Physiology and Pathophysiology
At the systemic level, we will elucidate the function of selected SLC26 isoforms in organs where it is poorly understood and has potential clinical relevance. Given the multiple functions presumed for the 10 mammalian isoforms, we will focus on two epithelial organ systems, i.e. intestine and kidney. While allowing for meaningful comparison of mechanisms, this selection should also facilitate the discovery and analysis of general principles. Matching the physiological and pathophysiological expertise of the project leaders, we will examine the function of SLC26A3, A6, and A9 in the gastrointestinal system and the role of SLC26A2 and A11 in renal tubular transport. To address the contribution of SLC26 proteins to ion fluxes and the role of new SLC26 interactors in these organs, we will make use of cutting edge in vitro model systems (intestinal organoids) and novel conditional mouse models. In each case, the strategy also builds upon the generation of new knowledge about cell biology (see 2.) and molecular function (see 1.) and thus involves collaborative work across all levels of biological complexity.