We continuously work towards higher resolution, better quantification and around bleaching limits, through technological breakthroughs and in a tight colaboration with the Karolinska Institute.
A new role for an old enzyme
Na,K-ATPase as a signal transducer: Na,K-ATPase (NKA) is, in addition to its well known function as an ion transporter, also a signal transducer. When activated by ouabain, or other ligands, it binds to the inositol 1,4, 5 triphosphate receptor (IP3R), triggers intracellular calcium oscillations, activates NF-κB, increases BclxL expression and protects from apoptosis. Other downstream effects include stimulation of cell proliferation. Low doses of ouabain are found to protect from renal damage in rat models of kidney disease and from adverse developmental programming of rat embryonic kidney. Current projects range from studies of intra-molecular allosteric modulation of the NKA catalytic subunit, to mouse models of interrupted NKA-IP3R interaction and rat and mouse models of renal disease. Signaling function and downstream effects of a novel neuron specific ligands are examined in hippocampus.
Dynamics of postsynaptic G protein coupled receptors
The transport of receptors to and from synapses is an important determinant of neuronal plasticity. We study the transport of G-protein coupled receptors (GPCR) and their interaction with other dendritic proteins in hippocampus and striatal neurons. GPCRs are mainly transported via lateral diffusion in the plasma membrane, which is by far the most energy efficient way of transport, but there are exceptional GPCRs, that are transported via intracellular vesicles and inserted in the membrane following neuronal activity. Trapping in the synapse is generally associated with interaction with other proteins, which may also act as allosteric modulators. Techniques include FRAP recording of bulk transport in the plasma membrane, single molecule tracking with quantum dots, use of pHluorin constructs for recording of membrane insertion and STED microscopy for high resolution studies of spine proteins.
Astrocyte function in brain homeostasis
Role in health and disease: It is becoming increasingly clear that astrocytes, the most abundant cell type in the brain, play a significant role in the homeostasis and function of the CNS and that most brain activities should be considered as collaboration between astrocytes and neurons. We study the regulation of ion- and water homeostasis and the metabolism in astrocytes, including the dynamic regulation of the astrocyte water channel aquaporin 4. Current projects involve studies of astrocyte functions implicated in brain disease processes such as brain edema, brain injury and gliomas with the goal to discover new therapeutic targets in the treatment of conditions where astrocyte dysfunction could be a primary or a secondary event.