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Prof. Dr. Leonhard Möckl

  • Professorship for Nano-optical Imaging
  • Associated Group Leader
  • Room A.3.428
  • Phone +49 9131 7133115
  • Email
  • Head of research group Physical Glycosciences

Leonhard Möckl studied Chemistry and Biochemistry at LMU Munich. He obtained his PhD in 2015 with a thesis on the role of the glycocalyx in membrane protein organization. In 2016, he joined the lab of W.E. Moerner at Stanford University, where he used single-molecule techniques to investigate the glycocalyx and furthermore developed deep-learning based approaches for single-molecule studies. In 2020, he joined the MPL as an independent group leader. Since 2024, he holds the professorship for Nano-optical Imaging at FAU, located at the newly established CITABLE.

In his free time, he loves to read, to play the piano, to hike, and to play volleyball.

2019

Accurate phase retrieval of complex 3D point spread functions with deep residual neural networks

Leonhard Möckl, Petar N. Petrov, W. E. Moerner

APPLIED PHYSICS LETTERS 115 (25) 251106 (2019) | Journal

Phase retrieval, i.e., the reconstruction of phase information from intensity information, is a central problem in many optical systems. Imaging the emission from a point source such as a single molecule is one example. Here, we demonstrate that a deep residual neural net is able to quickly and accurately extract the hidden phase for general point spread functions (PSFs) formed by Zernike-type phase modulations. Five slices of the 3D PSF at different focal positions within a two micrometer range around the focus are sufficient to retrieve the first six orders of Zernike coefficients.

A Photoswitchable Trivalent Cluster Mannoside to Probe the Effects of Ligand Orientation in Bacterial Adhesion

Guillaume Despras, Leonhard Möckl, Anne Heitmann, Insa Stamer, Christoph Braeuchle, Thisbe K. Lindhorst

ChemBioChem 20 (18) 2373-2382 (2019) | Journal

We have recently demonstrated, by employing azobenzene glycosides, that bacterial adhesion to surfaces can be switched through reversible reorientation of the carbohydrate ligands. To investigate this phenomenon further, we have turned here to more complex-that is, multivalent-azobenzene glycoclusters. We report on the synthesis of a photosensitive trivalent cluster mannoside conjugated to an azobenzene hinge at the focal point. Molecular dynamics studies suggested that this cluster mannoside, despite the conformational flexibility of the azobenzene-glycocluster linkage, offers the potential for reversibly changing the glycocluster's orientation on a surface. Next, the photoswitchable glycocluster was attached to human cells, and adhesion assays with type 1 fimbriated Escherichia coli bacteria were performed. They showed marked differences in bacterial adhesion, dependent on the light-induced reorientation of the glycocluster moiety. These results further underline the importance of orientational effects in carbohydrate recognition and likewise the value of photoswitchable glycoconjugates for their study.

Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx

Leonhard Möckl, Kayvon Pedram, Anish R. Roy, Venkatesh Krishnan, Anna-Karin Gustavsson, Oliver Dorigo, Carolyn R. Bertozzi, W. E. Moerner

Developmental Cell 50 (1) 57-+ (2019) | Journal

The mammalian glycocalyx is a heavily glycosylated extramembrane compartment found on nearly every cell. Despite its relevance in both health and disease, studies of the glycocalyx remain hampered by a paucity of methods to spatially classify its components. We combine metabolic labeling, bioorthogonal chemistry, and super-resolution localization microscopy to image two constituents of cell-surface glycans, N-acetylgalactosamine (GalNAc) and sialic acid, with 10-20 nm precision in 2D and 3D. This approach enables two measurements: glycocalyx height and the distribution of individual sugars distal from the membrane. These measurements show that the glycocalyx exhibits nanoscale organization on both cell lines and primary human tumor cells. Additionally, we observe enhanced glycocalyx height in response to epithelial-to-mesenchymal transition and to oncogenic KRAS activation. In the latter case, we trace increased height to an effector gene, GALNT7. These data highlight the power of advanced imaging methods to provide molecular and functional insights into glycocalyx biology.

Physical Principles of Membrane Shape Regulation by the Glycocalyx

Carolyn R. Shurer, Joe Chin-Hun Kuo, LaDeidra Monet Roberts, Jay G. Gandhi, Marshall J. Colville, Thais A. Enoki, Hao Pan, Jin Su, Jade M. Noble, et al.

Cell 177 (7) 1757-+ (2019) | Journal

Cells bend their plasma membranes into highly curved forms to interact with the local environment, but how shape generation is regulated is not fully resolved. Here, we report a synergy between shape-generating processes in the cell interior and the external organization and composition of the cell-surface glycocalyx.Mucin biopolymers and long-chein polysaccharides within the glycocalyx can generates entropic forces that favor or disfavor the projection of spherical and finger-like extensions from the cell surface. A polymer brush model of the glycocalyx successfully predicts the effects of polymer size and cell-surface density on membrane morphologies. Specific glycocalyx compositions can also induce plasma membrane instabilities to generate more exotic undulating and pearled membrane structures and drive secretion of extracellular vesicles. Together, our results suggest a fundamental role the glycocalyx in regulating curved membrane features that serve in communication between cells and with the extracellular matrix.

Bisacylphosphane oxides as photo-latent cytotoxic agents and potential photo-latent anticancer drugs

Andreas Beil, Friederike A. Steudel, Christoph Braeuchle, Hansjorg Grutzmacher, Leonhard Möckl

Scientific Reports 9 6003 (2019) | Journal | PDF

Bisacylphosphane oxides (BAPOs) are established as photoinitiators for industrial applications. Light irradiation leads to their photolysis, producing radicals. Radical species induce oxidative stress in cells and may cause cell death. Hence, BAPOs may be suitable as photolatent cytotoxic agents, but such applications have not been investigated yet. Herein, we describe for the first time a potential use of BAPOs as drugs for photolatent therapy. We show that treatment of the breast cancer cell lines MCF-7 and MDA-MB-231 and of breast epithelial cells MCF-10A with BAPOs and UV irradiation induces apoptosis. Cells just subjected to BAPOs or UV irradiation alone are not affected. The induction of apoptosis depend on the BAPO and the irradiation dose. We proved that radicals are the active species since cells are rescued by an antioxidant. Finally, an optimized BAPO-derivative was designed which enters the cells more efficiently and thus leads to stronger effects at lower doses.

Zur logischen Position der Hypothese

Leonhard Möckl

Vernunft und Leben aus transzendentaler Perspektive. Festschrift für Albert Mues zum 80. Geburtstag. 145-154 (2019)

The concept of the hypothesis is omnipresent across all discipline of science, be it natural sciences or humanities. Despite the prominent role in everyday scientific work, its true meaning and logical position are remarkably elusive. In this essay, I argue that within the concept of the hypothesis, a twofold collision of categories occurs. First, the hypothesis needs to be connected to current, already achieved knowledge. At the same time, it may not be directly deduced from this knowledge: Therefore, its formulation has a necessary non-rational aspect. Second, in this dichotomic state, the hypothesis is in the moment of its formulation immediately revoked because the hypothesis is not meant to be permanent. Either, its connection to present knowledge survives if the hypothesis is later shown to be true. Or, its non-rational aspect survives if the hypothesis is disproven. Both these cases are thought as potential outcomes when the hypothesis is formulated. Hence, in this formulation, rationality and non-rationality collide twofold. The collision of these two categories cannot be resolved within the position of the categories rationality and non-rationality. If either of the two colliding categories are emphasised, paradoxes arise, for example in the question of responsibility for scientific research (ethics of conviction vs. ethics of responsibility). The hypothesis must, therefore, be traced back to its radically individual origin: The researcher who formulated it – nature itself does not know any hypothesis.

Here you can download Leonhard's CV.

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