Scientist (f/m) / PhD position Subject: Protein-lipid interactions and the influence of cellular environments on glycosylation processes
The addition of carbohydrates to acceptor molecules is a ubiquitous modification of proteins conserved across all domains of life. Glycosylation events range from the addition of monosaccharides to the attachment of highly complex carbohydrate chains to protein and lipid acceptors. This enormous structural diversity is reflected in the broad range of functions that can be affected by glycosylation, including protein folding, trafficking/localisation and regulation of protein activity. Glycosylation defects such as those that occur in congenital disorders of glycosylation (CDGs) are also expected to direct impact on the lipid composition of membrane domains. In addition to its direct effects on lipid synthesis, aberrant glycosylation can also indirectly affect lipids and lipid signalling. In both cases, altered lipid homeostasis is likely to contribute to the pathophysiology of these multisystemic disorders. Here we aim to investigate the roles of lipids in modulating the assembly, activity and specificity of glycosylation enzymes. We will study whether and how CGDs affect intracellular lipid homeostasis, using different eukaryotic model systems, ranging from human patient fibroblasts to mouse and fish models. Employing quantitative nano-mass spectrometry, we will study lipid pathway alterations in CDG to determine the consequences of hypoglycosylation on cellular lipid homeostasis. In summary, we aim to elucidate the interplay between lipids and glycosylation enzymes and to determine how glycosylation defects affect cellular and organismal lipid homeostasis.


References: Contreras FX, Ernst AM, Haberkant P, Björkholm P, Lindahl E, Gonen B, Tischer C, Elofsson A, von Heijne G, Thiele C, Pepperkok R, Wieland F, Brügger B (2012) Molecular recognition of a single sphingolipid species by a protein's transmembrane domain. Nature 481, 525-529. Brügger B. (2014) Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem 83:79-98. Ernst AM, Brügger B. (2014) Sphingolipids as modulators of membrane proteins. Biochim Biophys Acta 1841:665-70. Methods that will be used: Quantitative lipid mass spectrometry, Bioinformatics, Chemical Biology Cooperation partners: Christian Thiel (Heidelberg University Hospital), Sabine Strahl (COS Heidelberg), Falk Büttner (Hannover Medical School)


Personal qualifications: We seek to recruit a highly motivated student with a strong background in Biochemistry/Chemistry/Biotechnology. You should have analytical skills and an interest in developing and establishing novel mass spec methods. We expect that you can both work independently and as a team player. Excellent written and spoken English skills are mandatory.


Deadline: 18. Jun 2017


Contact details: Brügger, Britta