PhD defence by Akriti Soni

Membrane proteins and their domains: Constructing a toolbox for visualizing plasma membrane proteins in Saccharomyces cerevisiae

The frequency of fungal infections is rising while the treatment options are dwindling with an increasing number of drug-resistant fungal species. Ergosterol, the predominant sterol in fungal plasma membranes, is a common target for anti-fungal compounds. Sterol synthesis is an oxygen-dependent process, but during anaerobic conditions, the average cell growth is supported by the uptake of exogenous sterols, for example, serum cholesterol from the host organisms by fungal pathogens.

In Saccharomyces cerevisiae, two ABC transporters, Aus1p and Pdr11p, are responsible for the uptake of exogenous sterol to help assist the normal growth of budding yeast. Localisation studies on Aus1p in Candia albicans, an opportunistic fungus, have shown this transporter to localise in a plasma membrane domain enriched with sterol and sphingolipids. 

Through this study, we attempt to generate a toolbox that can help identify the presence of membrane domains in budding yeast under anaerobic conditions while using Aus1p and Pdr11p as the membrane targets. Studying these proteins enables us to determine their exact domain of localisation in the membrane and potentially their interacting partners, which could serve as new targets for developing new and improved anti-fungal compounds.

Supervisors
Associate Prof. Rosa Lopez Marques, PLEN
Prof. Thomas Günther Pomorski, Ruhr-Universitaet Bochum

Assessment committee
Prof. Dr. Alexander Schulz, Section for Transport Biology, University of Copenhagen
Prof. Dr. Robert Ernst, Universitaet des Saarlandes, Center for Molecular Signaling (PZMS), Medical Biochemistry & Molecular Biology
Prof. Dr. Michael Hollmann, Lehrstuhl Biochemie I – Rezeptorbiochemie, Fakultaet fuer Chemie und Biochemie, Ruhr-Universitaet Bochum