Dissertation

Sensing Transport

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Author: Sijben, H.J.
Date: 23 November 2022
Links: Thesis in Leiden Repository

Due to their critical role in cellular homeostasis, physiological processes and disease development, there is a great number of SLCs that have the potential to be viable drug targets for the treatment of disease. Robust assays are required to identify and characterize potential drugs for SLCs, which are often screened in vitro using cell-based or cell-free systems. Conventional assays either require the use of chemical labels, which i) can be invasive and compromise a cell’s physiology, ii) are based on end-point measurements, iii) use cell preparations and/or iv) do not allow screening of a large number of compounds. This thesis presents the development and application of novel label-free assays based on electrical impedance that allow the assessment of functional activity for three human SLCs: the dopamine transporter (DAT, SLC6A3), norepinephrine transporter (NET, SLC6A2) and excitatory amino acid transporters (EAAT, SLC1 family). With the ability to screen and characterize SLC inhibitors, these assays are a new addition to the ever-expanding toolbox for SLC transporters and could prove valuable in drug discovery programs for a wide range of diseases.