The structural basis for the function of the human dopamine transporter
Name of applicant
Claus Juul Løland
Title
Professor
Institution
University of Copenhagen
Amount
DKK 1,069,602
Year
2023
Type of grant
Research Infrastructure
What?
When an experience is pleasant it is because the brain’s reward center releases dopamine. The dopamine signal motivates us to do it again. Wrongly regulated dopamine can lead to addiction. This is seen with cocaine which works by blocking the dopamine transporter (DAT) causing a massive increase in dopamine. However, the exact mechanism behind cocaine binding to DAT is currently unclear.
Why?
With the current project, we wish to elucidate the molecular mechanisms behind the transport of dopamine by DAT. We will monitor how DAT is able to grasp dopamine from the outside and sequester it on the inside of the neuron. We will also investigate how the transport mechanism can be halted by inhibitors.
How?
We will use the world’s most powerful microscope. It enables the visualization of the individual atoms. Not all atoms are visible in each molecule, but if you put millions of individual DAT molecules under the microscope, the small contribution from each can, trough terabytes of data and massive computer power, be stacked and combined to visualize one averaged DAT molecule of atomic resolution.