Oliver John Belleza


Supervisor: Harald Sitte, Medical University of Vienna


Start of project: 11.09.2019

Title of the project:  Pharmacological characterization of fluorescent probes for imaging monoamine transporters


Research topic of the Student:

Monoamine transporters can be classified into (1) the high-affinity uptake-1 family, which includes the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT), and (2) the low-affinity, high-capacity uptake-2 family which includes the organic cation transporter 3 (OCT3). These transporters are widely expressed in the central nervous system where they facilitate clearance of their monoamine substrates from the synaptic cleft, therefore regulating neuromodulatory effects. The high-affinity transporters DAT, NET, and SERT are known drug targets for the treatment of mental disorders such as depression and attention-deficit hyperactivity disorder. A variety of psychostimulants and drugs of abuse also elicit their effects primarily through actions on these transporters. Therefore, compounds that can be used as pharmacological tools to investigate the conformation, expression, and activity of these transporters are clinically relevant. One such tool is a fluorescently-labeled probe which can provide direct, visual proof of binding events, protein expression, and cell localization. In this project, ligands with known activity on a transporter (e.g., citalopram on SERT, corticosterone on OCT3) will be functionally tagged with a fluorescent dye to create novel fluorescent probes. Effects of structural modifications to native ligand-protein interactions can be investigated in silico prior to chemical synthesis. These fluorescently-labeled ligands will then be characterized chemically (e.g., fluorescence spectroscopy) and biochemically, using a variety of cell assays (e.g., radiotracer flux experiments), to investigate activity on their respective target transporters. Finally, the probes will be visualized on cells expressing the transporters of interest using fluorescence microscopy. 


Lab Rotation project: "Chemical synthesis and characterization of potential fluorescent substrates and ligands for neurotransmitter transporters", 16.09. - 30.10.2020 

Lab host: Nuno Maulide, University of Vienna

Internship abroad:  "Investigations on the serotonin transporter using novel fluorescent probes", 28.02.-02.09.2022

Host lab: Department of Molecular Pharmacology and Therapeutics, Prof. David Sulzer Lab, Columbia University, New York, USA.


Link to publications by Oliver John Belleza