A5038302116- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- Nanopore and Nanochannel Transport Studies
- Monoclonal and Polyclonal Antibodies Research
- Advanced Fluorescence Microscopy Techniques
- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- Microfluidic and Bio-sensing Technologies
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Biomedical and Engineering Education
- Plasmonic and Surface Plasmon Research
- Teaching and Learning Programming
- Peptidase Inhibition and Analysis
- Supramolecular Self-Assembly in Materials
- Molecular Communication and Nanonetworks
- Genetics, Bioinformatics, and Biomedical Research
- Biochemical and Structural Characterization
- Electrostatics and Colloid Interactions
- Origins and Evolution of Life
- Spectroscopy and Quantum Chemical Studies
- Lipid metabolism and biosynthesis
- Advanced Electron Microscopy Techniques and Applications
University of Washington
2019-2025
University of Bonn
2022-2025
Ludwig-Maximilians-Universität München
2017-2025
Max Planck Institute of Biochemistry
2013-2023
Max Planck Institute of Psychiatry
2023
Lawrence Berkeley National Laboratory
2023
University of Lisbon
2012-2020
Max Planck Society
2013-2017
Quantitative BioSciences
2017
Membrane sculpting and transformation is essential for many cellular functions, thus being largely regulated by self-assembling self-organizing protein coats. Their functionality often encoded particular spatial structures. Prominent examples are BAR domain proteins, the 'banana-like' shapes of which thought to aid scaffolding membrane tubulation. To elucidate whether 3D structure can be uncoupled from other functional features complex we hereby develop curved DNA origami in various stacking...
Abstract The healthy growth and maintenance of a biological system depends on the precise spatial organization molecules within cell through dissipation energy. Reaction–diffusion mechanisms can facilitate this organization, as directional cargo transport orchestrated by motor proteins, relying specific protein interactions. However, material also be achieved active processes based non-specific, purely physical mechanisms, phenomenon that remains poorly explored. Here, using combined...
Computationally designed multi-subunit assemblies have shown considerable promise for a variety of applications, including new generation potent vaccines. One the major routes to such materials is rigid body sequence-independent docking cyclic oligomers into architectures with point group or lattice symmetries. Current methods and designing are tailored specific classes symmetry difficult modify novel applications. Here we describe RPXDock, fast, flexible, modular software package rigid-body...
Programming protein nanomaterials to respond changes in environmental conditions is a current challenge for design and important targeted delivery of biologics. Here we describe the octahedral non-porous nanoparticles with targeting antibody on two-fold symmetry axis, designed trimer programmed disassemble below tunable pH transition point three-fold tetramer four-fold axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components,...
Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. Although computational methods for designing novel self-assembling proteins advanced substantially over the past decade, they primarily focus on static structures. Here we characterize three distinct computationally designed exhibit unanticipated structural diversity arising from flexibility in their subunits. Cryo-EM single-particle reconstructions and native mass...
The cell membrane is a heterogeneously organized composite with lipid-protein micro-domains. contractile actin cortex may govern the lateral organization of these domains in membrane, yet underlying mechanisms are not known. We recently reconstituted minimal cortices (MACs) (Vogel et al., 2013b) and here advanced our assay to investigate effects rearranging filaments on by introducing various phase-separated lipid mono- bilayers MACs. addition reorganized domains. found that process reached...
Abstract Widespread control of gene expression through translation has emerged as a key level spatiotemporal regulation protein expression. A prominent mechanism by which ribosomes can confer is via internal ribosomal entry sites (IRESes), whose functions have however, remained difficult to rigorously characterize. Here we present set technologies in embryos and cells, including IRES-mediated circular RNA (circRNA) reporters, single-molecule messenger (m)RNA isoform imaging, PacBio long-read...
DNA origami nanotechnology is being increasingly used to mimic membrane-associated biophysical phenomena. Although a variety of nanostructures has already been produced target lipid membranes, the requirements for membrane binding have so far not systematically assessed. Here, we set elongated structures with varying placement and number cholesteryl-based anchors compare different strategies their incorporation. Single multiple cholesteryl were attached using single- double-stranded spacers...
DNA nanostructures offer the possibility to mimic functional biological membrane components due their nanometer-precise shape configurability and versatile biochemical functionality. Here we show that diffusional behavior of assembly into higher order membrane-bound lattices can be controlled in a stop-and-go manner process monitored with super-resolution imaging. The structures are transiently immobilized on glass-supported lipid bilayers by changing mono- divalent cation concentrations...
DNA origami is a state-of-the-art technology that enables the fabrication of nano-objects with defined shapes, to which functional moieties, such as lipophilic anchors, can be attached nanometre scale precision. Although binding lipid membranes has been extensively demonstrated, specific requirements necessary for membrane attachment are greatly overlooked. Here, we designed set amphipathic rectangular-shaped structures varying placement and number chol-TEG anchors used attachment. Single-...
Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that hydrophobic interfaces drive nanoparticle assembly are predicted to form cryptic transmembrane domains, suggesting interaction with membrane insertion machinery could limit efficient secretion. We develop general...
Single-particle plasmon spectroscopy has become a standard technique to detect and quantify the presence of unlabeled macromolecules. Here, we extend this method determine their exact distance from sensors with sub-nanometer resolution by systematically varying sensing range into surrounding adjusting size plasmonic nanoparticles. We improved current single-particle record continuously for hours scattering spectra thousands nanoparticles different sizes simultaneously 1.8 s time resolution....
Here, biophysical properties of membranes enriched in three metabolically related sterols are analyzed both vitro and vivo. Unlike cholesterol ergosterol, the common metabolic precursor zymosterol is unable to induce formation a liquid ordered (lo) phase model lipid can easily accommodate gel phase. As result, has marginal ability modulate passive membrane permeability vesicles with different compositions, contrary ergosterol. Using fluorescence-lifetime imaging microscopy (FLIM) an...
Recent research regarding 2-hydroxylated fatty acids (2OHFAs) showed clear evidence of their benefits in the treatment cancer, inflammation, and neurodegenerative disorders such as Alzheimer's disease. Monolayer compressibility isotherms isothermal titration calorimetry 2OHFA (C18-C22) phosphatidylcholine/phosphatidylethanolamine/sphingomyelin/cholesterol (1:1:1:1 mole ratio), a mixture that mimics composition mammalian plasma membrane, were performed to assess membrane binding capacity...
Abstract Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. For example, clathrin coats adopt a wide variety of architectures adapt vesicular cargos various sizes. Although computational methods for designing novel self-assembling proteins advanced substantially over the past decade, most existing focus on static with high accuracy. Here we characterize three distinct computationally designed each form multiple unanticipated...
Abstract Organization of elongated particles into ordered phases on 2D surfaces and interfaces has been extensively studied during the last decades both theoretically experimentally. For mutually repulsive solid nondeformable substrates, process is controlled only by aspect ratio surface density adsorbed particles. The local elastic response soft substrates to particle adhesion can drastically change collective behavior rod‐like resulting in their self‐organization via substrate‐mediated...
Abstract Computationally designed multi-subunit assemblies have shown considerable promise for a variety of applications, including new generation potent vaccines. One the major routes to such materials is rigid body sequence-independent docking cyclic oligomers into architectures with point group or lattice symmetries. Current methods and designing are tailored specific classes symmetry difficult modify novel applications. Here we describe RPXDock, fast, flexible, modular software package...
Abstract Programming protein nanomaterials to respond changes in environmental conditions is a current challenge for design and important targeted delivery of biologics. We describe the octahedral non-porous nanoparticles with three symmetry axes (four-fold, three-fold, two-fold) occupied by distinct homooligomers: de novo designed tetramer, an antibody interest, trimer programmed disassemble below tunable pH transition point. The assemble cooperatively from independently purified...
In bottom-up synthetic biology, one of the major methodological challenges is to provide reaction spaces that mimic biological systems with regard topology and surface functionality. Of particular interest are cell- or organelle-shaped membrane compartments, as many protein functions unfold at lipid interfaces. However, shaping artificial cell using materials non-intrusive physicochemical properties, while maintaining flexible interfaces relevant reconstituted systems, not straightforward....
Abstract Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion from eukaryotic cells would be advantageous, but in practice they often secrete poorly. Here we show that hydrophobic interfaces drive nanoparticle assembly are predicted to form cryptic transmembrane domains, suggesting interaction with membrane insertion machinery could limit efficient secretion. We develop...
Undergraduate research experiences can improve student success in graduate education and STEM careers. During the COVID-19 pandemic, undergraduate researchers at our institution many others lost their work–study positions due to interruption of in-person activities. This imposed a financial burden on students eliminated an important learning opportunity. To address these challenges, we created paid, fully remote, cohort-based curriculum computational protein design. Our used existing design...