Project acronym BIOMEMOS
Project Higher order structure and function of biomembranes
Researcher (PI) Poul Nissen
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Advanced Grant (AdG), LS1, ERC-2009-AdG
Summary The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Summary
The biomembrane is a prerequisite of life. It enables the cell to maintain a controlled environment and to establish electrochemical gradients as rapidly accessible energy stores. Biomembranes also provide scaffold for organisation and spatial definition of signal transmission in the cell. Crystal structures of membrane proteins are determined with an increasing pace. Along with functional studies integral studies of individual membrane proteins are now widely implemented. The BIOMEMOS proposal goes a step further and approaches the function of the biomembrane at the higher level of membrane protein complexes. Through a combination of X-ray crystallography, electrophysiology, general biochemistry, biophysics and bioinformatics and including also the application of single-particle cryo-EM and small-angle X-ray scattering, the structure and function of membrane protein complexes of key importance in life will be investigated. The specific targets for investigation in this proposal include: 1) higher-order complexes of P-type ATPase pumps such as signalling complexes of Na+,K+-ATPase, and 2) development of methods for structural studies of membrane protein complexes Based on my unique track record in structural studies of large, difficult structures (ribosomes and membrane proteins) in the setting of a thriving research community in structural biology and biomembrane research in Aarhus provides a critical momentum for a long-term activity. The activity will take advantage of the new possibilities offered by synchrotron sources in Europe. Furthermore, a single-particle cryo-EM research group formed on my initiative in Aarhus, and a well-established small-angle X-ray scattering community provides for an optimal setting through multiple cues in structural biology and functional studies
Max ERC Funding
2 444 180 €
Duration
Start date: 2010-04-01, End date: 2015-03-31
Project acronym VOICE
Project """Hearing voices"" - From cognition to brain systems"
Researcher (PI) Kenneth Hugdahl
Host Institution (HI) UNIVERSITETET I BERGEN
Country Norway
Call Details Advanced Grant (AdG), SH4, ERC-2009-AdG
Summary The experience of "hearing voices", i. e. auditory hallucinations in the absence of an external acoustic input is a perplexing phenomenon. In addition to being a defining characteristic of schizophrenia, experiences of "hearing voices" may be more common in the general population than what we normally think, which poses a theoretical challenge from a neuropsychological point of view. The overall goal is to track auditory hallucinations from the cognitive (phenomenological) to the neuronal (brain systems and synaptic) levels of explanation, by drawing on my previous research on hemispheric asymmetry and attention-modulation of dichotic listening and functional neuroimaging. I now suggest a new model for explaining "hearing voices" in patients and in healthy individuals. From the phenomenology of what patients and healthy individuals "hearing voices" actually report led me to question current models and theories that auditory hallucinations are "inner speech" or "traumatic memories". Since both patients and healthy individuals "hearing voices" subjectively report experiencing someone "speaking to them" it seems that a perceptual model would better fit the actual phenomenology. A perceptual model can however not explain why patients and healthy individuals differ in the way they cope with and interpret the "voice". An expanded model is therefore advanced that sees auditory hallucinations as a break-down of the dynamic interplay between bottom-up (perceptual) and top-down (inhibitory control) cognitive processes. It is suggested that while both groups show deficient perceptual processing, the patients in addition have impaired inhibitory control functions which prevents them from interpreting the "voices" as coming from inner thought processes. A series of experiments are proposed to test the model.
Summary
The experience of "hearing voices", i. e. auditory hallucinations in the absence of an external acoustic input is a perplexing phenomenon. In addition to being a defining characteristic of schizophrenia, experiences of "hearing voices" may be more common in the general population than what we normally think, which poses a theoretical challenge from a neuropsychological point of view. The overall goal is to track auditory hallucinations from the cognitive (phenomenological) to the neuronal (brain systems and synaptic) levels of explanation, by drawing on my previous research on hemispheric asymmetry and attention-modulation of dichotic listening and functional neuroimaging. I now suggest a new model for explaining "hearing voices" in patients and in healthy individuals. From the phenomenology of what patients and healthy individuals "hearing voices" actually report led me to question current models and theories that auditory hallucinations are "inner speech" or "traumatic memories". Since both patients and healthy individuals "hearing voices" subjectively report experiencing someone "speaking to them" it seems that a perceptual model would better fit the actual phenomenology. A perceptual model can however not explain why patients and healthy individuals differ in the way they cope with and interpret the "voice". An expanded model is therefore advanced that sees auditory hallucinations as a break-down of the dynamic interplay between bottom-up (perceptual) and top-down (inhibitory control) cognitive processes. It is suggested that while both groups show deficient perceptual processing, the patients in addition have impaired inhibitory control functions which prevents them from interpreting the "voices" as coming from inner thought processes. A series of experiments are proposed to test the model.
Max ERC Funding
2 281 572 €
Duration
Start date: 2010-07-01, End date: 2015-06-30
