Doris Höglinger

Name

Name: Doris Höglinger        
Nationality: Austria

European Molecular Biology Laboratory
Cell Biology and Biophysics Unit
Meyerhofstraße 1
69117 Heidelberg
Germany

Contact details:doris.hoeglinger@embl.de
+49 6221 387 8498

Biosketch

Doris Höglinger was born in Rohrbach, Upper Austria and got her university education from the Johannes-Kepler-University in Linz, Austria. She studied Technical Chemistry / Chemical Engineering and focused her initial research internships (at the Linz Institute for Organic Solar Cells and at the University of South Australia in Adelaide) on the field of Material Sciences / Nanotechnology. During her diploma thesis (titled “Fine adjustment of chemoselective ligations for optimal kinetics”) at the Institute for Biophysics of the University Linz, she got for the first time exposed to the world of chemical biology. She was fascinated by the way chemical tools can be used to answer biological questions and decided to follow up on that interest by joining the group of Carsten Schultz (link) at the European Molecular Biology Laboratory (EMBL) in Heidelberg for a PhD.

This change in field broadened her technical expertise from organic, analytic and physical chemistry techniques to molecular biology and biochemistry methods, mammalian tissue culture and live-cell fluorescence microscopy.

Her Sphingonet project “Chemical methods for manipulating sphingolipid levels in living cells” will be carried out mainly at the EMBL, but Doris will also spend part of her fellowship in Howard Riezman’s group at the University of Geneva to apply these tools to sphingolipid metabolism in yeast and to get familiar with yeast-based methodologies.

In her free time, Doris likes to read or to travel, ideally in combination with hiking, rock-climbing or scuba-diving. She is also interested in marine biology and English literature. 

Project title: Chemical methods for manipulating sphingolipid levels in living cells

Project summary:
Studying lipid-mediated signaling networks poses major challenges: One lipid can be substrate to a variety of metabolic enzymes, giving rise to a range of different, secondary effectors. All of these have distinct functions in regulating cellular responses, depending on their concentration and subcellular localization. Also, it is poorly understood how sphingolipid homeostasis is regulated. Another difficulty is the fact that the primary signaling lipid often generated in a rapid and transient fashion. Therefore, this project aims to develop tools which allow manipulation of the intracellular levels of key intermediates of the sphingolipid metabolism (e.g. ceramide, sphingosine) in a time- and space-resolved manner.

To achieve this, two different, independent approaches are taken:

  1. Synthesis of caged sphingolipid analogues allows the controlled release of the active species after photolytic removal of cage-groups in a specific area of interest (see Figure 1).
  2. Adaptation of a chemical dimerizer system to enable the controlled recruitment of sphingolipid-metabolizing enzymes to membranes. Consequently, addition of a dimerizing agent such as rapamycin will lead to either depletion or enrichment of specific sphingolipids at the targeted organelles (plasma membrane, ER, golgi, mitochondria) as visualized in Figure 2.

Figure 1
Figure 1: Schematic representation of uncaging compounds in living cells.

Figure 2

Figure 2: Rapamycin induced translocation of a protein of interest (POI), e.g. lipid metabolizing enzymes (ceramidase, sphingomyelinase, sphingosine kinase) to membranes.

Both approaches lead to instantaneous changes in sphingolipid levels and thus allow for studying the immediate consequences in the signaling network.
The modulation of sphingolipid pools will be monitored sensors for key intermediates in the sphingolipid metabolism (ceramide, sphingosine) developed within the network.

Supervisors

Carsten Schultz (European Molecular Biology Laboratory, Heidelberg)
Joost Holthuis (University of Osnabrueck, Germany)

Biosketch 1st scientific supervisor:

Carsten Schultz is an interdisciplinary Group Leader and Senior Scientist in the Cell Biology & Biophysics Unit at EMBL Heidelberg, Germany. He and his laboratory are interested in signaling networks activated by G-protein coupled and growth factor receptors. To unravel these complex networks, the lab prepares novel tools to non-invasively manipulate signaling networks and to visualize as many events in intact cells as possible. Carsten Schultz is also interested in better understanding the hereditary disease Cystic Fibrosis and therefore teamed up with Prof. Marcus Mall within the University Heidelberg - EMBL Molecular Medicine Partnership Unit and the German Center for Lung Research (DZL).

He is an editorial board member of Chemistry & Biology, ChemBioChem, ACS Chemical Biology, and Current Methods in Chemical Biology. In 2012 he won the Heidelberg Life Science Award. The SPHINGONET project he is supervising is titled "Chemical methods for manipulating sphingolipid levels in living cells".