California NanoSystems Institute
CNSI
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March 18, 2014

J. Andrew MacKay, Ph.D.
Assistant Professor, Pharmacology and Pharmaceutical Sciences, University of Southern California
Switchable Protein Polymers for Medicine and Biology

Abstract:

Biology is unparalleled at generating multifunctional materials at the nanoscale. Be they enzymes, antibodies, viral capsids or organelles, no technologies yet invented mimic their functionality and small size. Based on this observation, we harness recombinant engineering of protein polymers to assemble structures with applications in disease, biosensors, and the manipulation of the cell. Protein polymers are repetitive amino acid sequences, which can be: i) expressed in cells; ii) fused to functional peptides; III) tuned to respond to environmental cues, and iv) designed to biodegrade in biological microenvironments. We specialize in protein polymers that self-assemble into targeted nanoparticles. As they are composed entirely from genetically engineered materials, their composition can be precisely tailored at the DNA level. In recent years, we have designed systems with applications in cancer, ocular disease, and as tools to control intracellular trafficking pathways. An emerging technology, protein polymers facilitate the engineering of biological nanomaterials with a precision similar to that used to biosynthesize functional materials found in nature.

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March 04, 2014

Linda Baum, M.D., Ph.D.
Medical Director, UCLA Clinical Laboratories; Professor and Vice-Chair of Pathology and Laboratory Medicine at DGSOM
The UCLA Clinical Laboratories: What We Do and How We Can Help

Abstract:

The UCLA Clinical Laboratories is under the direction of 24 faculty members at UCLA, with expertise in Clinical Chemistry, Transfusion Medicine, Hematology and Coagulation, Clinical Microbiology, Molecular Pathology and Cytogenetics. The lab is one of the largest university-based clinical labs in the United States, performing approximately 6,000,000 lab tests/yr.

Linda Baum, M.D. Ph.D., Medical Director of the UCLA Clinical Laboratories, will lead an informal discussion to describe the expertise of the Clinical Laboratories and the faculty, and outline areas where the expertise of the Clinical Labs faculty may be helpful for investigators developing new types of diagnostic testing. There will be a brief presentation, and the remainder of the hour will be available to discuss individual projects and answer questions.

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February 19, 2014

Dr. Sung Park, Ph.D.
Molecular Vista, CEO
Park Scientific Instruments, Co-Founder
Seeing Molecules in Color

Abstract:

A few recent advances in scanning probe microscopy points to a potential tool that would allow researchers to study dynamics and structure of molecules with unprecedented spatial resolution. Molecular Vista has developed a tool called Molecular Resonance Force Microscope (RFM) on a high-speed AFM platform; the tool is built on a custom inverted optical setup, which is compatible with many far-field and near-field configurations. In addition to being able to collect near-field photons scattered by the AFM tip, RFM can also measure optical resonances such as electronic, plasmon and stimulated Raman scattering via force detection so that high resolution topography and chemical information are acquired concurrently in air and in liquid environments.

Data from the tool will be presented along with the description of the new tool.

February 11, 2014

Jörg Enderlein, Ph.D.
Department of Physics, Georg August University
Image Scanning Microscopy and Metal Induced Energy Transfer: Enhancing Microscopy Resolution in All Directions

Abstract:

Classical fluorescence microscopy is limited in resolution by the wavelength of light (diffraction limit) restricting lateral resolution to ca. 200 nm, and axial resolution to ca. 500 nm (at typical excitation and emission wavelengths around 500 nm). However, recent years have seen a tremendous development in high- and super-resolution techniques of fluorescence microscopy, pushing spatial resolution to its diffraction-dictated limits and much beyond. One of these techniques is Structured Illumination Microscopy (SIM). In SIM, the sample is illuminated with a spatially modulated excitation intensity distribution, and the emerging fluorescence is imaged with a conventional wide-field imaging setup. By moving and rotating the excitation intensity distribution pattern in different positions and orientations, taking each time a wide-field image, a final fluorescence image is composed which has roughly double the resolution (laterally) of a conventional wide-field or a confocal laser scanning image alone. A similar technique is Image Scanning Microscopy (ISM). In ISM, the focus of a conventional laser-scanning confocal microscope (LCSM) is scanned over the sample, but instead of recording only the total fluorescence intensity for each scan position, as done in conventional operation of an LCSM, one records a small image of the illuminated region. The result is a four-dimensional stack of data: two dimensions refer to the lateral scan position, and two dimensions to the pixel position on the chip of the image-recording camera. This set of data can then be used to obtain a super-resolved image with doubled resolution, completely analogously to what is achieved with SIM. However, ISM is conceptually and technically much simpler, suffers less from sample imperfections like refractive index variations, and can easily be implemented into any existing LSCM.

A second, completely different approach which aims at achieving nanometer resolution along the optical axis is Metal Induced Energy Transfer or MIET. When placing a fluorescent molecule close to a metal, its fluorescence properties change dramatically. In particular, one observes a strongly modified lifetime of its excited state (Purcell effect). This is due to the efficient electromagnetic coupling of the excited state to surface plasmons in the metal, which is similar to Förster Resonance Energy Transfer (FRET), where the energy of an excited donor molecule is transferred into the excited state of an acceptor molecule. We call this effect metal-induced energy transfer or MIET. The MIET-coupling between an excited emitter and a metal film is strongly dependent on the emitter’s distance from the metal. We have used this effect for mapping the basal membrane of live cells with an axial accuracy of ~3 nm. The method is easy to implement and does not require any change to a conventional fluorescence lifetime microscope; it can be applied to any biological system of interest, and is compatible with most other super-resolution microscopy techniques which enhance the lateral resolution of imaging. Moreover, it is even applicable to localizing individual molecules, thus offering the prospect of using single-molecule localization microscopy for structural studies of biomolecules and biomolecular complexes.

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