ERC FUNDED PROJECTS

Serotonin (5-HT) is a central neuromodulator and a major target of therapeutic psychoactive drugs, but relatively little is known about how it modulates information processing in neural circuits. The theory of predictive coding postulates that the brain combines raw bottom-up sensory information with top-down information from internal models to make perceptual inferences about the world. We hypothesize, based on preliminary data and prior literature, that a role of 5-HT in this process is to report prediction errors and promote the suppression and weakening of erroneous internal models. We propose that it does this by inhibiting top-down relative to bottom-up cortical information flow. To test this hypothesis, we propose a set of experiments in mice performing olfactory perceptual tasks. Our specific aims are: (1) We will test whether 5-HT neurons encode sensory prediction errors. (2) We will test their causal role in using predictive cues to guide perceptual decisions. (3) We will characterize how 5-HT influences the encoding of sensory information by neuronal populations in the olfactory cortex and identify the underlying circuitry. (4) Finally, we will map the effects of 5-HT across the whole brain and use this information to target further causal manipulations to specific 5-HT projections. We accomplish these aims using state-of-the-art optogenetic, electrophysiological and imaging techniques (including 9.4T small-animal functional magnetic resonance imaging) as well as psychophysical tasks amenable to quantitative analysis and computational theory. Together, these experiments will tackle multiple facets of an important general computational question, bringing to bear an array of cutting-edge technologies to address with unprecedented mechanistic detail how 5-HT impacts neural coding and perceptual decision-making.

2 486 074 €

Start date: 2016-01-01, End date: 2020-12-31

Plants typically release large quantities of volatiles in response to attack by herbivores or pathogens. I may claim to have contributed to various breakthroughs in this research field, including the discovery that the volatile blends induced by different attackers are astonishingly specific, resulting in characteristic, readily distinguishable odour blends. Using maize as our model plant, I wish to take several leaps forward in our understanding of this signal specificity and use this knowledge to develop sensors for the real-time detection of crop pests and diseases. For this, three interconnected work-packages will aim to: • Develop chemical analytical techniques and statistical models to decipher the odorous vocabulary of plants, and to create a complete inventory of “odour-prints” for a wide range of herbivore-plant and pathogen-plant combinations, including simultaneous infestations. • Develop and optimize nano-mechanical sensors for the detection of specific plant volatile mixtures. For this, we will initially adapt a prototype sensor that has been successfully developed for the detection of cancer-related volatiles in human breath. • Genetically manipulate maize plants to release a unique blend of root-produced volatiles upon herbivory. For this, we will engineer gene cassettes that combine recently identified P450 (CYP) genes from poplar with inducible, root-specific promoters from maize. This will result in maize plants that, in response to pest attack, release easy-to-detect aldoximes and nitriles from their roots. In short, by investigating and manipulating the specificity of inducible odour blends we will generate the necessary knowhow to develop a novel odour-detection device. The envisioned sensor technology will permit real-time monitoring of the pests and enable farmers to apply crop protection treatments at the right time and in the right place.

2 498 086 €

Start date: 2018-09-01, End date: 2023-08-31

Europe sits uncomfortably on the idea that there are no political and cultural alternatives credible enough to respond to the current uneasiness or malaise caused by both a world that is more and more non-European and a Europe that increasingly questions what is European about itself. This project will develop a new grounded theoretical paradigm for contemporary Europe based on two key ideas: the understanding of the world by far exceeds the European understanding of the world; social, political and institutional transformation in Europe may benefit from innovations taking place in regions and countries with which Europe is increasingly interdependent. I will pursue this objective focusing on four main interconnected topics: democratizing democracy, intercultural constitutionalism, the other economy, human rights (right to health in particular). In a sense that the European challenges are unique but, in one way or another, are being experienced in different corners of the world. The novelty resides in bringing new ideas and experiences into the European conversation, show their relevance to our current uncertainties and aspirations and thereby contribute to face them with new intellectual and political resources. The usefulness and relevance of non-European conceptions and experiences un-thinking the conventional knowledge through two epistemological devices I have developed: the ecology of knowledges and intercultural translation. By resorting to them I will show that there are alternatives but they cannot be made credible and powerful if we go on relying on the modes of theoretical and political thinking that have dominated so far. In other words, the claim put forward by and worked through this project is that in Europe we don’t need alternatives but rather an alternative thinking of alternatives.

2 423 140 €

Start date: 2011-07-01, End date: 2016-12-31

Calcium-activated chloride channels (CaCCs) play key roles in a range of physiological processes such as the control of membrane excitability, photoreception and epithelial secretion. Although the importance of these channels has been recognized for more than 30 years their molecular identity remained obscure. The recent discovery of two protein families encoding for CaCCs, Anoctamins and Bestrophins, was a scientific breakthrough that has provided first insight into two novel ion channel architectures. Within this proposal we aim to determine the first high resolution structures of members of both families and study their functional behavior by an interdisciplinary approach combining biochemistry, X-ray crystallography and electrophysiology. The structural investigation of eukaryotic membrane proteins is extremely challenging and will require us to investigate large numbers of candidates to single out family members with superior biochemical properties. During the last year we have made large progress in this direction. By screening numerous eukaryotic Anoctamins and prokaryotic Bestrophins we have identified well-behaved proteins for both families, which were successfully scaled-up and purified. Additional family members will be identified within the course of the project. For these stable proteins we plan to grow crystals diffracting to high resolution and to proceed with structure determination. With first structural information in hand we will perform detailed functional studies using electrophysiology and complementary biophysical techniques to gain mechanistic insight into ion permeation and gating. As the pharmacology of both families is still in its infancy we will in later stages also engage in the identification and characterization of inhibitors and activators of Anoctamins and Bestrophins to open up a field that may ultimately lead to the discovery of novel therapeutic strategies targeting calcium-activated chloride channels.

2 176 000 €

Start date: 2014-02-01, End date: 2020-01-31