Consciousness and mental processes arise from physical and chemical processes in the brain. Understanding how this occurs at the molecular level is one of the grand challenges for science in the 21st century.
Our research investigates the mechanism by which information is encoded into and stored in the physical structure of the brain. The paradigmatic model for molecular memory is synaptic plasticity, where communication across a synapse alters the sensitivity of the synapse. Synaptic plasticity is known to be mediated by neurotransmitter receptors and enzymes in the post-synaptic density. We are studying NMDA-type glutamate receptor, focusing on their intrinsically disordered intra-cellular domains and their involvement in synaptic plasticity.
In the cell, many macromolecules are organised into large complexes. The physical association of molecules alter the equilibrium of e.g. enzyme:substrate interactions by controlling the effective concentration. Despite of its importance, effective concentrations in biomolecular complexes are poorly understood. We develop methods to experimentally determine effective concentrations of biomolecules joined by flexible linkers, and use this data to rationalise how the properties of the linker determine effective concentratio. Our goal is to understand how effective concentrations can direct signalling pathways using kinase-scaffolding proteins.
Our research centers on the biological functions of protein dynamis. Currently, we study two biochemical problems described in more detail below: i) Understanding the role of flexible proteins in the molecular basis of memory and ii) Quantifying and predicting effective cocentrations in supra-molecular complexes. Methodologically, we use whatever methods needed to answer biological question at hand but have a special expertise in solution NMR spectroscopy and single molecule FRET techniques.
Our research is currently supported by the Villum Foundation, Aarhus Institute of Advanced Studies and the Lundbeck Foundation.
