Honors & Awards
Presentation at the Symposium on the Science of Light, MPI Erlangen (2019)
Best poster prize ChEM-H retreat, ChEM-H, Stanford University (2017)
PhD Prize of the LMU Munich, Munich University Society (2016)
Römer Prize for PhD thesis, Römer Foundation (2016)
Römer Prize for master's thesis, Römer Foundation (2014)
CeNS Publication Award, Center for Nanoscience Munich (2012)
Scholarship, German Academic Scholarship Foundation (2009)
Doctor of Philosophy, Ludwig Maximilian Universitat Munchen (2015)
Master of Science, Ludwig Maximilian Universitat Munchen (2013)
Bachelor of Science, Ludwig Maximilian Universitat Munchen (2011)
Abitur, Kaiser Heinrich High School Bamberg (2008)
William Moerner, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
Superresolution Microscopy, Glycobiology, Metabolic Labeling
William Moerner, (11/1/2016)
Supersensitive Multifluorophore RNA-FISH for Early Virus Detection and Flow-FISH by Using Click Chemistry
The reliable detection of transcription events through the quantification of the corresponding mRNA is of paramount importance for the diagnostics of infections and diseases. The quantification and localization analysis of the transcripts of a particular gene allows disease states to be characterized more directly compared to an analysis on the transcriptome wide level. This is particularly needed for the early detection of virus infections as now required for emergent viral diseases, e. g. Covid-19. In situ mRNA analysis, however, is a formidable challenge and currently performed with sets of single-fluorophore-containing oligonucleotide probes that hybridize to the mRNA in question. Often a large number of probe strands (>30) are required to get a reliable signal. The more oligonucleotide probes are used, however, the higher the potential off-target binding effects that create background noise. Here, we used click chemistry and alkyne-modified DNA oligonucleotides to prepare multiple-fluorophore-containing probes. We found that these multiple-dye probes allow reliable detection and direct visualization of mRNA with only a very small number (5-10) of probe strands. The new method enabled the in situ detection of viral transcripts as early as 4 hours after infection.
View details for DOI 10.1002/cbic.202000081
View details for Web of Science ID 000527258700001
View details for PubMedID 32187837
Deep learning in single-molecule microscopy: fundamentals, caveats, and recent developments [Invited].
Biomedical optics express
2020; 11 (3): 1633–61
Deep learning-based data analysis methods have gained considerable attention in all fields of science over the last decade. In recent years, this trend has reached the single-molecule community. In this review, we will survey significant contributions of the application of deep learning in single-molecule imaging experiments. Additionally, we will describe the historical events that led to the development of modern deep learning methods, summarize the fundamental concepts of deep learning, and highlight the importance of proper data composition for accurate, unbiased results.
View details for DOI 10.1364/BOE.386361
View details for PubMedID 32206433
The Emerging Role of the Mammalian Glycocalyx in Functional Membrane Organization and Immune System Regulation
Frontiers in Cell and Developmental Biology
View details for DOI 10.3389/fcell.2020.00253
- Accurate phase retrieval of complex 3D point spread functions with deep residual neural networks APPLIED PHYSICS LETTERS 2019; 115 (25)
- Physical Principles of Membrane Shape Regulation by the Glycocalyx CELL 2019; 177 (7): 1757-+
Bisacylphosphane oxides as photo-latent cytotoxic agents and potential photo-latent anticancer drugs
2019; 9: 6003
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.
View details for DOI 10.1038/s41598-019-42026-y
View details for Web of Science ID 000464342700028
View details for PubMedID 30979960
View details for PubMedCentralID PMC6461680
Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx.
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.
View details for DOI 10.1016/j.devcel.2019.04.035
View details for PubMedID 31105009
A Photoswitchable Trivalent Cluster Mannoside to Probe the Effects of Ligand Orientation in Bacterial Adhesion.
Chembiochem : a European journal of chemical biology
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.
View details for DOI 10.1002/cbic.201900269
View details for PubMedID 31026102
Accurate and rapid background estimation in single-molecule localization microscopy using the deep neural network BGnet.
Proceedings of the National Academy of Sciences of the United States of America
Background fluorescence, especially when it exhibits undesired spatial features, is a primary factor for reduced image quality in optical microscopy. Structured background is particularly detrimental when analyzing single-molecule images for 3-dimensional localization microscopy or single-molecule tracking. Here, we introduce BGnet, a deep neural network with a U-net-type architecture, as a general method to rapidly estimate the background underlying the image of a point source with excellent accuracy, even when point-spread function (PSF) engineering is in use to create complex PSF shapes. We trained BGnet to extract the background from images of various PSFs and show that the identification is accurate for a wide range of different interfering background structures constructed from many spatial frequencies. Furthermore, we demonstrate that the obtained background-corrected PSF images, for both simulated and experimental data, lead to a substantial improvement in localization precision. Finally, we verify that structured background estimation with BGnet results in higher quality of superresolution reconstructions of biological structures.
View details for DOI 10.1073/pnas.1916219117
View details for PubMedID 31871202
- Invasiveness of Cells Leads to Changes in Their Interaction Behavior with the Glycocalyx ADVANCED BIOSYSTEMS 2018; 2 (8)
The Endothelial Glycocalyx Controls Interactions of Quantum Dots with the Endothelium and Their Translocation across the Blood–Tissue Border
2017; 11 (2): 1498
View details for DOI 10.1021/acsnano.6b06812
- Azido pentoses: A New Tool to Efficiently Label Mycobacterium tuberculosis Clinical Isolates ChemBioChem 2017
New insights into the intracellular distribution pattern of cationic amphiphilic drugs
View details for DOI 10.1038/srep44277
More Than 50 Years after Its Discovery in SiO2 Octahedral Coordination Has Also Been Established in SiS2 at High Pressure
2017; 56 (1): 372-377
View details for DOI 10.1021/acs.inorgchem.6b02294
Dendrimer-based signal amplification of click-labelled DNA in situ
View details for DOI 10.1002/cbic.201700209
The glycocalyx regulates the uptake of nanoparticles by human endothelial cells in vitro
2017; 12 (3): 207-217
View details for DOI 10.2217/nnm-2016-0332
En route from artificial to natural: Evaluation of inhibitors of mannose-specific adhesion of E. coli under flow.
Biochimica et biophysica acta
2016; 1860 (9): 2031-2036
We investigated the properties of six Escherichia coli adhesion inhibitors under static and under flow conditions. On mannan-covered model substrates and under static conditions, all inhibitors were able to almost completely abolish lectin-mediated E. coli adhesion. On a monolayer of living human microvascular endothelial cells (HMEC-1), the inhibitors reduced adhesion under static conditions as well, but a large fraction of bacteria still managed to adhere even at highest inhibitor concentrations. In contrast, under flow conditions E. coli did not exhibit any adhesion to HMEC-1 not even at inhibitor concentrations where significant adhesion was detected under static conditions. This indicates that the presence of shear stress strongly affects inhibitor properties and must be taken into account when evaluating the potency of bacterial adhesion inhibitors.
View details for DOI 10.1016/j.bbagen.2016.06.021
View details for PubMedID 27345501
- Artificial Formation and Tuning of Glycoprotein Networks on Live Cell Membranes: A Single-Molecule Tracking Study CHEMPHYSCHEM 2016; 17 (6): 829-835
100 Jahre Einkristallzucht aus der Schmelze - Vom Spreeknie ins Silicon Valley
CHEMIE IN UNSERER ZEIT
2016; 50 (6)
View details for DOI 10.1002/ciuz.201600759
Switching first contact: photocontrol of E. coli adhesion to human cells
2016; 52 (6): 1254-1257
We have shown previously that carbohydrate-specific bacterial adhesion to a non-physiological surface can be photocontrolled by reversible E/Z isomerisation using azobenzene-functionalised sugars. Here, this approach is applied to the surface of human cells. We show not only that bacterial adhesion to the azobenzene glycoside-modified cell surface is higher in the E than in the Z state, but add data about the specific modulation of the effect.
View details for DOI 10.1039/c5cc08884d
View details for Web of Science ID 000368353600037
View details for PubMedID 26612767
Microdomain Formation Controls Spatiotemporal Dynamics of Cell-Surface Glycoproteins
2015; 16 (14): 2023-2028
The effect of galectin-mediated microdomain formation on the spatiotemporal dynamics of glycosylated membrane proteins in human microvascular endothelial cells (HMEC-1) was studied qualitatively and quantitatively by high-resolution fluorescence microscopy and artificially mimicked by metabolic glycoprotein engineering. Two types of membrane proteins, sialic acid-bearing proteins (SABPs) and mucin-type proteins (MTPs), were investigated. For visualization they were metabolically labeled with azido sugars and then coupled to a cyclooctyne-conjugated fluorescent dye by click chemistry. Both spatial (diffusion) and temporal (residence time) dynamics of SABPs and MTPs on the membrane were investigated after treatment with exogenous galectin-1 or -3. Strong effects of galectin-mediated lattice formation were observed for MTPs (decreased spatial mobility), but not for SABPs. Lattice formation also strongly decreased the turnover of MTPs (increased residence time on the cell membrane). The effects of galectin-mediated crosslinking was accurately mimicked by streptavidin-mediated crosslinking of biotin-tagged glycoproteins and verified by single-molecule tracking. This technique allows the induction of crosslinking of membrane proteins under precisely controlled conditions, thereby influencing membrane residence time and the spatial dynamics of glycans on the cell membrane in a controlled way.
View details for DOI 10.1002/cbic.201500361
View details for Web of Science ID 000362815900009
View details for PubMedID 26296625
- With logical Sharpness and systematic Inflexibility Wichard von Moellendorff CHEMIE IN UNSERER ZEIT 2015; 49 (4): 236-247
Two High-Pressure Phases of SiS2 as Missing Links between the Extremes of Only Edge-Sharing and Only Corner-Sharing Tetrahedra
2015; 54 (4): 1240-1253
The ambient pressure phase of silicon disulfide (NP-SiS2), published in 1935, is orthorhombic and contains chains of distorted, edge-sharing SiS4 tetrahedra. The first high pressure phase, HP3-SiS2, published in 1965 and quenchable to ambient conditions, is tetragonal and contains distorted corner-sharing SiS4 tetrahedra. Here, we report on the crystal structures of two monoclinic phases, HP1-SiS2 and HP2-SiS2, which can be considered as missing links between the orthorhombic and the tetragonal phase. Both monoclinic phases contain edge- as well as corner-sharing SiS4 tetrahedra. With increasing pressure, the volume contraction (-ΔV/V) and the density, compared to the orthorhombic NP-phase, increase from only edge-sharing tetrahedra to only corner-sharing tetrahedra. The lattice and the positional parameters of NP-SiS2, HP1-SiS2, HP2-SiS2, and HP3-SiS2 were derived in good agreement with the experimental data from group-subgroup relationships with the CaF2 structure as aristotype. In addition, the Raman spectra of SiS2 show that the most intense bands of the new phases HP1-SiS2 and HP2-SiS2 (408 and 404 cm(-1), respectively) lie between those of NP-SiS2 (434 cm(-1)) and HP3-SiS2 (324 cm(-1)). Density functional theory (DFT) calculations confirm these observations.
View details for DOI 10.1021/ic501825r
View details for Web of Science ID 000349656600015
View details for PubMedID 25590815
Cell-Penetrating and Neurotargeting Dendritic siRNA Nanostructures
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2015; 54 (6): 1946-1949
We report the development of dendritic siRNA nanostructures that are able to penetrate even difficult to transfect cells such as neurons with the help of a special receptor ligand. The nanoparticles elicit strong siRNA responses, despite the dendritic structure. An siRNA dendrimer directed against the crucial rabies virus (RABV) nucleoprotein (N protein) and phosphoprotein (P protein) allowed the suppression of the virus titer in neurons below the detection limit. The cell-penetrating siRNA dendrimers, which were assembled using click chemistry, open up new avenues toward finding novel molecules able to cure this deadly disease.
View details for DOI 10.1002/anie.201409803
View details for Web of Science ID 000349209200052
View details for PubMedID 25522332
Super-resolved Fluorescence Microscopy: Nobel Prize in Chemistry 2014 for Eric Betzig, Stefan Hell, and William E. Moerner
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
2014; 53 (51): 13972-13977
A big honor for small objects: The Nobel Prize in Chemistry 2014 was jointly awarded to Eric Betzig, Stefan Hell, and William E. Moerner "for the development of super-resolved fluorescence microscopy". This Highlight describes how the field of super-resolution microscopy developed from the first detection of a single molecule in 1989 to the sophisticated techniques of today.
View details for DOI 10.1002/anie.201410265
View details for Web of Science ID 000346484400001
View details for PubMedID 25371081
- Optical Investigations to clear up a Mystery The Wittelsbach and the Hope Diamond CHEMIE IN UNSERER ZEIT 2012; 46 (6): 356-364
Tuning Nanoparticle Uptake: Live-Cell Imaging Reveals Two Distinct Endocytosis Mechanisms Mediated by Natural and Artificial EGFR Targeting Ligand
2012; 12 (7): 3417-3423
Therapeutic nanoparticles can be directed to cancer cells by incorporating selective targeting ligands. Here, we investigate the epidermal growth factor receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide. Highly sensitive live-cell fluorescence microcopy with single particle resolution unraveled the existence of two different uptake mechanisms; EGF triggers accelerated nanoparticle endocytosis due to its dual active role in receptor binding and signaling activation. For GE11, an alternative EGFR signaling independent, actin-driven pathway is presented.
View details for DOI 10.1021/nl300395q
View details for Web of Science ID 000306296200011
View details for PubMedID 22632479