Integrated Analysis of Epithelial SLC26 Anion Transporters

DFG Research Unit FOR 5046

From Molecular Structure to Pathophysiology

FOR 5046 leverages a multi-level approach aiming at a comprehensive understanding of the SLC26 anion transporters.

This solute carrier family includes functionally versatile anion transporters present throughout all kingdoms of life.

In humans it is increasingly recognized that the SLC26 proteins constitute one of the fundamental groups of membrane transporters that mediate the transmembrane and transepithelial transport of small anions such as chloride, bicarbonate, or sulfate.

Given the pivotal importance of anion transport across various epithelial organs in ion homeostasis we primarily focus those SLC26 transporters expressed in epithelia.

The human genome encodes ten functional homologs, several of which are causally associated with human diseases, such as chloride losing diarrhea, nephrolithiasis, hypothyroidism, male infertility, skeletal malformation, brain edema, or deafness.

We aim to understand these transporters at the various levels of biological complexity from molecule to organism by bringing together and tightly integrating a set of state-of-the-art technical approaches: from single-particle cryo-EM and molecular dynamics simulations at the structural level, via biophysical methods for functional characterization, proteomics to understand the immediate molecular environment, up to human organoids and mouse models to address pathophysiology.