Research

Research in my lab is focussed on structural and/or biological questions that can be solved by Nuclear Magnetic Resonance.  In parallel, we additionally employ a diverse range of biochemical, biomolecular and bioinformatics techniques to develop a comprehensive understanding of the studied systems.

Structural Biology

To understand cellular processes on a molecular level the 3D structures of the respective proteins have to be known. NMR spectroscopy is a versatile technique both for elaborate structure determination and for fast interaction studies e.g. for ligand screening. It is also possible to determine dynamical aspects of the studied systems at atomic resolution. We have studied a diverse range of proteins with the aim to understand how protein function is related to structure and dynamics. Current main activities of my lab center on the interplay between structure and dynamics of γ-secretase substrates, topic of the DFG funded research group FOR2290 “Understanding intramembrane proteolysis”. The intramembrane protease γ-secretase is a key player in Aβ plaque generation that occurs during Alzheimer’s disease. Studies of my lab suggest that substrate recognition is linked to the pliability of the transmembrane helices (Silber et al. 2020).

Fig 1: Docking of the structural bundle of APP-TM into a model of presenilin, the catalytic unit of γ-secretase.  

Metabolomics

Metabolites are products of cellular processes that are found in organisms and body fluids. The composition of the metabolome, the sum of all metabolites, varies with many factors like the developmental state of the organism, malnutrition or disease.

We employ NMR spectroscopy paired with statistical analyses to investigate body fluids like urine or blood or extracts of cells or whole organs. In this way, we determine the chemical fingerprint of the studied systems. Our aim is to develop diagnostic tools for disease recognition or for studying the effect of chemicals or drugs on the organism. As a non-targeted approach, all sufficiently concentrated metabolites with hydrogen atoms contribute to the data.

In this way, we explored markers for acute kidney disease in children (Muhle-Goll et al. 2020) or how well blood metabolites are removed by hemodialysis (Kromke et al. 2016).

We collaborate with biologists and clinicians at KIT and the university of Heidelberg (https://www.3dmattermadetoorder.kit.edu/), who  provide us with the biological and medical samples . E.g. we currently work on the identification of specific metabolites that may govern derivation of retinal organoids (https://www.3dmattermadetoorder.kit.edu/phds_771.php)

Publications


2021
Delavault, A.; Opochenska, O.; Laneque, L.; Soergel, H.; Muhle-Goll, C.; u. a.
Lipase-Catalyzed Production of Sorbitol Laurate in a “2-in-1” Deep Eutectic System: Factors Affecting the Synthesis and Scalability.
2021. Molecules, 26 (9), 2759. doi:10.3390/molecules26092759
2020
Spitz, C.; Schlosser, C.; Guschtschin-Schmidt, N.; Stelzer, W.; Muhle-Goll, C.; u. a.
Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix.
2020. iScience, 23 (12), Article: 101775. doi:10.1016/j.isci.2020.101775
Sternberg, U.; Tzvetkova, P.; Muhle-Goll, C.
The simulation of NMR data of flexible molecules: sagittamide A as an example for MD simulations with orientational constraints.
2020. Physical chemistry, chemical physics, 22 (30), 17375–17384. doi:10.1039/d0cp01905d
Silber, M.; Hitzenberger, M.; Zacharias, M.; Muhle-Goll, C.
Altered Hinge Conformations in APP Transmembrane Helix Mutants May Affect Enzyme-Substrate Interactions of γ-Secretase.
2020. ACS chemical neuroscience, 11 (24), 4426–4433. doi:10.1021/acschemneuro.0c00640
Muhle-Goll, C.; Eisenmann, P.; Luy, B.; Kölker, S.; Tönshoff, B.; u. a.
Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study.
2020. International journal of molecular sciences, 21 (4), Article No.1187. doi:10.3390/ijms21041187
2019
Götz, A.; Högel, P.; Silber, M.; Chaitoglou, I.; Muhle-Goll, C.; u. a.
Increased H-Bond Stability Relates to Altered ε-Cleavage Efficiency and Aβ Levels in the I45T Familial Alzheimer’s Disease Mutant of APP.
2019. Scientific reports, 9 (1), 5321. doi:10.1038/s41598-019-41766-1
Götz, A.; Mylonas, N.; Högel, P.; Silber, M.; Muhle-Goll, C.; u. a.
Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.
2019. Biophysical journal, 116 (11), 2103–2120. doi:10.1016/j.bpj.2019.04.030
Hauser, A.; Eisenmann, P.; Muhle-Goll, C.; Luy, B.; Dötsch, A.; u. a.
Efficient Extraction from Mice Feces for NMR Metabolomics Measurements with Special Emphasis on SCFAs.
2019. Metabolites, 9 (3), Article: 55. doi:10.3390/metabo9030055
2018
Straub, B.; Andexer, J. N.; Arenz, C.; Beifuss, U.; Muhle-Goll, C.; u. a.
Trendbericht Organische Chemie 2017.
2018. Nachrichten aus der Chemie, 66 (3), 249–280. doi:10.1002/nadc.20184072148
Siebenhaller, S.; Gentes, J.; Infantes, A.; Muhle-Goll, C.; Kirschhöfer, F.; u. a.
Lipase-Catalyzed Synthesis of Sugar Esters in Honey and Agave Syrup.
2018. Frontiers in Chemistry, 6, Article: 24. doi:10.3389/fchem.2018.00024
Siebenhaller, S.; Kirchhoff, J.; Kirschhöfer, F.; Brenner-Weiß, G.; Muhle-Goll, C.; u. a.
Integrated Process for the Enzymatic Production of Fatty Acid Sugar Esters Completely Based on Lignocellulosic Substrates.
2018. Frontiers in Chemistry, 6, Article: 421. doi:10.3389/fchem.2018.00421
2017
Siebenhaller, S.; Hajek, T.; Muhle-Goll, C.; Himmelsbach, M.; Luy, B.; u. a.
Beechwood carbohydrates for enzymatic synthesis of sustainable glycolipids.
2017. Bioresources and Bioprocessing, 4 (1), Art.Nr. 25. doi:10.1186/s40643-017-0155-7
Cato, L.; Neeb, A.; Sharp, A.; Buzón, V.; Muhle-Goll, C.; u. a.
Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.
2017. eLife, 6, Art.Nr. e27159. doi:10.7554/eLife.27159
Straub, B. F.; Andexer, J.; Arenz, C.; Beifuss, U.; Muhle-Goll, C.; u. a.
Organische Chemie 2016.
2017. Nachrichten aus der Chemie, 65 (3), 266–304. doi:10.1002/nadc.20174059831
Siebenhaller, S.; Muhle-Goll, C.; Luy, B.; Kirschhöfer, F.; Brenner-Weiss, G.; u. a.
Sustainable enzymatic synthesis of glycolipids in a deep eutectic solvent system.
2017. Journal of molecular catalysis / B, 133, 281–287. doi:10.1016/j.molcatb.2017.01.015
Mack, C.; Wefers, D.; Schuster, P.; Weinert, C. H.; Muhle-Goll, C.; u. a.
Untargeted multi-platform analysis of the metabolome and the non-starch polysaccharides of kiwifruit during postharvest ripening.
2017. Postharvest biology and technology, 125, 65–76. doi:10.1016/j.postharvbio.2016.10.011
2016
Itzen, A.; Schaschke, N.; Beifuss, U.; Lehmann, M.; Muhle-Goll, C.; u. a.
Organische Chemie.
2016. Nachrichten aus der Chemie, 64 (3), 255–294. doi:10.1002/nadc.20164047492
Eisenmann, P.; Ehlers, M.; Weinert, C. H.; Tzvetkova, P.; Muhle-Goll, C.; u. a.
Untargeted NMR Spectroscopic Analysis of the Metabolic Variety of New Apple Cultivars.
2016. Metabolites, 6 (3), 29. doi:10.3390/metabo6030029
Kromke, M.; Palomino-Schätzlein, M.; Pfeffer, S.; Pineda-Lucena, A.; Muhle-Goll, C.; u. a.
Profiling human blood serum metabolites by nuclear magnetic resonance spectroscopy: a comprehensive tool for the evaluation of hemodialysis efficiency.
2016. Translational research, 171, 71–82.e9. doi:10.1016/j.trsl.2016.02.003
Leiter, A.; Rau, S.; Winger, S.; Muhle-Goll, C.; Luy, B.; u. a.
Influence of heating temperature, pressure and pH on recrystallization inhibition activity of antifreeze protein type III.
2016. Journal of food engineering, 187, 53–61. doi:10.1016/j.jfoodeng.2016.04.019
2015
Kudryavtsev, K.; Ivantcova, P. M.; Muhle-Goll, C.; Churakov, A. V.; Sokolov, M. N.; u. a.
Menthols as Chiral Auxiliaries for Asymmetric Cycloadditive Oligomerization: Syntheses and Studies of β-Proline Hexamers.
2015. Organic Letters, 17 (24), 6178–6181. doi:10.1021/acs.orglett.5b03154
Kügler, J. H.; Muhle-Goll, C.; Hansen, S. H.; Völp, A. R.; Kirschhöfer, F.; u. a.
Glycolipids produced by Rouxiella sp. DSM 100043 and isolation of the biosurfactants via foam-fractionation.
2015. AMB express, 5 (1), 82/1–11. doi:10.1186/s13568-015-0167-7
Muhle-Goll, C.; Luy, B.
Organische Chemie 2014 (Trendbericht).
2015. Nachrichten aus der Chemie, 63, 266–305. doi:10.1002/nadc.201590092
Tussing, S.; Greb, L.; Tamke, S.; Schirmer, B.; Muhle-Goll, C.; u. a.
Autoinduced catalysis and inverse equilibrium isotope effect in the frustrated Lewis pair catalyzed hydrogenation of imines.
2015. Chemistry - a European journal, 21, 8056–8059. doi:10.1002/chem.201500805
Kügler, J. H.; Kraft, A.; Heißler, S.; Muhle-Goll, C.; Luy, B.; u. a.
Extracellular aromatic biosurfactant produced by Tsukamurella pseudospumae and T. spumae during growth on n-hexadecane.
2015. Journal of Biotechnology, 211, 107–114. doi:10.1016/j.jbiotec.2015.06.424
Pöhnlein, M.; Ulrich, J.; Kirschhöfer, F.; Nusser, M.; Muhle-Goll, C.; u. a.
Lipase-catalyzed synthesis of glucose-6-O-hexanoate in deep eutectic solvents.
2015. European journal of lipid science and technology, 117 (2), 161–166. doi:10.1002/ejlt.201400459
2014
Aberle, D.; Muhle-Goll, C.; Bürck, J.; Wolf, M.; Reißer, S.; u. a.
Structure of the Membrane Anchor of Pestivirus Glycoprotein Erns, a Long Tilted Amphipathic Helix.
2014. PLoS pathogens, 10 (2), Art. Nr.: e1003973. doi:10.1371/journal.ppat.1003973
Kügler, J. H.; Muhle-Goll, C.; Kühl, B.; Kraft, A.; Heinzler, R.; u. a.
Trehalose lipid biosurfactants produced by the actinomycetes Tsukamurella spumae and T. pseudospumae.
2014. Applied microbiology and biotechnology, 98 (21), 8905–8915. doi:10.1007/s00253-014-5972-4
Jehle, K.; Cato, L.; Neeb, A.; Muhle-Goll, C.; Jung, N.; u. a.
Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif.
2014. Journal of biological chemistry, 289 (13), 8839–8851. doi:10.1074/jbc.M113.534859
Luy, B.; Muhle-Goll, C.
Organische Chemie 2013. Magnetische Resonanz.
2014. Nachrichten aus der Chemie, 62, 282–283
Peschko, K.; Schade, A.; Vollrath, S. B. L.; Schwarz, U.; Muhle-Goll, C.; u. a.
Dendrimer-type peptoid-decorated hexaphenylxylenes and tetraphenylmethanes: Synthesis and structure in solution and in the gas phase.
2014. Chemistry - a European journal, 20, 16273–16278. doi:10.1002/chem.201404024
2013
Rist, M. J.; Muhle-Goll, C.; Görling, B.; Bub, A.; Heissler, S.; u. a.
Influence of Freezing and Storage Procedure on Human Urine Samples in NMR-Based Metabolomics.
2013. Metabolites, 3 (2), 243–258. doi:10.3390/metabo3020243
Kudryavtsev, K. V.; Ivantcova, P. M.; Churakov, A. V.; Wiedmann, S.; Muhle-Goll, C.; u. a.
Alternating asymmetric self-induction in functionalized pyrrolidine oligomers.
2013. Angewandte Chemie - International Edition, 52 (48), 12736–12740. doi:10.1002/anie.201302862
Beuerle, F.; Krueger, A.; Lehmann, M.; Bach, T.; Muhle-Goll, C.; u. a.
Organische Chemie 2012.
2013. Nachrichten aus der Chemie, 61 (3), 265–297. doi:10.1002/nadc.201390087
Luy, B.; Muhle-Goll, C.
Trendberichte Organische Chemie: Magnetische Resonanz.
2013. Nachrichten aus der Chemie, 61, 295
Sternberg, U.; Birtalan, E.; Jakovkin, I.; Luy, B.; Muhle-Goll, C.; u. a.
Structural Characterization of a Peptoid with Lysine-like Side Chains and Biological Activity using NMR and Computational Methods.
2013. Organic and Biomolecular Chemistry, 11 (4), 640–647. doi:10.1039/c2ob27039k
2012
Maddalo, D.; Neeb, A.; Jehle, K.; Schmitz, K.; Muhle-Goll, C.; u. a.
A Peptidic Unconjugated GRP78/BiP Ligand Modulates the Unfolded Protein Response and Induces Prostate Cancer Cell Death.
2012. PLoS one, 7 (10), Art.Nr. e45690. doi:10.1371/journal.pone.0045690
Windisch, D.; Hoffmann, S.; Afonin, S.; Vollmer, S.; Muhle-Goll, C.; u. a.
Structural investigation of the transmembrane segment of the PDGF receptor beta and the oncoprotein E5 by circular dichoroism and NMR.
2012. Biophysical Society 56th Annual Meeting, San Diego, Calif., February 25-29, 2012 Biophysical Journal, 102(2012) No.3 Suppl.1, a (Abstract)
Windisch, D.; Hoffmann, S.; Muhle-Goll, C.; Grage, S.; Bürck, J.; u. a.
Structural investigations of the heterotetrameric E5/PDGF-receptor β complex by oriented circular dichroism and solid state NMR.
2012. Biophysical Society 56th Annual Meeting, San Diego, Calif., February 25-29, 2012
Jakovkin, I.; Klipfel, M.; Muhle-Goll, C.; Ulrich, A. S.; Luy, B.; u. a.
Rapid calculation of protein chemical shifts using bond polarization theory and its application to protein structure refinement.
2012. Physical chemistry chemical physics, 14 (35), 12263–12276. doi:10.1039/c2cp41726j
Muhle-Goll, C.; Hoffmann, S.; Afonin, S.; Grage, S. L.; Polyanski, A. A.; u. a.
Hydrophobic matching controls the tilt and stability of the dimeric platelet-derived growth factor receptor (PDGFR) β transmembrane segment.
2012. The journal of biological chemistry, 287 (31), 26178–2686. doi:10.1074/jbc.M111.325555
Klein, M. J.; Grage, S. L.; Muhle-Goll, C.; Bürck, J.; Afonin, S.; u. a.
Structure analysis of the membrane-bound PhoD signal peptide of the Tat translocase shows an N-terminal amphiphilic helix.
2012. Biochimica et biophysica acta / Biomembranes, 1818 (12), 3025–3031. doi:10.1016/j.bbamem.2012.08.002
2011
Maddalo, D.; Neeb, A.; Jehle, K.; Schmitz, K.; Muhle-Goll, C.; u. a.
Bag-1 proteins inhibit prostate cancer cell growth through a distinct sequence that binds the glucose regulated protein GRP78.
2011. 3rd Internat.Meeting on Cell Stress and Apoptosis - to Arturo, Salerno, I, June 23-25, 2011
Maddalo, D.; Neeb, A.; Jehle, K.; Schmitz, K.; Muhle-Goll, C.; u. a.
Pro-apoptotic properties of Bag-1 peptides in the control of prostate cancer cell growth.
2011. 102nd Annual Meeting of the American Association for Cancer Research (AACR), Orlando, Fla., April 2-6, 2011 Cancer Research, 71(2011) Nr.8, Suppl.1 Abstract 5403
2010
Klein, M. J.; Bürck, J.; Muhle-Goll, C.; Walther, T. H.; Nolandt, O.; u. a.
Structure analysis of the prePhoD signal peptide: functional implications of an amphiphilic helix for approaching the Tat translocase.
2010. 24th Internat.Conf.on NMR in Biological Systems, Cairns, AUS, August 22-27, 2010
Grage, S. L.; Walther, T.; Muhle-Goll, C.; Jakovkin, I.; Sternberg, U.; u. a.
Structure of the pore-forming subunit of the twin arginine translocase determined by combining liquid- and solid-state NMR.
2010. 24th Internat.Conf.on NMR in Biological Systems, Cairns, AUS, August 22-27, 2010
Müller, L. N.; Muhle-Goll, C.; Biskup, M. B.
The Glc₂Man₂-fragment of the N-glycan precursor - a novel ligand for the glycan-binding protein malectin?.
2010. Organic and Biomolecular Chemistry, 8, 3294–99. doi:10.1039/C004502K
Windisch, D.; Hoffmann, S.; Afonin, S.; Vollmer, S.; Muhle-Goll, C.; u. a.
Structural role of the conserved cysteines in the dimerization of the viral transmembrane oncoprotein E5.
2010. Biophysical Journal, 99, 1764–72. doi:10.1016/j.bpj.2010.06.073
Hilpert, K.; McLeod, B.; Yu, J.; Elliott, M. R.; Muhle-Goll, C.; u. a.
Short cationic antimicrobial peptides interact with ATP.
2010. Antimicrobial Agents and Chemotherapy, 54, 4480–83. doi:10.1128/AAC.01664-09
Muhle-Goll, C.; Walther, T.; Grage, S.; Jakovkin, I.; Sternberg, U.; u. a.
Structure of the pore-forming subunit of the twin arginine translocase determined by combining liquid- and solid-state NMR.
2010. World Wide Magnetic Resonance 2010 : Joint EUROMAR 2010 and 17th ISMAR Conf., Firenze, I, July 4-9, 2010
Muhle-Goll, C.; Melchers, J.; Diechtierow, M.; Füller, F.; Ulrich, A. S.; u. a.
The strictly conserved Cys76 plays a crucial role in the conformational stability of reduced Px III.
2010. EMBO Conf.’Catalytic Mechanisms by Biological Systems : at the Interface Between Chemistry and Biology’, Hamburg, May 5-7, 2010
Schallus, T.; Feher, K.; Sternberg, U.; Rybin, V.; Muhle-Goll, C.
Analysis of the specific interactions between the lectin domain of malectin and diglucosides.
2010. Glycobiology, 20, 1010–20. doi:10.1093/glycob/cwq059
Windisch, D.; Hoffmann, S.; Muhle-Goll, C.; Bürck, J.; Afonin, S.; u. a.
Structural features of the transmembrane E5 oncoprotein from bovine papillomavirus.
2010. Biophysics of Membrane-Active Peptides : 455th WE-Heraeus-Seminar, Bad Honnef, April 11-14, 2010
Hoffmann, S.; Windisch, D.; Muhle-Goll, C.; Bürck, J.; Afonin, S.; u. a.
Structural characterization of the transmembrane helix of the platelet-derived growth factor receptor-β.
2010. Biophysics of Membrane-Active Peptides : 455th WE-Heraeus-Seminar, Bad Honnef, April 11-14, 2010
2009
Palma, A. S.; Liu, Y.; Campanero-Rhodes, M. A.; Childs, R. A.; Muhle-Goll, C.; u. a.
Malectin - a novel lecitin of the endoplasmic reticulum and a candidate new player in the early steps of protein N-glycosylation.
2009. Annual Meeting of the Society for Glycobiology, Fort Worth, Tex., November 12-15, 2008 Glycobiology, 18(2008) (Abstract)
Palma, A. S.; Liu, Y.; Campanero-Rhodes, M. A.; Childs, R. A.; Muhle-Goll, C.; u. a.
Malectin - a novel lecitin of the endoplasmic reticulum and a candidate new player in the early steps of protein N-glycosylation.
2009. Annual Meeting of the Society for Glycobiology, Fort Worth, Tex., November 12-15, 2008 Glycobiology,(2008) (Abstract), 18, 948
Klein, M. J.; Bürck, J.; Muhle-Goll, C.; Callow, P.; Walther, T. H.; u. a.
Interactions of the Tat-dependent signal peptide of B.subtilis with the Tat-translocase.
2009. CFN Summer School on Nano-Biology, Bad Herrenalb, September 8-11, 2009
Windisch, D.; Hoffmann, S.; Muhle-Goll, C.; Bürck, J.; Vollmer, S.; u. a.
Influence of the conserved cysteines on the membrane structure of the bovine papillomavirus E5 oncoprotein.
2009. Signal Transduction and Disease : Trinat.Fall Meeting 2009 of the Societies of Biochemistry and Molecular Biology of Belgium, Germany and the Netherlands, Aachen, September 27-30, 2009
Hoffmann, S.; Windisch, D.; Muhle-Goll, C.; Bürck, J.; Afonin, S.; u. a.
Role of the transmembrane helix of plateled-derived growth factor β receptor.
2009. Signal Transduction and Disease : Trinat.Fall Meeting 2009 of the Societies of Biochemistry and Molecular Biology of Belgium, Germany and the Netherlands, Aachen, September 27-30, 2009
Schallus, T.; Feher, K.; Ulrich, A. S.; Stier, G.; Muhle-Goll, C.
Structure and dynamics of the human muscle LIM protein.
2009. FEBS Letters, 583, 1017–22. doi:10.1016/j.febslet.2009.02.021
Schallus, T.; Feher, K.; Palma, A. S.; Liu, Y.; Muhle-Goll, C.; u. a.
Malectin - a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein N-glycosylation.
2009. 3rd EU-NMR Annual User Meeting, Autrans, F, January 26-29, 2009
2008
Walther, T. H.; Grage, S. L.; Muhle-Goll, C.; Bürck, J.; Müller, S. D.; u. a.
Structural characterization of the Tat-translocase pore forming protein TatAsub(d) from B. subtilis.
2008. 8th Internat.Conf.on Magnetic Resonance in Biological Systems, San Diego, Calif., August 24-29, 2008
Feher, K.; Groves, P.; Batta, G.; Jimenez-Barbero, J.; Muhle-Goll, C.; u. a.
Competition saturation transfer difference experiments improved with isotope editing and filtering schemes in NMR-based screening.
2008. Journal of the American Chemical Society, 130, 17148–153. doi:10.1021/ja804468k
Melchers, J.; Diechtierow, M.; Feher, K.; Sinning, I.; Muhle-Goll, C.; u. a.
Structural basis for a distinct catalytic mechanism in trypanosoma brucei tryparedoxin peroxidase.
2008. Journal of Biological Chemistry, 283, 30401–11. doi:10.1074/jbc.M803563200
Koenig, P.; Oreb, M.; Rippe, K.; Muhle-Goll, C.; Sinning, I.; u. a.
On the significance of Toc-GTPase homodimers.
2008. Journal of Biological Chemistry, 283, 23104–12. doi:10.1074/jbc.M710576200
Schallus, T.; Jaeckh, C.; Feher, K.; Palma, A. S.; Muhle-Goll, C.; u. a.
Malectin: A novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein n-glycosylation.
2008. Molecular Biology of the Cell, 19, 3404–14. doi:10.1091/mbc.E08-04-0354
Jakovkin, I.; Sternberg, U.; Muhle-Goll, C.; Witter, R.; Ulrich, A. S.
Non empirical computation of protein NMR properties - a rapid and accurate approach using bond polarization theory.
2008. 8th Triennial Congress of the World Association of Theoretical and Computational Chemists (WATOC 2008), Sydney, AUS, September 14-19, 2008
Muhle-Goll, C.
Study of the catalytic cycle of GPX3 from trypanosoma brucei.
2008. EU-NMR Annual User Meeting, Königstein, January 23-25, 2008