Seminars & Events

Fall 2014 update: While the cross-divisional organizing committee has been dissolved, the initiative's vision continues to be advanced by ad-hoc cross-divisional teams.

The LBNL Integrated Bioimaging Seminars have been discontinued; we hope to start a new bioimaging series in the future.

LBNL Integrated Bioimaging Seminars (monthly)

Seminars are scheduled the first Wednesday of each month from 4:00 to 5:00 p.m.. Each one hour seminar includes two 20 min. presentations and discussion time. For questions and speaker suggestions, or to be included in the bioimaging seminars email list, please contact

Seminars are held at 717 Potter Street, Berkeley, CA 94710: s
how your LBNL badge and sign in at the security desk upon arrival; obtain a parking pass at this desk or contact 24 hrs in advance.)

(Summer break)

June 4, 2014
717 Potter St., room 141

Seema Singh, Joint BioEnergy Institute and Sandia National Laboratories
"Light, Force and (Inter)Action: Advanced Imaging Technologies for Biofuels Research"

Biofuels produced from lignocellulosic biomass and microalgae feedstock have tremendous potential to reduce U.S. dependence on imported petroleum derived fuels and chemicals, and ensure environmental security. Yet even architectural details of lignocellulosic plant and understanding of oil production in microalgae have eluded scientist for decades. This talk will present several advanced technologies for studying biomass The talk will demonstrate how light and force and its interactions with biomass are advancing our fundamental understanding or biomass properties and enabling biofuels research.

May 7, 2014
717 Potter St., room 141
Focused on Radiochemical Imaging - from Microbes to Humans

Nick Vandehey, Life Sciences Division (O'Neil Lab)
"4-D, Longitudinal Radioisotope Imaging of Microbial Systems at the Bench-top Scale"

Microbial communities residing from the earth’s surface down to the bedrock play critical roles in both Carbon Cycling and Environmental Remediation. Using techniques adapted from medical imaging research, we are studying the role of microbes in soils and sediments, aiming to characterize their function and location with specific interest in the spatial heterogeneity of microbes within a microcosm. The penetrating nature of gamma rays makes radioisotope imaging methods ideally suited for this application and scale of imaging as other imaging techniques often applied to such systems have a more limited field of view or are destructive to the sample. This talk will discuss results of experiments related to imaging biomass and biogeochemistry in saturated sediment and measuring the spatial distribution of CO2 uptake by cyanobacteria in biological surface crusts.


Suzanne Baker, Life Sciences Division (Jagust Lab)
"Brain Imaging to Detect Early Signs of Dementia"

Amyloid is a protein that can accumulate in the brain and is a precursor to Alzheimer's Disease.  Methodological considerations in detecting early amyloid deposition in older adults will be discussed, as well as optimizing information from such positron emission tomography (PET) scans.

April 2
, 2014
717 Potter St., room 141

Focused on
tools and techniques for imaging living cells
(host: Damir Sudar)

Mustafa A. H. Mir, UC Berkeley (Sohn Lab)

"Quantitative Phase Imaging for Characterizing Living Biological Systems"

Measuring cellular level phenomena is challenging because of the transparent nature of cells and tissues, the multiple temporal and spatial scales involved, and the need for both high sensitivity and throughput. Quantitative phase imaging (QPI) is an emerging field that addresses this need by providing highly sensitive information on cellular growth, motility, dynamics, and spatial organization in a completely label-free manner. These parameters can be measured from the sub-micron to millimeter scales and timescales ranging from milliseconds to days. In this talk I will discuss the principles of QPI and illustrate its advantages through examples of both clinical and basic science applications.


Bruce Cohen, The Molecular Foundry, Biological Nanostructures Laboratory

"Non-Luminescent Nanocrystals that Make Exceptional Single-Molecule Imaging Probes"

Imaging cells at the single-molecule level reveals spatial and temporal heterogeneity that is lost in ensemble imaging experiments. An ongoing challenge is the development of probes with the photostability, brightness, and continuous emission necessary at higher single-molecule excitation powers. Lanthanide-doped upconverting nanoparticles (UCNPs) overcome problems of photostability and continuous emission, can be imaged without background autofluorescence, and their upconverted emission can be  excited with biologically benign NIR light at much lower powers than those required for conventional multiphoton imaging probes. But the brightness of UCNPs has been limited by a poor understanding energy transfer and relaxation within individual nanocrystals and unavoidable trade-offs between brightness and size.  We have developed protein-sized UCNPs  that are over an order of magnitude brighter under single-particle imaging conditions than the brightest ensemble compositions, allowing us to visualize single upconverting nanoparticles as small as GFP.  We use a combination of advanced characterization (single-nanocrystal lifetimes and full emission spectra) and advanced theoretical modeling to find that surface effects become critical at d < 20 nm, and that the higher laser intensities used in single-molecule imaging fundamentally change the factors that determine nanocrystal brightness. We find that factors known to increase brightness in bulk experiments are unimportant at higher excitation intensities, and that, paradoxically, the brightest probes under single-molecule excitation are not luminescent at the ensemble level.

March 5, 2014
717 Potter St., room 141

Focused on
Soil Biogeochemical Imaging (host: Peter Nico)

Eoin Brodie, Earth Sciences Division, Berkeley Lab
"Mapping Soil Heterogeneity at the Microbial Scale"

Soils regulate the geochemical flux of most life-critical elements, control the production of food and renewable energy products, purify water for the biosphere, and regulate atmospheric greenhouse gases. Recently, it has become apparent that the processes governing soil C cycling occur, and vary, on fine spatial scales (nm-µm) and it is increasingly clear that observations made at these scales may be critical to predicting change at larger (m-km) scales. An understanding of these fine-scale interactions requires co-coordinated research across many disciplines. The goal of this LDRD is to develop a predictive understanding of how physical, chemical, and biological components interact to govern soil biogeochemistry, with a specific focus on microbial processes relevant to climate change. We are integrating approaches in imaging (radioisotope, 3D EM and synchrotron), microbiology (metagenomics and genome-based modeling) and mass spectroscopy to identify, quantify, and ultimately model activity hotspots in soil from the meter to nanometer scale. This presentation will discuss some of our recent highlights in technology development and integration.


Jennifer Pett-Ridge, Lawrence Livermore National Laboratory
“Small-Talk: Imaging Microbe-Mineral Interactions and Microbe-Microbe Elemental Trafficking”

A picture is worth a thousand words. Early developments in light microscopy revolutionized our understanding of the physical relationships microorganisms build with their surroundings. Now, newly-developed imaging methods allow insight into the chemical relationships microorganisms build. By combining techniques such as imaging mass spectrometry (NanoSIMS), SEM/TEM, and synchrotron-based approaches (e.g. STXM/NEXAFS and SRXTM), microbe-microbe, microbe-mineral, and microbe-organic matter associations and interactions can be characterized at a scale and specificity not before achieved. I will describe examples where these imaging approaches have been used (along with stable isotope tracing) to measure elemental trafficking in complex microbial systems (hypersaline microbial mats); link microbial identify and geochemical function (marine carbon cycling), and trace the flow and fate of organic molecules in soil.

February 5, 2014

717 Potter St., room 141
Focused on Image Analysis challenges in Integrated Bioimaging (Host: Ben Bowen)

Oliver Ruebel, Visualization Group, Computational Research Division, Berkeley Lab
"Mass Spectrometry Imaging in the World of Modern Data Sciences"

Mass spectrometry imaging (MSI) is widely applied to image complex samples for applications spanning health, microbial ecology, and high throughput screening of high-density arrays. MSI has emerged as a technique suited to resolving metabolism within complex cellular systems; where understanding the spatial variation of metabolism is vital for making a transformative impact on science. Unfortunately, the scale of MSI data and complexity of analysis presents an insurmountable barrier to scientists where a single 2D-image is many gigabytes and comparison of multiple images is beyond the capabilities available to most scientists. In this presentation we will identify and discuss common data challenges in modern imaging and demonstrate how we are addressing these challenges in the context of mass spectrometry imaging as part of the OpenMSI project and web-based gateway for management and storage of MSI data ( In particular, we will discuss the role of modern data formats, data provenance, and modern RESTful data interfaces as enablers for modern data-driven imaging experiments.


Peter Nugent, Computational Research Division, Berkeley Lab
"Making Effective Use of Machine Learning in Astrophysical Imaging Surveys"

Astrophysics is transforming from a data-starved to a data-swamped discipline, fundamentally changing the nature of scientific inquiry and discovery.  The observational data obtained during this decade alone will supersede everything accumulated over the preceding four thousand years of astronomy. Currently there are 4 large-scale imaging and spectroscopic surveys underway, each generating and/or utilizing tens of terabytes of data per year. Some will focus on the static universe while others will greatly expand our knowledge of transient phenomena. Maximizing the science from these programs requires integrating the processing pipeline with high-performance computing resources coupled
to large astrophysics databases while making use of machine learning algorithms with near real-time turnaround. Here I will present an overview of one of these programs, the Palomar Transient Factory (PTF). I will cover the processing and discovery pipeline we developed at LBNL and NERSC for it and several of the great discoveries made during the 4 years of observations with PTF.

Past Seminars 2013

November 6
, 2013
Note location: Bldg. 15, room 253

Dan Fletcher, Physical Biosciences Division "The Rise of Mobile Phone Microscopes"

Modern optical microscopes provide a unique window into the inner workings of biological systems, with new techniques offering improvements in resolution, sensitivity, and speed.  However, as microscopes gain capabilities, they often become more expensive, more difficult to use, and less available.  Not every experiment requires the latest microscopy technology, and many studies simply need greater availability of basic microscopy capabilities coupled with advanced image processing.  In a side project that grew out of an undergraduate optics class, my lab has been developing low-cost mobile microscopes that take advantage of the high sensitivity cameras now available in mobile phones.  This talk will describe recent efforts to build microscopes to image infectious bacteria, parasitic worms, and viral infections.  Our work is pointing to the potential for low-cost mobile microscopes to expand access to high-quality imaging both inside and outside the traditional laboratory setting.


Paul Adams, Physical Biosciences Division "New Algorithms for Obtaining High Quality Atomic Structures from Crystallographic and Cryo-EM Data"

X-ray crystallography is a well established technique that is now routinely used to determine the structures of macromolecules. It is able to provide atomic resolution information that has been a prerequisite to the understanding the fundamentals of life, from the structure of the double helix to the structures of intact ribosomes. It is also a method that is central to the development of new therapeutics for human disease. Increasingly, researchers are studying larger complexes and/or systems will inherent flexibility, often leading to low resolution diffraction data. This lack of experimental observations presents challenges for obtaining high quality atomic models. We have developed new computational methods for improving models even in the presence of low resolution crystallographic data. Single particle cryo-electron microscopy is a technique that has been applied to the study of large molecular complexes. With the advent of new electron detectors this method is developing rapidly and is now approaching atomic resolution, making is feasible to build and refine atomic models. The latter is hampered by a lack of computational algorithms tailored to cryo-EM data. We have developed new methods that make it possible to optimize molecular models with respect to prior chemical knowledge and the experimentally derived density maps.

October 2, 2013
Location: 717 Potter St., room 141

Luis Comolli, Ph.D., Life Sciences Division, "Correlating Genomics and Function Through 3-D Cryo-TEM of Intact Environmental Microbial Cells"

Although cryogenic transmission electron microscopy (cryo-TEM) has been available for many years, it has rarely been applied to environmentally-relevant organisms. This in part due to the difficulty in preparing cryogenic TEM samples from microorganisms that cannot be cultured.   Cryo-TEM has already changed our view of microbial cell architecture, and cryogenic electron tomography (cryo-ET) is becoming a more widely used technique worldwide. Consequently, there is a potential interest in using this technology as an approach to study environmental microbial systems. These systems are challenging because they are often remote, not possible to culture, difficult to transport artifact-free and intact, and "dirty" of minerals and nanoparticles although such particles contribute to their interest. Here we demonstrate that these obstacles can be overcome. Our results include unprecedented cryo-TEM and cryo-ET image data on intact cells and small pieces of biofilm from environmental sites for which genomics and proteomics data are available. This first successful application of cryo-TEM to microorganisms within the in-situ context of their mutual interactions and extracellular minerals opens the way to similar studies in many other relevant model and environmental systems in microbial ecology and geomicrobiology.


David Knowles, Ph.D., Life Sciences Division, "Creating Digital Atlases of Embryogenesis"

Creating embryonic digital atlases has become an emerging multidisciplinary field. The goal is to quantitatively capture the dynamic 3D arrays of multiple cell types, which animals comprise, into a digital record from which biological processes can be studied. I will discuss how we are using high resolution optical imaging and developing new computational techniques in computer vision to analyze the complex morphology of late-stage embryos, with their 40,000 cells, 70 cell types and all major organs. I will present some of the biological finding. This work extends our VirtualEmbryo (, a digital morphology and gene expression atlas of the early-stage, Blastoderm, Drosophila embryo.

September 4, 2013  Seminar Recording
Location: 717 Potter St., room 141

Ke Xu, Ph.D., Department of Chemistry, University of California-Berkeley, "A Novel, Periodic Cytoskeleton in Neurons Revealed by Sub-10 nm Super-Resolution Fluorescence Microscopy"

Actin filaments (microfilaments) constitute a major cytoskeleton in eukaryotic cells and play key roles in numerous cellular processes. However, it has been a great challenge to visualize actin and related cytoskeleton structures in cells owing to their small dimensions and high packing density. Our recent work has substantially advanced super-resolution fluorescence microscopy and achieved sub-10 nm optical resolution for biological samples. The improved resolution enabled us to optically resolve actin filaments in mammalian cells for the first time. In particular, in neurons we discovered a novel cytoskeleton structure that is highly ordered at the nanometer-scale. We found that actin filaments are arranged into ring-like structures in axons, and the rings are evenly spaced along the axon with a well-defined 190 nm spacing, resulting in a ladder-like, periodic lattice with long-range order. We further pinpointed the molecular mechanism underlying this novel structure: spectrin tetramers connect adjacent actin rings, thus regulating the periodicity of the lattice and forming a cohesive cytoskeleton. This novel, periodic cytoskeleton is only found in axons, and besides providing mechanical support for the membrane, it further arranges sodium ion channels, the signal generators of neurons, into similar periodic patterns along the axon.


Joaquin Correa, NERSC, "Integrated Tools for NGBI--Lessons Learned and Successful Cases"

NextGen Bioimaging (NGBI) requires a reliable and flexible solution for multi-modal, high-throughput and high-performance image processing and analysis. In order to solve this challenge, we have developed an OMERO-based modular and flexible platform that integrates a suite of general-purpose processing software, a set of custom-tailored algorithms, specific bio-imaging applications and NERSC's high performance computing resources and its science gateways.
This under-development platform provides a shared scalable one-stop-shop web-service for producers and consumers of models built on imaging data to refine pixel data into actionable knowledge resources.

June 5, 2013
Location: 717 Potter St., room 141

Shahid Khan, Molecular Biology Consortium at LBNL, "Remodeling of the Dendritic Spine Cytoskeleton by Synaptic Stimulation"

Synaptic stimulation results in a sub-minute increase in spine size. The rapidity of the response implies it is governed by cytoskeletal dynamics. The calcium calmodulin dependent kinase II (CaMKII) has a central role. CaMKII has actin as well as myosin motors as its binding targets. The binding is regulated by intracellular calcium transients triggered by stimulation. We are taking a three pronged approach based on live cell imaging, in vitro assays and computer modelling to investigate actomyosin organization and its regulation by CaMKII. I will present photo-activation and single molecule fluorescence data from cell cultures that develop mechanistic models.  I will also report on a minimal in-vitro system that we are developing to understand the physical rules underlying actomyosin self-organization and its regulation by CaMKII.


Manfred Auer, Life Sciences Division, "Branching Morphogenesis and Breast Cancer: Multiscale Multimodal Imaging of the Mammary Gland"

Development, function and disease of the mammary gland needs to be understood at the level of individual proteins and their contribution to the overall function, but also at the level of cell organelles, entire cells and tissues in order to understand changes in function and morphology underlying physiology and disease. Using a combination of time lapse video phase contrast and fluorescence microscopy, biomarker immunohistochemistry, wide-field high resolution transmission electron microscopy as well as the novel large volume 3D imaging approaches (Focused Ion Beam SEM and Serial Block Face SEM), we were able to determine the cellular strategies for branching morphogenesis resulting in an expanding and migrating yet functional tissue. In particular we will focus on the change in cell and tissue polarity and the presence of  extensive membrane network (invadipodia). We will demonstrate the many similarities between the developing tissue and mammary epithelial S1 cell acini and T4 aggregates grown in 3D matrix culture, with a focus on the mechanotransducive intermediate filament network and its interaction with the nuclear membrane. Our collaborative research on the mammary gland is the poster child for why integrated bioimaging matters and how combining multiple imaging modalities is the key for our understanding of complex biological processes such as the biology and pathology of tissues.

May 1
, 2013
Note location: Building 84, room 318

Carolyn Larabell, UCSF and Physical Biosciences Division
    "Correlated Fluorescence and X-ray Tomography of Nuclear Organization and Chromatin Topology"
With soft X-ray Tomography (SXT), we obtain images of cell structures with a spatial resolution of 50nm or better. Cells are imaged using photons in the water window, where organic material absorbs approximately an order of magnitude more strongly than water, generating a quantifiable high-contrast image of cellular structures. We used SXT to characterize the nuclear organization of unfixed, unstained cells at different development stages, from stem cells to post-mitotic mature cells. We also used SXT to elucidate the organization of olfactory receptor genes in olfactory neurons and to shed light on a 20 year old mystery surrounding the monogenic and monoalllelic expression of these genes (Clowney et al., 2012. Cell, 151, 724-737). To obtain molecular information, we designed a cryogenic light microscope for correlated fluorescence and X-ray tomography and revealed the structural organization of the inactive X chromosome in the native state.

Paul Ashby, Material Sciences Division
    "New Probes and Algorithms for Imaging Proteins and Cells with High Speed and Resolution Using Atomic Force Microscopy"
Atomic Force Microscopy regularly images materials with nanometer resolution. When imaging cells and proteins in solution the resolution is compromised when the soft sample deforms. I will present new AFM probes that are 10 times more gentle for higher resolution. I will also present our recent developments enabling high speed imaging and our fabrication of the fastest AFM.

April 3, 2013
Note location: Building 84, room 318

Erwin Frise, Life Sciences Division---[NEW--Dan Fletcher's talk has been postponed]
"Fiji: A Complete Open Image Processing Environment for the Biosciences"
    Fiji is a very popular distribution of ImageJ that includes modules for image acquisition, processing of optical microscopy images and electron microscopy images, and extraction of quantitative features from image data. It gives bioscientists a user friendly Photoshop like software and computational researchers a large library and feature rich platform for developing and distributing their algorithms. This talk will show how Fiji succeeds in being an open platform useful for many aspects of bioimage research and introduce new developments, including the new, even more powerful, ImageJ2.

Robert Glaeser, Life Sciences Division
"In-focus Phase Contrast for Cryo-EM"
    Cryo-EM images of protein complexes are currently recorded with a large defocus in order to generate partial phase contrast. Several groups are now developing alternative technologies, however, which might allow one to record in-focus images with nearly full phase contrast. We, for example, are developing a novel variant of the “Foucault knife edge” aperture, suitable for use in electron microscopy. To illustrate its high level of performance, in-focus cryo-EM images have been recorded in which individual ~55 kDa streptavidin tetramers are clearly visible by eye. Monolayer crystals of streptavidin have also been used to show that the image resolution extends to better than 4 Å. It thus is shown that the potential exists to expand the use of cryo-EM to encompass much more of the proteome than at present. The current focus of this project is to increase the useable (i.e. charging-free) lifetime of these apertures to weeks or even months, rather than the current limitation of several hours or days.

March 6, 2013

Ben Bowen, Life Sciences Division
"OpenMSI: Making Mass Spectrometry Imaging Accessible"
    The OpenMSI platform is an advanced data management, analysis and visualization resources for mass spectrometry imaging accessible
to scientists via the web. Mass spectrometry imaging (MSI) is widely applied to image complex samples for applications spanning health, microbial ecology, and energy sciences. MSI has emerged as a technique suited to resolving metabolism within complex cellular systems; where understanding the spatial variation of metabolism is vital for making a transformative impact on science.  Unfortunately, the scale of MSI data and complexity of analysis presents an insurmountable barrier to scientists where a single 2D-image may be 60GB and comparison of multiple images is beyond the capabilities available to most scientists. To overcome this, the OpenMSI project facilitates broad use of MSI by providing a web-based gateway for management and storage of MSI data, the visualization of the hyper-dimensional contents of the data, and the statistical analysis of the data. As a result, OpenMSI will make mass spectrometry imaging accessible as a standard method in imaging laboratories.

Puey Ounjai, Life Sciences Division (Ken Downing lab)
"Architectural Insights into Ciliary Partition"
    Ciliary compartmentalization plays pivotal roles in ciliogenesis and in various signaling pathways. Combining single particle analysis and electron cryo-tomography, we have identified and characterized a structure at the ciliary base that appears to have all the features required for compartmentalization and which we thus call the "ciliary partitioning system" (CPS). This complex consists of the terminal plate, which serves as a cytosolic "ciliary pore complex" (CPC), and a membrane region well suited to serve as a diffusion barrier. The CPC is a plate-shaped structure containing nine pores through which the microtubule doublets of the basal body pass. Each pore expands from the doublet B-tubule into an opening well suited for the passage of intraflagellar transport particles. The membrane diffusion barrier encompasses an extended region of detergent-resistant periciliary membrane (ciliary pocket) and a ring complex that connects the CPC to the membrane. Proteomics analysis shows involvement of the ciliary pocket in vesicle trafficking, suggesting that this region plays an active role in membrane transport. The CPC and the ring together form a complete partition defining the ciliary boundary.

February 6, 2013

Abby Dernburg, Life Sciences Division and UC Berkeley
"Challenges in Imaging of Living, Moving Targets"
    Work in my lab focuses on chromosome dynamics during meiosis. We are increasingly using in vivo imaging to better understand this process. I will discuss both the benefits of this approach, and the challenges that it creates.

Dula Parkinson, Advanced Light Source
3D Micron-scale Bioimaging at the Advanced Light Source
    CAT (Computed Axial Tomography) Scanners are familiar in medical settings as a tool to provide slices through 3D objects, without requiring the physical slicing of the object. The extraordinary brightness of the x-rays at the Advanced Light Source makes it possible to perform real-time tomography at high resolution. The non-invasive nature of this instrument has allowed us to obtain high resolution internal images of samples such as fossils and minute spider musculature. The high speed of the instrument has allowed imaging of dynamic biological processes including water transport in plants, root-soil interactions, and changes in plant tissue during pretreatment for biofuel production. A major new effort is underway to streamline and automate the transfer and processing of the large amount of data produced by this technique, making it much easier for new users of the instrument to quickly visualize and extract information from collected images.

Past Seminars 2012

December 5, 2012

Vikram Bajaj, Materials Sciences Division

"Extending the Limits of Sensitivity and Resolution in NMR and MRI"
    Magnetic resonance techniques peer into materials and objects in their unaltered native states and elucidate the structure, chemistry, and dynamics within. This motivates many applications of NMR and MRI in the laboratory, the clinic, and in industry alike. Nevertheless, several possible applications of NMR are limited by its low sensitivity, due to the weak equilibrium polarization of nuclear Zeeman states on which the signal intensity depends. This, in turn, limits the spatial resolution of conventional MRI experiments. I will discuss several techniques we are developing to overcome these limitations. These include dynamic nuclear polarization, a technique for electron-nuclear spin polarization transfer that has dramatically broadened NMR applications in solid materials; remote detection, by which NMR can be combined with microfluidic "lab on a chip" devices to produce novel analytical instruments; and, finally, optically detected NMR techniques that combine the sensitivity of optical spectroscopy with the chemical fidelity of magnetic resonance in micro- to nano-scale imaging experiments.

Sylvain Costes, Life Sciences Division
"High-throughput Cell Tracking Reveals DNA Repair Centers in Human Cells"
    By expressing DNA damage sensor proteins such as 53BP1 tagged with GFP, one can study the response of live human epithelial cells exposed to ionizing radiation. 53BP1 gets recruited to sites of DNA damage within a few minutes following exposure to radiation, leading to the formation of bright foci in the nucleus.  A microfluidics platform allowing precise control of cellular ambient conditions and automatic cell feeding is installed on a fully automated fluorescent microscopy platform. An open-source high-throughput application allows sophisticated cell tracking and ancestry recording. The response of hundreds of individual cells to radiation is measured as a function of cell cycle and the long-term fate of cell progeny can be fully characterized. The usage of sophisticated imaging and image processing have confirmed the existence of preferential sites of DNA repair in the nucleus and bring new insight regarding the impact of chromatin structure on radiation sensitivity.

November 7, 2012

Giovanni Birarda, Earth Sciences Division (Hoi-Ying Holman lab)
"Synchrotron Infrared Imaging for Biological Sciences"

Berkeley Synchrotron Infrared Structural Biology (BSISB) Program

    Biological systems are complex and dynamic, sensitive at times to even the slightest change in temperature or presence of a chemical stressor. As a result, a prominent challenge that has been presented to the research community is how one may characterize these systems without perturbing them. Infrared microspectroscopy (IRMS) offers a label-free and non-destructive alternative to many of the currently available techniques, this minimizing the damage and unintentional changes to the system at a molecular level while providing a wealth of chemical information about the target system. The use of Synchrotron radiation (SR) in parallel with detector modifications and advancements at LBNL’s Advanced Light Source (ALS) enables users to obtain both chemical and spatial information on their analytes of interest at the diffraction limit of the IRMS technique. In this presentation, we will broadly discuss the applications of IRMS and imaging to the life sciences, explaining the analytical capabilities of the technique through the presentation of projects to which this technique has successfully been applied. From following biochemical processes inside single cells to a study of cellular compositional changes resulting from commonly practiced fixation processes, I hope elucidate the potential of IRMS imaging as an applicable technique in biology while describing a subset of BSISB’songoing projects that range from imaging improvement to the incorporation of complementary technologies.

Musahid Ahmed, ALS / Chemical Dynamics Beamline
Imaging Mass Spectrometry with Lasers, Ion Beams, and Synchrotrons"
    Chemical imaging methods provide simultaneously information of a sample’s chemical composition and spatial heterogeneity.  In this program, imaging mass spectrometry is being performed with ion sputtering and laser desorption in conjunction with tunable vacuum ultraviolet (VUV) radiation generated at the Advanced Light Source. Knowledge gained from studies of fundamental desorption and ionization mechanisms are being applied to imaging lignin and plant biomass, following molecular transformations in soil organic matter, establishing microbial decomposition of plant biomass, and establishing the chemical composition and structure of biological material (i.e. melanin and lignin). I will discuss recent progress in elucidating the chemical structure of melanin – a material that has potential for novel optical and electronic applications. I will also briefly describe our new efforts in correlated optical imaging with ambient pressure mass spectrometry.

October 3, 2012

Peter Nico, Earth Sciences Division
"Imaging Microbe, Organic Matter, Mineral Interactions via Coupled STXM and NanoSIMS Analysis"
    Advancing understanding of soil organic-mineral interactions requires disentangling the complex interactions between soil mineral surfaces, decomposed organic compounds, and soil microbes in structurally intact soil. To avoid method-related artifacts that are associated with the common physical soil fractionation techniques, non-invasive high-resolution imaging techniques have been recently developed to simultaneously determine the molecular composition, source and fate of added OM, and location of OM within soil micro-aggregates. Simultaneous high-resolution chemical characterization and isotope tracing can be achieved by combining nano-scale imaging mass spectrometry (NanoSIMS) and spatially resolved spectroscopy (STXM/NEXAFS). These techniques allow precise, high-resolution, quantitative measurement of molecular and isotopic patterns in an undisturbed sample.

David Skinner, NERSC
"Science Gateways, Trends in Data-centrism and the Web"
    As data collected from simulations and experiments grows ever larger science teams require reliable and high performance means to analyze data at a distance. The notion of feeling secure about data only when we can hold our own entire copy in personal storage must give way to central shared data storage. This transition in scientific data management affords force multiplying benefits in terms of collaboration. Web based science gateways sited at large scale computing and data facilities can provide a set of methods for remote analysis, data sub-selection, and data sharing for wide ranging data-centric collaboration. In this talk we review the last two years of NERSC's science gateways program and offer ideas for the future of computational bio-imaging at LBL.

September 5, 2012    

Paul Adams, Physical Biosciences Division
Prospects for Using Free Electron Lasers for Crystallography
    Second and third generation synchrotron X-ray sources have had a dramatic impact on the field of structural biology, with the majority of new structures solved annually now coming from experiments performed at synchrotrons. Fourth generation free electron laser (FEL) X-ray sources are now becoming available. What are the potential applications of these radically different machines to structural biology? Recent results from the Linear Coherent Light Source (LCLS) at Stanford will be presented, and some of the potential uses of the Next Generation Light Source (NGLS) will be discussed.

Damir Sudar, Life Sciences Division
"A walk through the LBNL Integrated Bioimaging Center"
    With the Lab's support we have been able to set up in the Potter St. building a working prototype of the ultimate Integrated Bioimaging Center envisioned for the Richmond Bay Campus. I will briefly describe the current capabilities of the Center followed by a tour of the Center which will include a demonstration of the newly acquired OMX super-resolution optical microscope.

June 6, 2012

Bill Jagust, Life Sciences Division, UC Berkeley
"Imaging Neurochemistry and Brain Function"
    Multimodal imaging of the human brain permits the understanding of how neurochemical processes affect brain function. This talk will provide two examples of this approach. One study will examine how brain dopamine affects large scale neural networks and how these networks are related to brain function. The other study will examine how beta-amyloid deposits in the brains of normal older people affect brain function and may permit the presymptomatic detection of Alzheimer's disease.                       

Eva Nogales, Life Sciences Division, UC Berkeley
"Defining Subunit Architecture in Macromolecular Assemblies using EM and Genetic Tags"                      
    Mechanistic understanding of molecular transactions requires knowledge of the architectural organization of the macromolecular machines involved in these processes. Electron microscopy and image reconstruction is becoming a broadly use technique in the structural characterization of macromolecular assemblies. Within EM density maps, localization of specific subunits can be obtained, when recombinant expression system exists for the complex, by the use of genetic tags. In addition to localizing a subunit by tagging one or both of its termini, internal tags are being developed that can allow the effective “tracing” of the polypeptide path of large subunits. I will describe our recent use of such methods in defining the architecture of the eukaryotic proteasome lid subcomplex and the PRC2 gene silencing complex.

May 2, 2012    
Dani Ushizima, Computational Sciences Division

"Image Analysis and Quantitative Evaluation from High-resolution Experimental Data"
    One of the challenges in computer vision is to translate visual inspection into precise mathematical descriptions in order to recognize repeating patterns and automate decision making based on images. Each scientific domain demand adaptations and invention of new algorithms to deal with peculiarities of the data, acquisition-specific issues, to take advantage of high performance computer architectures, etc. This talk will describe image analysis and pattern recognition algorithms applied to diverse and multiscale image databases, ranging from retinal pathology characterization using color photographs, remote sensing using SAR, confocal microscopy of breast cancer, to advanced light source micro-CT of samples for carbon sequestration/storage investigation. We will discuss application of wavelets to the enhancement of reflectivity patterns, mathematical morphology and matched filters to obtain speed functions for propagation of interfaces, a new algorithm for network tracking and pipelines for image analysis.
          Trent Northen, Life Sciences Division                 
          "Imaging Alteration in Lipid Turn-over in Tumors"
    Traditional metabolic profiling methods provide an unbiased analysis of cellular metabolism and have found a diverse range of applications spanning synthetic biology to human health. While these approaches maximize the number of metabolites detected, they depend on solvent extraction methods that result in a loss of spatial information and ignoring much of the inherent complexity of biological systems. Therefore it is critical to complement these profiling methods with small molecule imaging approaches. This talk will present new technologies for mass spectrometry based imaging to study dynamic and spatially defined metabolic processes within the 3D microenvironment.

April 4, 2012   

Bruce Cohen, Molecular Foundry/Materials Sciences Division,
"Next-generation Anocrystals for Imaging:  Non-bleaching, Non-blinking, Anti-Stokes Phosphors"
Manfred Auer
, Life Sciences Division, "Bacterial Social Networks: Multiscale, Multimodal Imaging of Bacterial Communities

Past Events

Mapping the Structural and Functional Architecture of Mammalian Brains.
Special seminar, Thursday, April 24 at 4 p.m. in 125 Li Ka-Shing, UC Berkeley
by Dr. Raju Tomer from Stanford (Deisseroth lab)
Will involve 3D images of transparent brains with the 'clarity' method and light sheet microscopy.

Event Contact:

**Neuro/nano search candidate**
One goal of modern neuroscience is to map the architecture of neural circuits with both high (wiring-level) resolution and broad (brainwide) perspective. This challenge has drawn the attention of generations of scientists, beginning with Cajal’s detailed representations of neurons visualized at high resolution with the Golgi staining technique while still embedded within semi-intact brain tissue. Principles fundamental to the understanding of neural systems can result from such an integrative approach, but while excellent progress has been made, many fundamental challenges and exciting opportunities remain.
In this talk, I will present my work on the development of advanced light microscopy platforms for rapid and high-resolution imaging of intact brains in their entirety, big data informatics, tissue processing and the genetic labelling approaches, to contribute towards the understanding of the structural and functional architecture of the mammalian brains, and their deep evolutionary origins. I will conclude with future perspectives on my continued interest in this field.

Steve Chu Gives Lab Talk on March 31, 2014
Steve Chu, the former director of Berkeley Lab and former Secretary of Energy, will discuss “Optical Microscopy 2.0” as well as the energy/climate challenge. The talk runs from 3 to 4 p.m. in the Building 50 Auditorium, followed by a reception.

Brown Bas Session at NERSC with Jason Swedlow
Jason Swedlow, co-founder of the Open Microscopy Environment (OME), a community-led open source software project that develops specifications and tools for biological imaging, will present on "The Open Microscopy Environment: Open Source Image Informatics for the Biological Sciences"
Wednesday, March 26, 2014 at noon
biography here / abstract here
Location: NERSC, 415 20th St Oakland, CA 94612
Taking BART? Get off at 19th Street Station.
Driving? Park at Kaiser Center Parking Garage at 300 Lakeside Drive, Oakland, CA 94666; parking validation will be provided after the talk.
Attend remotely? Go to: Password: brownbag
Telecon: 866-740-1260 , PIN 4866820
Information: email Joaquin Correa.

Special Bioimaging Initiative Seminar
"Metal-Induced Energy Transfer: Measuring Quantum Yields and Molecular Distances"

Prof. Dr. Jörg Enderlein
III. Institute of Physics, Department of Physics
Georg-August-University Göttingen, Germany
Friday, August 23, 2 - 3 p.m.
At 717 Potter St., room 141

When placing a fluorescing molecule close to a metal structure, one changes the local density of states of the electromagnetic field with profound consequences for the excitation and emission properties of the molecule. In particular, one observes an angular distribution of radiation which is completely different from the molecule in a homogeneous environment, a modification of its emission spectrum, and 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. Recently, we have used this effect to measure absolute values of quantum yield of fluorescing emitters. By placing a solution of the emitters into a metallic nano-cavity and monitoring the lifetime modification as a function of the cavity size, one can determine the radiative and non-radiative transition rates as well as estimate rotational diffusion coefficients. This method is even applicable for complex system showing multi-exponential decay behavior, where it allows for determining the quantum yield of emission for each sub-state separately, or for inhomogeneous mixtures of several emitters, where it allows for obtaining quantum yield values of each emitter species in the mixture. As far as we know, not other existing method is capable of doing that. However, MIET can be used also for localizing fluorescent emitters with nanometer accuracy. 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 to localize, with nanometer accuracy, tubulin molecules above a metallic surface. I will present an extension of this method which we have used 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.

National Center for X-Ray Tomography Featured on KQED QUEST
On KQED TV September 12 at 7:30 p.m., the feature episode in the Bay Area science series QUEST is “Seeing Cells in 3-D,” shot earlier this year at the National Center for X-Ray Tomography at the Advanced Light Source. The center’s director, Carolyn Larabell, and associate director, Mark Le Gros, both of the Physical Biosciences Division (PBD), explain the science behind the x-ray microscope and how it works, displaying spectacular visuals and illustrating breakthroughs in basic biology and health.
Today at Berkeley Lab, September 12, 2012

NGLS Materials & Bioimaging at the Nanoscale Workshop

A day long Materials and Bioimaging workshop will be held Thursday August 30 - Friday Aug 31, 2012 at LBNL. This is one of a series of workshops that is intended to refine the science drivers for Next Generation Light Source and to translate the science needs into performance requirements for the facility.  This includes fundamental Free Electron Laser parameters (e.g. ph/pulse, rep rate, tuning range, pulse duration etc.) as well as requirements for beamlines (photon delivery optics, detectors, lasers etc.) and endstations.  Information from these workshops will be essential input to the development of a preliminary design for the facility.

This is great opportunity to learn more about the potential of the NGLS for biological research and also a chance to provide input and ideas to help shape its development. More details can be found here:

LBNL Integrated Bioimaging Initiative Workshop
February 2, 2012, 8:30 a.m. - 5:15 p.m., LBNL, 717 Potter St., room 141
Host: LBNL Integrated Bioimaging Initiative Organizing Committee. 

9th Annual Advanced Imaging Methods Workshop
January 18 - 20, 2012
Host: University of California Berkeley Molecular Imaging Center
Workshop website.

Workshop: "Flow Cytometry Data Analysis"
August 29, 2011, 2:00 - 3:00 p.m., LBNL, Bldg 977, 717 Potter St., room 141
Learn how to save time turning flow data into results with FCS Express software.
Host: Michelle Scott, Manager Imaging/Cytometry Core Lab

Lecture: "Optical Sectioning Techniques in Light Microscopy"
By Geoffrey Lambright, Carl Zeiss MicroImaging, LLC, 3D Imaging Specialist
July 28, 2011, 3:00 p.m., LBNL, Bldg 977, 717 Potter St., room 141
Lecture followed by open discussion; covers the pros and cons of general sectioning techniques including confocal, 2P, Spinning Disk, TIRF, etc.
Host: Damir Sudar

Seminar: "Advances in Super Resolution Imaging"
"Seeing Biology in High Definition," by Tom Donnelly from Applied Precision Inc., the developers of the DeltaVision and OMX microscopes.
June 14, 2011, 11:00 a.m., LBNL, Bldg 977, 717 Potter St., room 141
Learn about super resolution light microscopy. The seminar is focused on the 3D Structured Illumination Microscopy (3D-SIM) but also addresses PALM, STORM, and associated super resolution techniques. Host: Damir Sudar

LBNL Multiscale Bioimaging Workshop: Towards a Joint Center for Integrated Bioimaging
June 18, 2008, 11:00-5:00 p.m., LBNL, Bldg. 66 Auditorium
Co-Leaders: Jan Liphardt/Manfred Auer                    

Gulliver Multiscale Bioimaging Workshop
May 17-19, 2007, MSRI, Berkeley, CA
The goals of the workshop are to survey some of the cutting-edge advances in microscopy, including novel directions that are still in development, and to plan how we can best accomplish the goals of the Gulliver initiative. The workshop features two days of presentations and discussions focused on the primary application areas (bioenergy and cancer biology). The third day of the workshop is reserved for planning sessions by the participants in the initiative.

Chairs: Damir Sudar, Joe W. Gray, Jay Keasling. The workshop website includes presentation files.