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Groupleader: Doris Höglinger

Lipid signaling and lysosomal biology 

Group Leader Doris Höglinger

Doris Höglinger

Lipid signaling and lysosomal biology

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Research 


Our group is interested in unravelling the mechanisms behind lipid-mediated signalling events. Certain lipid species, especially ones belonging to the biologically active sphingolipids, are powerful signalling molecules involved in many central processes. Therefore, cells must exert tight control over signalling lipid levels. One control checkpoint is the lysosome; an organelle responsible for the breakdown of cellular material such as proteins, nucleic acid, carbohydrates and lipids.  Specifically, many sphingolipid degrading enzymes are localized in the lysosome and any malfunction in this catabolic cascade leads to devastating pathologies. As many mechanisms of lysosomal lipid homeostasis are still unknown, we are interested in studying the lysosome in general and its role in lipid-mediated signalling in particular.

For example, we are pursuing the following questions:

I. What are the protein effectors of signalling lipids?

We have recently developed novel chemical biology tools which allow the identification of protein interactors of single lipid species and plan to further develop this technology. Applied to disease-relevant lipids such as sphingosine, we hope to gain insight into the mechanisms of lipid-mediated signalling and potentially identify new avenues for treatment.

II. How is lipid transport organized?

It is still unclear how the removal or reuse of the breakdown products upon degradation of complex lipids by lysosomal catabolic enzymes is coordinated. By directly visualizing lipid transport from the lysosome, we aim to uncover the mechanisms responsible for establishing and maintaining routes for lysosomal lipid export.

To achieve these goals, we develop and employ novel chemical biology tools complemented with cell biology studies in mammalian cells. Using lysosomal storage diseases as models, we aim to uncover novel pathways and to advance the concept of the lysosome as a signalling hub.
 

CV 


2005 – 2011       Study of technical chemistry at the Johannes Kepler University Linz
2011 – 2015       PhD at the European Molecular Biology Laboratory (EMBL), Heidelberg
2016 – 2017       Postdoc at the Department of Pharmacology, University of Oxford
April 2017 -        Junior group leader at Heidelberg University Biochemistry Center (BZH)
 

Lab Members 



Pia Hempelmann
postdoc

Lab:Room 324 / Phone: +49 6221 54-4753
Mail:pia.hempelmann@bzh.uni-heidelberg.de

 RoomPhone
LAB 324 +49 6221 54-4753
E-Mail pia.hempelmann@bzh.uni-heidelberg.de
Denisa Jamecna
postdoc

Lab:Room 324 / Phone: +49 6221 54-4753
Mail:denisa.jamecna@bzh.uni-heidelberg.de

 RoomPhone
LAB 324 +49 6221 54-4753
E-Mail denisa.jamecna@bzh.uni-heidelberg.de

Publications 


Cellular cholesterol and how to find it. Cellular cholesterol and how to find it. Biochim Biophys Acta Mol Cell Biol Lipids. 1866(9):158989. https://doi.org/10.1016/j.bbalip.2021.158989 Schoop, V., Martello, A., Eden, E.R., & Höglinger, D. (2021)

The glucosylceramide synthase inhibitor PDMP causes lysosomal lipid accumulation and mTOR inactivation. Int J Mol Sci, 22(13):7065. doi: https://doi.org/10.3390/ijms22137065 Harwig, P. & Höglinger, D. (2021)

Bi- and Trifunctional Lipids for Visualization of Sphingolipid Dynamics within the Cell. Methods Mol Biol, 1949:95-103, doi: 10.1007/978-1-4939-9136-5_8.
Höglinger D. (2019)

NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress. Nat Commun, 10(1):4276, doi: 10.1038/s41467-019-12152-2.
Höglinger D, Burgoyne T, Sanchez-Heras E, Hartwig P, Colaco A, Newton J, Futter C, Spiegel S, Platt F, Eden E. (2019)

A click cage: Organelle-specific uncaging of lipid mes-sengers. Angew Chem Int Ed Engl, 57: 1-6, doi: 10.1002/anie.201807497
Wagner N, Stephan M, Höglinger D, Nadler A. (2018)

Trifunctional lipid probes for comprehensive studies of single lipid species in living cells. PNAS 114; 7; 1566-1571; doi: 10.1073/pnas.1611096114
Höglinger D, Nadler A, Haberkant P, Kirkpatrick J, Schifferer M, Stein F, Hauke S, Porter FD, Schultz C. (2017)

Bifunctional Sphingosine for Cell-Based Analysis of Protein-Sphingolipid Interactions. ACS Chemical Biology 2016 11 (1), 222-230. doi: 10.1021/acschembio.5b00810 Haberkant, P., Stein, F., Höglinger, D., Gerl, M.J., Brügger, B., Van Veldhoven, P.P., Krijgsveld, J., Gavin, A.C., & Schultz, C. (2016)

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway. Wellcome Open Res 1;18; doi: 10.12688/wellcomeopenres.10036.1.
Fineran P, Lloyd-Evans E, Lack NA, Platt N, Davis LC, Morgan AJ, Höglinger D, Tatituri RV, Clark S, Williams IM, Tynan P, Al Eisa N, Nazarova E, Willians A, Galione A, Ory DS, Besra GS, Russell DG, Brenner MB, Sim E, Platt FM. (2016)

Intracellular sphingosine releases calcium from lysosomes. ELife. doi: 10.7554/eLife.10616
Höglinger D, Haberkant P, Aguilera-Romero A, Riezman H, Porter FD, Platt FM, Galione A, Schultz C. (2015)

Caged lipids as tools for investigating cellular signaling. Biochim Biophys Acta 1841; 1085-1096
Höglinger D, Nadler A, Schultz C. (2014)

Collaborations 


André Nadler, MPI-CBG
Emily Eden, University College London
Sarah Spiegel, Virginia Commonwealth University
Alain Townsend, University of Oxford
Min Ae Lee-Kirsch, Universitätsklinikum Dresden
Bengt Belgardt, Deutsches Diabetes-Zentrum

 

Funding 


Deutsche Forschungsgemeinschaft - SFB TRR 83
Deutsche Forschungsgemeinschaft - SFB TRR 186

 

Open Positions 


We are looking for motivated chemists, biochemists, molecular or cell biologists with an interest in lipid signalling and lysosomal biology to join our lab for internship, bachelor, master or PhD projects. We are working at the intersection of chemistry and biology and can offer you an interdisciplinary environment and the use of novel methods in the study of fundamental biological questions.

For more information about current projects and open positions please contact: doris.hoeglinger@bzh.uni-heidelberg.de  

Contact



Heidelberg University
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg

Office:
+49 6221 54-4181
Lab:
+49 6221 54-4753
Fax:
+49 6221 54-4366
E-Mail:
doris.hoeglinger@bzh.uni-heidelberg.de


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