Memory depends on lasting changes in the structure of our brain caused by our experiences. These changes have been tracked to activity-dependent modification of synapses, which form the communication interface between neurons. Synapses grow when they are stimulated the right way and become more sensitive. Our lab investigates the mechanisms that connect strengthening of synapses to biochemical activity induced by synaptic stimulation.
Glutamate receptors are key determinants of the sensitivity of synapses as they sense a common neurotransmitter. These receptors are ligand-gated ion channels that open following neuronal stimulation. In addition to the ion channel, they contain a large intracellular domain. These domains are likely intrinsically disordered meaning that they do not have a fixed tertiary structure. These domains affect the ion channel and the recruitment of receptors to the synapse. It is not clear how this occurs mechanistically. Our lab currently study the intracellular domains of glutamate receptors focusing on their interactions with scaffolding proteins and signalling enzymes.
In our research, we have come across phenomena that could be applied in biotechnology and medicine. We are currently exploring whether membrane-less organelles formed by intrinsically disordered proteins can be used in biotechnology. We are also interested in developing new methods for pharmaceutical intervention based on multivalent protein drugs.
Our group uses a broad range of biophysical and biochemical techniques. Generally, our philosophy is to use the best possible technique for the question at hand – even if it means moving out of our comfort zone. Currently most of our projects study intrinsically disordered proteins, so we use methods appropriate for dynamic molecules including NMR spectroscopy and single-molecule fluorescence spectroscopy.
Magnus Kjærgaard is Affiliated Professor at DANDRITE and Associated Professor at the Department of Molecular Biology and Genetics (MBG). Magnus Kjærgaard is one of six co-PIs in the Center of Excellence “PROMEMO – Proteins in Memory” and is further supported by grants from the Villum and Lundbeck Foundations. The lab is situated at Universitetsbyen 81.