2021.09576.CBM
Biochemical functional and structural studies of the human norepinephrine transporter
In light of the Scientific Cooperation Agreement between Portugal and Germany, 2022-23, Aldino Viegas has been awarded a Transnational Cooperation research grant - 2021.09576.CBM aiming at developing a protocol for obtaining the human norepinephrine transporter (hNET) protein, and characterise its structure. The project will run together with Manuel Etzkorn, from the Heinrich-Heine-University Düsseldorf, an expert in all fields of NMR spectroscopy, membrane protein production and membrane mimetics.
The human norepinephrine (NE) transporter (hNET) is a membrane protein involved in regulating NE levels in the synaptic cleft, and its dysregulation is linked with several diseases.
This project aims to establish a protocol to express, purify and reconstitute hNET in native-like membrane mimetics, characterise its structure and study its molecular determinants of selectivity and the influence of the membrane environment. Additionally, this proposal aims at building/strengthening academic relations between both groups and relies in the involvement of junior scientists not only to provide a thorough (international) training in state-of-the-art techniques, but also to ensure the transfer of knowledge. This cooperation will benefit both teams, adding important knowhow that can be applied to different research topics and future collaboration projects. To our knowledge the proposed approach has not yet been undertaken. Thus, the work proposed is highly innovative and the expected functional and structural data could accelerate the rational design of hNET-targeted drugs, paving the way to a molecular understanding of ligand transporter interactions.