ERC FUNDED PROJECTS

The goal of this proposed research initiative is to engineer chloroplasts into production units for high value bio-active natural products. The first aim is to re-route the biosynthetic pathways for these compounds into the chloroplast and to boost compound formation by optimizing and channeling reducing power from photosystem I into to the energy demanding steps. By these measures we aim to overcome the inherent limitations in plants to channel photosynthetic fixed carbon and reducing power directly into production of desired bioactive natural products. Our production targets are diterpenoids with the anti-cancer drug ingenol-3-angelate and the adenylyl cyclase activator forskolin as the two chosen test compounds. Formation of the complicated hydroxylated core structures of these compounds is catalyzed by diterpenoid synthases and cytochrome P450s. These will be identified and expressed in the chloroplast. The ultimate aim is to construct a single supramolecular enzyme complex effectively using solar energy to produce complex diterpenoids. This will be accomplished by tethering the terpenoid synthases and the key P450 enzymes directly to the photosystem I complex using some of the small membrane spanning subunits of photosystem I as membrane anchors. The experimental systems used will initially be transient expression in tobacco and then move to stably transformed moss (Physcomitrella patens). The production system is built on the “share your parts” principle of synthetic biology and the aim is to construct a modular ‘tool box’ as template for tailoring the synthesis of a whole range of valuable bioactive diterpenoids. Typically, these are difficult to obtain because they are produced in very low amounts in plants difficult to cultivate. The proposal opens up entirely new research horizons and removes current bottlenecks in industrial exploitation. The technology holds the promise of true sustainability as it is driven by solar power and CO2.

2 499 699 €

Start date: 2013-03-01, End date: 2019-02-28

The goals are: 1) to develop a universal laboratory-based 4D X-ray microscope with potentials in the broad field of materials science and beyond; 2) to advance metal research by quantifying local microstructural variations using the new 4D tool and by including the effects hereof in the understanding and modelling of industrially relevant metals. Today, high resolution 4D (x,y,z,time) crystallographic characterization of materials is possible only at large international facilities. This is a serious limitation preventing the common use. The new technique will allow such 4D characterization to be carried out at home laboratories, thereby wide spreading this powerful tool. Whereas current metal research mainly focuses on average properties, local microstructural variations are present in all metals on several length scales, and are often of critical importance for the properties and performance of the metal. In this project, the new technique will be the cornerstone in studies of such variations in three types of metallic materials: 3D printed, multilayered and micrometre-scale metals. Effects of local variations on the subsequent microstructural evolution will be followed during deformation and annealing, i.e. during processes typical for manufacturing, and occurring during in-service operation. Current models largely ignore the presence of local microstructural variations and lack predictive power. Based on the new experimental data, three models operating on different length scales will be improved and combined, namely crystal plasticity finite element, phase field and molecular dynamics models. The main novelty here relates to the full 4D validation of the models, which has not been possible hitherto because of lack of sufficient experimental data. The resulting fundamental understanding of the inherent microstructural variations and the new models are foreseen to be an integral part of the future design of metallic materials for high performance applications.

2 496 519 €

Start date: 2018-10-01, End date: 2023-09-30

This project studies the topic of human consciousness from a multidisciplinary perspective. Human consciousness can be defined as the inner subjective experience of mental states such as perceptions, judgments, thoughts, intentions to act, feelings or desires. These experiences are to be described from a subjective, phenomenal first-person account. On the other hand, cognitive neurosciences explore the neural correlates with respect to brain topology and brain dynamics from an objective third-person account. Despite a great interest in consciousness among cognitive neuroscientists, there are yet no general agreement on definitions or models, and no attempts to draw conclusions from the existing body of work to make progress in the treatment of patients. While it is generally the case that research in cognitive neuroscience has a minimal influence on clinical work in neurorehabilitation, this is very much the case in consciousness studies. Here, so far, there is no direct connection to clinical practice MindRehab will make use of an integrated approach to find new ways to understand cognitive dysfunctions and to actually rehabilitate patients with cognitive problems after brain injury. This integrated approach, using consciousness studies to create progress in a clinical area, is novel and does not exist as an explicit goal for any other research group in the world. The objective of MindRehab is to integrate three aspects: Philosophy and basic research on consciousness, and clinical work in neurorehabilitation. Furthermore, the objective is to realize a number of research projects leading to novel contributions at the frontier of all three domains. However, contrary to all other current research projects in this field, the emphasis is put on the latter the clinical work.

1 641 232 €

Start date: 2010-06-01, End date: 2015-05-31

Several sophisticated image processing circuits have been discovered in the animal retina, many of which manifest massive neural synchrony. A major insight is that this type of synchrony often translates to high-frequency activity on a macroscopic level, but electroretinography (ERG) has not been tapped to examine this potential in humans. Bolstered by our compelling results combining ERG with magnetoencephalography (MEG), this project will address several open questions with respect to human visual processing: 1) Could variable retinal timing be linked to intrinsic image properties and pass on phase variance downstream to visual cortex? Our data suggests the retina responds to moving gratings and natural imagery with non-phase-locked high gamma oscillations (>65 Hz) just like visual cortex, and that slower ERG potentials exhibit strong phase-locking within stimuli but large phase variance across stimuli. 2) Do such retinal gamma band responses, both evoked and induced, directly drive some cortical gamma responses? Pilot data suggests that it can, through retinocortical coherence, our novel ERG-MEG mapping technique. 3) Several kinds of motion have now been shown to elicit massive synchrony in mammalian retina circuits. Does this also result in macroscopic high-frequency activity? If so, our experiments will finally reveal and characterize motion detection by the human retina. 4) Do efferent pathways to the retina exist in humans? We discovered that the ERG exhibits eyes-closed alpha waves strikingly similar to the classic EEG phenomenon and, leveraging our retinocortical coherence technique, that this activity is likely driven by contralateral occipital cortex. Then, can retinal responses be influenced by ongoing cortical activity? Characterizing retinocortical interaction represents a complete paradigm shift that will be imperative for our understanding of neural synchrony in the human nervous system and enable several groundbreaking new avenues for research.

1 499 850 €

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