Science Highlights
Nanobio users from the John Sack group at UC Davis worked with Bruce Cohen to develop a new probe for imaging voltage sensors. Endogenous Voltage-sensor Activity Probe or EVAP was developed by using peptidyl tarantula toxin conjugated to fluorophore for two-photon imaging. This probe then allowed them to detect conformation changes in voltage sensors in rat brain slices. Their work was featured on the cover of the Journal of General Physiology.
Nanobio users Cassio Pedroso and Victor Mann working with Bruce Cohen and the Craik group at UCSF designed SpyCatcher conjugated Quantum Dots that can be covalently linked to any antibody. These modular materials can then be used to deliver fluorescent nanoparticles into cells for targeting and imaging of receptors. Their work appears in the journal ACS Nano.
During the pandemic as the lab shutdown for several months, Molecular Foundry staff collaborated with users from Stanford to develop antimicrobial peptoids to fight viruses like SARS-CoV-2. Their work appears in the journal pharmaceuticals and is highlighted by LBL and Stanford.
Molecular Foundry Users and staff developed SpyCatcher-based engineering of nanoparticle surfaces to synthesize photonic materials on crystalline two-dimensional protein sheets. Using orthogonal bioconjugation reactions, QDs, Au nanoparticles, and upconverting nanoparticles were patterned along the S-layer protein SbsB
Molecular Foundry Users and staff developed the first nanoparticles able to host photon avalanches, an extreme nonlinear optical behavior. These thulium-doped ANPs can be imaged at resolutions of under 70 nm without special microscopes or data processing, opening up a world of high-resolution bioimaging experiments.
2020
Corie Ralston and Sayan Gupta along with collaborators from UCSF used microsecond X-ray foot-printing at the ALS and Molecular Foundry to investigate Nanobody binding to SARS-CoV-2 Spike protein. Their work helped the effort to develop Nanobodies that can inactivated SARS-CoV-2. These materials can be used in aerosols to prevent to spread of viral infection. Their work appears in the most recent journal issue of Science.
Nanobio users Sebastian Fletcher-Taylor, Parashar Thapa, and Jon T. Sack working with Nanobio Staff Scientist Bruce Cohen developed a new fluorescent probe for voltage-gated potassium channels using tarantula toxin. The toxin is linked to a environment-sensative dye julolidine phenoxazone (JP) to interrogate the channel in live cells. Their work is published in ACS Chemical Neuroscience with the title "Distinguishing Potassium Channel Resting State Conformations in Live Cells with Environment-Sensitive Fluorescence."
For the past several months, the nanobio facility have been working to contribute to the national response to COVID-19, resulting in a range of materials for virus detection on protective equipment. Bruce Cohen, Victor Mann, Natalia Molcanova, and Zeming Wang, have been working to develop materails for these sensors. A recent LBL video highlights this work.
Nanobio user Christine Wang from the Center for Functional Materials at Brookhaven National Laboratories in work with Ron Zuckermann published their work on using peptoids to stabilize DNA origami structures. Using peptoids that were either “brush” or “block" polymers, they showed that DNA architectures can be stabilized for applications such as drug delivery to cells. Their work appears in the journal PNAS with the title "DNA origami protection and molecular interfacing through engineered sequence-defined peptoids."
Nanobio users Parsa Asachi, Uyen N.T. Nguyen, Jacqueline Dang, Ryan K. Spencer, and Hannah S. Martin with Ron Zuckermann published their work on making Skeletides. Skeletides are printable 3D models of proteins backbone that can be linked together to for the structures of proteins in solution. These models are able to self assemble in water, showcasing their ability to demonstrate the structure of proteins. Their work appears in the journal 3D Printing and Additive Manufacturing with the title "Skeletides: A Modular, Simplified Physical Model of Protein Secondary Structure."
2019
Spanning three institutions, and with work from four research groups including Ron Zuckermann and Gary Rend of the Molecular Foundry, researchers published their work on using sequence defined polymers as antibody mimics. Synthesizing a combinatorial library of thsese polymers known as peptoids, Kim et al assembled them into dimensional nanosheets and found several sequences that were able to target a protein antigen of anthrax. Their work appears in the journal ACS nano with the title "Discovery of Stable and Selective Antibody Mimetics from Combinatorial Libraries of Polyvalent, Loop-Functionalized Peptoid Nanosheets."
Nanobio staff members Michael Connolly and Ron Zuckermann along with collaborators from the University of Zurich and Novartis were able to design peptoids to isolate prion proteins from fluids sampled from infected animals. These peptoids could be used to screen for prions in human as well as animals. Their work appears in the journal PLOS one with the title "Enhanced detection of prion infectivity from blood by pre-analytical enrichment with peptoid-conjugated beads."
Nanobio users Andrew Wijaya, Andy Nguyen, Leah roe, and Ryan Spencer along with scientists from Theory Facility were able to control the conformation of peptoids. Using NMR, X-ray crystallography and DFT calculations, they were able to show control over the molecular structure by tuning the chemical structure of the peptoid monomers. Their work appears in the journal JACS with the title "Cooperative Intramolecular Hydrogne Bonding Strongly Enforces cis-Peptoid Folding."
Nanobio users Sunting Xuan and Xi Jiang along with the Theory Facility, Materials Science Division and UC Berkeley used cryo transmission electron microscopy and peptoid synthesis to investigate the response of peptoid nanosheet structure to chemical modifications at the atomic-length scale. Their work apperas in PNAS with the title "Atomic-level engineering and imaging of polypeptoid crystal lattices."
Nanobio users Nicole Torquato, Bining Tian, and Bruce Cohen in collaboration with the Anwar group at UCSF have integrated a custom integrated circuit imager design with nanoparticle engineering and introduced INSITE, a 25 micron-thin microscopic imaging platform. INSITE is a scalable, custom designed planar chip-based microscope, in combination with long-lifetime NIR upconverting nanoparticles. Using INSITE, they were able to image from an intratumorally-injected mouse prostate tumor specimen. Their work appers in the journal Theranostics with the title "A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination."
Nanobio users Daniel Murray, Jae Hong Kim and Elissa Grzincic along with scientists at UCSF were able to create peptoid bilayers and monolayers across large areas using deposition techniques. These peptoid films were then used for sensing pathogen derived proteins using interferometry. Their work appears in the journal Langmuir "Uniform, Large-Area, Highly Ordered Peptoid Monolayer and Bilayer Films for Sensing Applications."
A team of Foundry Users and Staff including Angel Fernandez-Bravo, Ed Barnard, Cheryl Tajon, Emory Chan and Jim Schuck along with researches at Northwestern University produced stable and continuous lasing at room temperature from plasmons smaller than the wavelength of light by combining user-designed nanopillar arrays with upconverting nanoparticles developed at the Foundry. These nanolasers exhibit the lowest ever lasing threshold compared to other plasmon or upconverting nanolasers, and offer stable, continuous-wave operation at room temperature. The work appears in Nature Materials with the title "Ultralow-threshold, continuous-wave upconverting lasing from subwavelength plasmons."
A team of Foundry Users and Staff including Bella Tian, Alexandra Courtis, and Bruce Cohen in the Nanobio Facility, detected cathodoluminescence emission spectra from individual sub-20-nm nanoparticles in 9 distinct colors. This work demonstrates functional cathodoluminescence in an electron microscope; The materials could enable new technology to study biological interaction in vivo and at high resolution. The work appears in Nature Nanotechnology with the title "Bright sub-20 nm cathodoluminescent nanoprobes for electron microscopy."
Nanobio user Ryan Spencer working with Ron Zuckermann, the Molecular Foundry Theory facility and reserachers from NYU published there study on peptoid chain confomation. Analysing 46 published petoid structures, Spencer et al find that the backbone dihedral angles fall into 4 primary conformers regardles of the constraints on the peptoid chain. The authors propose a classication and naming scheme for all peptoids to aid future research in the field. Their paper is titled "Stereochemistry of polypeptoid chain configurations" and appears in the latest issue of Biopolymers.
Nanobio users Leah Roe and Blakely Tresca working with Ron Zuckermann, the Molecular Foundry Theory facility and UC Berkeley published there work on using 2D-NMR to study peptoid structure. In this work, Roe et al determine the structure of 4 peptoid tetramers using 2D NMR and find that N‐(2‐aminoethyl)glycine residue stabilizes particular conformations. Their work lays the foundation for similar structural studies in other peptoid polymers. Their paper is titled "Unconstrained peptoid tetramer exhibits a predominant conformation in aqueous solution" and appears in the latest issue of Biopolymers.
Marimikel Charrier along with staff scientist Caroline Ajo-Franklin published their work on engineering Surface (S)-layer proteins on bacteria. These engineered S-Layers can be used to pattern and eventually assemble hybrid living materials. The other co-authors include Dong Li, Victor Mann, Lisa Yun, Sneha Jani, Behzad Rad, Bruce Cohen, Paul Ashby, and Kathleen Ryan. Their paper appears in ACS Synthetic Biology with the title "Engineering the S-Layer of Caulobacter crescentus as a Foundation for Stable, High-Density, 2D Living Materials"
Nanobio users Hee Jeung Oh an Whiney Loo from the Balsara group at UC Berkeley published their work on 3D printing polymer absorbers for cancer treatment. In an in vivo model, they show that a small polmer can be inserted into the blood stream to soak up a chemotherapeutic drug. Their paper appears in ACS Central Science with the title "3D Printed Absorber for Capturing Chemotherapy Drugs before They Spread through the Body"
2018
Congratulations to Rita Garcia on receiving the Directors Award for Exceptional Achievement for the founding chair of the Foundry Diversity, Equity, and Inclusion committee.
Nanobio users Andy Nguyen, Ryan Spencer along with Ron Zuckermann published their work on using peptoids to chelate multi-metal clusters. Using NMR and molecular models, they discover short peptoid oligomers that fold into a specific 3D conformation to bind Cobalt oxide. Their paper appears in Chemical Science with the title "A bio-inspired approach to ligand design: folding single-chain peptoids to chelate a multimetallic cluster."
Nanobio users Sam Light, Lin Su, and Jose Cornejo along with Caroline Ajo-Frankiln in collaboration with the Portnoy group at UC Berkeley published their work on electron transfer by a gram positive bacteria. Listeria monocytogenes was found to transfer electrons to extra-cellular materials using a previously unidentified cluster of eight genes. Their work appears in Nature with the title "A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria."
Nanobio users Raffaele Pugliese and Fabrizio Gelain along with Ron Zuckermann just published their work on cross-linked self assembling peptides. Using a genpin cross-linking reaction with a specific peptide sequence, they are able to make strong yet flexible nano-porous mats. These biomaterials may be used for tissue engineering. Their work appears in the journal Biomaterials Science with the title "Self-assembling peptides cross-linked with genipin: resilient hydrogels and self-standing electrospun scaffolds for tissue engineering applications"
Crystalline soft materials have been difficult to characterize at the atomic scale using electron microscopy. Nanobio user Doug Grier along with Ron Zuckermann, Ken Downings group from UC Berkeley and scientists at NCEM used tricks from cryoEM imaging to resolve peptoid polymer structures in single nanosheets. Their work appears in the journal Macromolecules with the title "Imaging Unstained Synthetic Polymer Crystals and Defects on Atomic Length Scales Using Cryogenic Electron Microscopy."
Nanobio user Bining Tian, Yue Tian, Cheryl Tajon, along with Bruce Cohen, and staff from the Imaging and Inorganic facility just published their work on alloyed upconverting nanoparticles (aUCNP). They show that these probes can be imaged at low laser power intensities and through deep tissue. Their work appears in an article with the title "Low irradiance multiphoton imaging with alloyed lanthanide nanocrystals" in Nature Communications.
The Molecular Foundry User Meeting is coming up on August 15 and 16. Submit an abstract by August 1 for the poster session or register here.
Nanobio user Cheryl Tajon, along with Bruce Cohen, NCEM, and the Inorganic facility just published their work on upconverting nanoparticles (UCNP) conjugated to fluorescent dyes. They show that these probes are 100-times more stable than free dyes, allowing them to be used for chemical sensing in living cells. Their work appears in an article with the title "Photostable and efficient upconverting nanocrystal-based chemical sensors" in Optical Materials.
Cheryl Tajon and Bruce Cohen working with the Inorganic and Imaging facility, published their work on developing nanoparticle microlasers. Using upconverting nanoparticles on microspheres, they developed a micron scale laser that is stable for several hours. Their work appears in an article with the title "Continuous-wave upconverting nanoparticle microlasers" in Nature Photonics.
Caroline Ajo-Franklin and Alison Hatt from the Molecular Foundry were honored at the Women @ The Lab awards ceremony. The award recognizes women "for their professional accomplishments, their contributions to STEM outreach, and their commitment and dedication to the Lab’s mission." Congratulations!
Jose Cornejo, Caroline Ajo-Franklin along with Heinz Frei's group in MBIB just published their work on nanoscale membranes. They use molecular wires embeded in a thin membrane to link electron transferring bacteria to electrodes, reducing ohmic losses and removing the incompatability between the living and non-living world. Their paper appears in Nature Communications with the title "Nanoscale membranes that chemically isolate and electronically wire up the abiotic/biotic interface."
Ryan Spencer and Ron Zuckermann working with the Steve Whitlam in the Theory Facility and researchers at the Georgia Institute of Technology published their work on peptoid conformations in nanosheets. Using molecular dynamics simulations, quantum theory and experimental data, they show that peptoid adopt a cis conformation, allowing peptoid chains to be linear and untwisted. This conformation also allows for dense packing as observed in the nanosheets. Their work was published in PNAS with the title "Conformations of peptoids in nanosheets result from the interplay of backbone energetics and intermolecular interactions."
Victor Mann, Alex Powers and Bruce Cohen along with Molecular Foundry Users published their work on developing Azide-Alkyne conjugation methods for quantum dots. Their work identified techniques to label the fluorescent nanocrystals with bio-molecules. Their work appears in ACS Nano in a paper titiled "Azide–Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination."
Nicole A. Torquato, Cheryl A. Tajon, Bining Tian, and Bruce Cohen from the nanobio facility, along with other Foundry users and staff recently published their work on enhancing UCNP with organic dye antennas. Their work appears in a Nature Photonics paper titled "Enrichment of molecular antenna triplets amplifies upconverting nanoparticle emission."
Alessia Battigelli, Ron Zuckermann along with collaborators from Georgia Institue of technology used 2D NMR to probe the conformation of peptoids in nanosheets. Their findings show that, surprisingly, the cis conformation is favored in the nanosheet. Their work was recently published in the Journal of Physical Chemistry Letters with the title "Evidence for cis Amide Bonds in Peptoid Nanosheets".
Alessia Battigelli, along with Ron Zuckermann and other Foundry staff and users recently published their work on sugar coated peptoid nanosheets. Mimicking the cell surface, these sheets pattern and present sugar groups on their surfaces, which selectively bind proteins. This platform could eventually be used to detect or inactivate pathogens. This work appears in ACS Nano in a paper titled "Glycosylated Peptoid Nanosheets as a Multivalent Scaffold for Protein Recognition".
Nanobio user Doug Greer working with researchers from the Nanobio and Theory facilities published his work on probing the structure of peptoid crystalline copolymers. Using X-ray scattering at the ALS and SLAC, they probed conformation of peptoid diblock polymers to find a preference for cis- rather than the expected trans- configuration. Their work appears in JACS and is available as an ASAP article.
Raffaelle Pugliese a nanobio user recently published his work in collaboration with Ron Zuckermann on cross-linked self-assembled peptides in the journal Nano Research. His work on creating stiffer peptide structures may aide in the formation of biomaterials for regenerative medicine.
2017
Ron Zuckermann along with collaborators at Stony Brook University published their work on foldamer dynamics. This computational work on these polymers sheds light on the transition of pre-biotic moleculs to living cells. Their work is published in PNAS in a paper titled "Foldamer hypothesis for the growth and sequence differentiation of prebiotic polymers"
Alyssa Zhou a nanobio user and Graduate student in the Maharbiz group, working with Moshe Baruch and Caroline Ajo-Franklin, recently published her work on "A portable bioelectronic sensing system (BESSY) for environmental deployment incorporating differential microbial sensing in miniaturized reactors" in PLOS One. They managed to miniaturize a bio-electronic sensing device to detect current from bacteria in liquid culture. The bio-hybrid device can be used to sense chemicals in the environment and may have applications in the detecting harmful toxins.
Researchers from the ALS, JEBI, and the Foundry led by Caroline Ajo-Franklin recently published work in the Journal of the American Chemical Society that details an unconventional coupling between a bacterial protein and a mineral. The paper "The Molecular Basis for Binding of an Electron Transfer Protein to a Metal Oxide Surface" used X-ray footprinting to elucidate the mechanism that allows the bacterium to breathe when oxygen is not available.
Sara Wichner a nanobio user and former graduate student in the Yildiz group recently published her work on synthesizing and conjugating CdSe/CdS quantum dots to kinesin and tracking the proteins motion at the nanometer scale. Her work was published in ACS Nano in a paper titled "Covalent Protein Labeling and Improved Single-Molecule Optical Properties of Aqueous CdSe/CdS Quantum Dots."
Th 10th peptoid summit was held August 10-11 at the Molecular Foundry. The meeting brought together 136 researcher from 8 countries and 20 US states to LBNL. Congratulations to all for hosting a successful event!
Foundry users from Molly Steven's group at the Imperial College London and the Nanobio and Imaging Facility recently published their work on amyloid fibrillation in the journal ACS Nano. In a paper titled "Sequence-Dependent Self-Assembly and Structural Diversity of Islet Amyloid Polypeptide-Derived β‑Sheet Fibrils" the authors studied the effects of peptide structure on amyloid self-assembly, which play a role in diseases such as Alzheimer’s and Huntington’s.
Foundry nanobio users from Steven Cobb's Research group measured the hydrophobicity, log D values, for a series of peptoids that mimic antimicrobial peptides. This work may aid in the design of more complicated peptoid-based polymers and structures. Their work is published in and featured on the cover of the July 7th issue of Peptide Science.
NASA astronaut Dr. Kathleen Rubins visited the Molecular Foundry on May 11. She toured the Nanobio facility, meeting with Caroline Ajo-Franklin, and then NCEM. Dr. Rubins then gave a talk on "Science in Extreme Environments: Building Extraterrestrial and Earth-Based Research Capabilities." Afterwards, she met with several scientists from the Foundry and JGI at a roundtable discussion. Her talk can be live streamed here (LDAP required).
Foundry users from the Segalman group at UCSB just reported their work on using polymers synthesized with peptides or peptoids for anti-fouling coatings. Their paper titled "Role of Backbone Chemistry and Monomer Sequence in Amphiphilic Oligopeptide- and Oligopeptoid-Functionalized PDMS- and PEO-Based Block Copolymers for Marine Antifouling and Fouling Release Coatings" was published in the journal Macromolecules.
Hannah Bolt, a member of Steven Cobb's Research group at Durham University in England and a nanobio user with Ron Zuckermann, published her work on using peptoids as antibacterial agents. Her work titled "Exploring the links between peptoid antibacterial activity and toxicity" appears in the journal Medicinal Chemical Communications.
The Molecular Foundry is hosting Part II of the Emotional Intelligence workshop on Wednesday January 11 from 12:30 to 2:00 pm in the Chemla room. Come by to learn how to be self aware of your emotions and how to effectively handle interpersonal relationships. No reservation is required. The work shop is hosted by the Foundry HR and the Career Development Committee.
2016
Jeffrey Kortright from the Materials Sciences Divison , Ron Zuckermann and users from the Biological Nanostructures facility just published their work on using soft x-rays on Beamline 6.3.2 at the ALS to probe a peptoid diblock system pNdcX-bpNteY. The paper titled "Oxygen K Edge Scattering from Bulk Comb Diblock Copolymer Reveals Extended, Ordered Backbones above Lamellar Order–Disorder Transition" was published in the Journal of Physical Chemistry B.
Ellen Robertson, Michael Nehls, and Ron Zuckermann just published the second part of their work on peptoid nanosheet formation. In an article featured on the cover and titled "Structure–Rheology Relationship in Nanosheet-Forming Peptoid Monolayers" they probe the chain–chain interactions in a variety of peptoid monolayers and showed that monolayer fluidity is an excellent predictor of the nanosheet-formation ability.
Nanobio user Ellen Robertson along with others in the Zuckermann group published their work in the journal Langmuir. Their study on engineering peptoid nanosheets is featured on the cover and appears in an article titled, "Molecular Engineering of the Peptoid Nanosheet Hydrophobic Core" . In addition, Caroline Proulx, Jessica K. Su, Rita L. Garcia, Stan Yoo, Eric M. Nehls, Michael D. Connolly, and Laudann Taravati contributed to the work. Congratulations!
Ron Zuckermann and his brother attended the opening of the new span of the bike path on the Bay Bridge named after their Father. Check out the video and news article featuring Ron here.
Nanobio user Chelsea Catania and Caroline Ajo-Franklin published a paper titled “Membrane Permeabilization by Conjugated Oligoelectrolytes Accelerated Whole-Cell Catalysis.” in the October 14 online issue of RSC Advances, ASAP (2016). Congratulations!
Ron Zuckermann gave an invited talk for the California Section of the American Chemical Society Regional Meeting, "New Soft-Matter Nanomaterials at the Intersection of Structural Biology and Polymer Science" on October 22 at Lawrence Berkeley Lab.
Cheryl Tajon and Bruce Cohen published their work on imaging UCNP in the September 7 issue of ACS Nano in a paper titled "Energy-Looping Nanoparticles: Harnessing Excited-State Absorption for Deep-Tissue Imaging." Yay!
Ron Zuckermann was invited to speak at the Foldemers conference in Bordeaux, France, which took place September 26-28. See the list of speakers and agenda here.
Caroline Ajo-Franklin and crew published their work on optimizing electron transfer in bacteria in in the March 22 issue of ACS Synthetic Biology in a paper titled CymA and exogenous flavins improve extracellular electron transfer and couple it to cell growth in Mtr-expressing Escherichia coli. Their work was featured on the cover! Congrats!