technologies to digitize the 3D shape of real objects and scenes are becoming available even to consumers. However, the raw geometric data emerging from, e.g., 3D scanning or multi-view stereo often lacks a consistent structure and meta-information which are necessary for the effective deployment of such models in sophisticated down-stream applications like animation, simulation, or CAD/CAM that go beyond mere visualization. Our goal is to develop new fundamental algorithms which transform raw geometric input data into augmented 3D models that are equipped with structural meta information such as feature aligned meshes, patch segmentations, local and global geometric constraints, statistical shape variation data, or even procedural descriptions. Our methodological approach is inspired by the human perceptual system that integrates bottom-up (data-driven) and top-down (model-driven) mechanisms in its hierarchical processing. Similarly we combine algorithms operating on different levels of abstraction into reconstruction and modeling networks. Instead of developing an individual solution for each specific application scenario, we create an eco-system of algorithms for automatic processing and interactive design of highly complex 3D models. A key concept is the information flow across all levels of abstraction in a bottom-up as well as top-down fashion. We not only aim at optimizing geometric representations but in fact at bridging the gap between reconstruction and recognition of geometric objects. The results from this project will make it possible to bring 3D models of real world objects into many highly relevant applications in science, industry, and entertainment, greatly reducing the excessive manual effort that is still necessary today."

2 482 000 €

Start date: 2014-03-01, End date: 2019-02-28

"AEROCAT aims at the elucidation of the potential of nanoparticle derived aerogels in catalytic applications. The materials will be produced from a variety of nanoparticles available in colloidal solutions, amongst which are metals and metal oxides. The evolving aerogels are extremely light, highly porous solids and have been demonstrated to exhibit in many cases the important properties of the nanosized objects they consist of instead of simply those of the respective bulk solids. The resulting aerogel materials will be characterized with respect to their morphology and composition and their resulting (electro-)catalytic properties examined in the light of the inherent electronic nature of the nanosized constituents. Using the knowledge gained within the project the aerogel materials will be further re-processed in order to exploit their full potential relevant to catalysis and electrocatalysis. From the vast variety of possible applications of nanoparticle-based hydro- and aerogels like thermoelectrics, LEDs, pollutant clearance, sensorics and others we choose our strictly focused approach (i) due to the paramount importance of catalysis for the Chemical Industry, (ii) because we have successfully studied the Ethanol electrooxidation on a Pd-nanoparticle aerogel, (iii) we have patented on the oxygen reduction reaction in fuel cells with bimetallic aerogels, (iv) and we gained first and extremely promising results on the semi-hydrogenation of Acetylene on a mixed Pd/ZnO-nanoparticle aerogel. With this we are on the forefront of a research field which impact might not be overestimated. We should quickly explore its potentials and transfer on a short track the knowledge gained into pre-industrial testing."

2 194 000 €

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

"By 2040, the European population aged over 60 will rise to 290 million, with those estimated to have dementia to 15.9 million. These dramatic demographic changes will pose huge challenges to health care systems, hence a detailed understanding of age-related cognitive and neurobiological changes is essential for helping elderly populations maintain independence. However, while existing research into cognitive ageing has carefully characterised developmental trajectories of functions such as memory and processing speed, one key cognitive ability that is particularly relevant to everyday functioning has received very little attention: In surveys, elderly people often report substantial declines in navigational abilities such as problems with finding one’s way in a novel environment. Such deficits severely restrict the mobility of elderly people and affect physical activity and social participation, but the underlying behavioural and neuronal mechanisms are poorly understood. In this proposal, I will take a new approach to cognitive ageing that will bridge the gap between animal neurobiology and human cognitive neuroscience. With support from the ERC, I will create a team that will characterise the mechanisms mediating age-related changes in navigational processing in humans. The project will focus on three structures that perform key computations for spatial navigation, form a closely interconnected triadic network, and are particularly sensitive to the ageing process. Crucially, the team will employ an interdisciplinary methodological approach that combines mathematical modelling, brain imaging and innovative data analysis techniques with novel virtual environment technology, which allows for rigorous testing of predictions derived from animal findings. Finally, the proposal also incorporates a translational project aimed at improving spatial mnemonic functioning with a behavioural intervention, which provides a direct test of functional relevance and societal impact."

1 318 990 €

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

"Significant parts of our cultural heritage are produced on the Web, yet only insufficient opportunities exist for accessing and exploring the past of the Web. The ALEXANDRIA project aims to develop models, tools and techniques necessary to archive and index relevant parts of the Web, and to retrieve and explore this information in a meaningful way. While the easy accessibility to the current Web is a good baseline, optimal access to Web archives requires new models and algorithms for retrieval, exploration, and analytics which go far beyond what is needed to access the current state of the Web. This includes taking into account the unique temporal dimension of Web archives, structured semantic information already available on the Web, as well as social media and network information. Within ALEXANDRIA, we will significantly advance semantic and time-based indexing for Web archives using human-compiled knowledge available on the Web, to efficiently index, retrieve and explore information about entities and events from the past. In doing so, we will focus on the concurrent evolution of this knowledge and the Web content to be indexed, and take into account diversity and incompleteness of this knowledge. We will further investigate mixed crowd- and machine-based Web analytics to support long- running and collaborative retrieval and analysis processes on Web archives. Usage of implicit human feedback will be essential to provide better indexing through insights during the analysis process and to better focus harvesting of content. The ALEXANDRIA Testbed will provide an important context for research, exploration and evaluation of the concepts, methods and algorithms developed in this project, and will provide both relevant collections and algorithms that enable further research on and practical application of our research results to existing archives like the Internet Archive, the Internet Memory Foundation and Web archives maintained by European national libraries."

2 493 600 €

Start date: 2014-03-01, End date: 2019-02-28

The proposal is built on the core idea to use an ensemble of multiple level self-organization processes to create a next generation photocatalytic platform that provides unprecedented property and reactivity control. As a main output, the project will yield a novel highly precise combined catalyst/photocatalyst assembly to: 1) provide a massive step ahead in photocatalytic applications such as direct solar hydrogen generation, pollution degradation (incl. CO2 decomposition), N2 fixation, or photocatalytic organic synthesis. It will drastically enhance efficiency and selectivity of photocatalytic reactions, and enable a high number of organic synthetic reactions to be carried out economically (and ecologically) via combined catalytic/photocatalytic pathways. Even more, it will establish an entirely new generation of “100% depoisoning”, anti-aggregation catalysts with substantially enhanced catalyst life-time. For this, a series of self-assembly processes on the mesoscale will be used to create highly uniform arrays of single-catalyst-particle-in-a-single-TiO2-cavity; target is a 100% reliable placement of a single <10 nm particle in a 10 nm cavity. Thus catalytic features of, for example Pt nanoparticles, can ideally interact with the photocatalytic properties of a TiO2 cavity. The cavity will be optimized for optical and electronic properties by doping and band-gap engineering; the geometry will be tuned to the range of a few nm.. This nanoscopic design yields to a radical change in the controllability of length and time-scales (reactant, charge carrier and ionic transport in the substrate) in combined photocatalytic/catalytic reactions. It is of key importance that all nanoscale assembly principles used in this work are scalable and allow to create square meters of nanoscopically ordered catalyst surfaces. We target to demonstrate the feasibility of the implementation of the nanoscale principles in a prototype macroscopic reactor.

2 427 000 €

Start date: 2014-03-01, End date: 2019-02-28

Supramolecular assemblies – formed by the self-assembly of hundreds of protein subunits – are part of bacterial nanomachines involved in key cellular processes. Important examples in pathogenic bacteria are pili and type 3 secretion systems (T3SS) that mediate adhesion to host cells and injection of virulence proteins. Structure determination at atomic resolution of such assemblies by standard techniques such as X-ray crystallography or solution NMR is severely limited: Intact T3SSs or pili cannot be crystallized and are also inherently insoluble. Cryo-electron microscopy techniques have recently made it possible to obtain low- and medium-resolution models, but atomic details have not been accessible at the resolution obtained in these studies, leading sometimes to inaccurate models. I propose to use solid-state NMR (ssNMR) to fill this knowledge-gap. I could recently show that ssNMR on in vitro preparations of Salmonella T3SS needles constitutes a powerful approach to study the structure of this virulence factor. Our integrated approach also included results from electron microscopy and modeling as well as in vivo assays (Loquet et al., Nature 2012). This is the foundation of this application. I propose to extend ssNMR methodology to tackle the structures of even larger or more complex homo-oligomeric assemblies with up to 200 residues per monomeric subunit. We will apply such techniques to address the currently unknown 3D structures of type I pili and cytoskeletal bactofilin filaments. Furthermore, I want to develop strategies to directly study assemblies in a native-like setting. As a first application, I will study the 3D structure of T3SS needles when they are complemented with intact T3SSs purified from Salmonella or Shigella. The ultimate goal of this proposal is to establish ssNMR as a generally applicable method that allows solving the currently unknown structures of bacterial supramolecular assemblies at atomic resolution.

1 456 000 €

Start date: 2014-05-01, End date: 2019-04-30

"One of the greatest challenges these days in condensed matter physics is the fundamental understanding of the mechanisms leading to high-Tc superconductivity and ultimately, as a result of that, the discovery of a material system exhibiting a superconducting state with a transition temperature Tc above room temperature. While several different classes of high-Tc materials have been discovered in the past decades, including the well-known CuO-based superconductors (cuprates) or the more recently discovered class of Fe-based superconductors (pnictides), the mechanisms behind high-Tc superconductivity remain controversial. Up to date, no theory exists which would allow for a rational design of a superconducting material with a transition temperature above room temperature. On the other hand, experiments on rather complex material systems often suffer from material imperfections or from a lack of tunability of materials’ properties within a wide range. Our experimental studies within this project therefore will focus on model-type systems which can be prepared and thoroughly characterized with atomic level precision. The growth of the model-type samples will be controlled vertically one atomic layer at a time and laterally by making use of single-atom manipulation techniques. Atomic-scale characterization at low energy-scales will be performed by low-temperature spin-resolved elastic and inelastic scanning tunnelling microscopy (STM) and spectroscopy (STS) as well as by non-contact atomic force microscopy and spectroscopy based techniques. Transport experiments will be conducted by a four-probe STM setup under well-defined ultra-high vacuum conditions. By having access to the electronic and spin, as well as to the vibrational degrees of freedom down to the atomic level, we hope to be able to identify the nature of and the conditions for inducing superconductivity at high temperatures, which could ultimately lead a knowledge-based design of high-Tc superconductors."

2 170 696 €

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