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Biological Sciences

Frontiers in Biological Sciences

The seminar series features nationally/internationally known researchers from industry, government, and academia discussing novel ideas and advancements related to biological sciences. The hour-long seminars will feature a 45-minute talk by the featured speaker followed by 15 minutes of discussion with the audience members.


Yining Huang
Professor Yining Huang

Professor Yining Huang
Department of Chemistry
Western University, London, Ontario, CANADA

Friday, August 29, 2014
EMSL Boardroom (1012)
2:30 p.m.

Solid-State NMR Characterization of MOFs: From Ultra-wideline Spectra of Quadrupolar Nuclei to Ultra-High- Resolution 1H Spectra

One of the most exciting recent advances in the field of porous materials is development of hybrid organic-inorganic solids, or metal-organic frameworks (MOFs). MOFs have high thermal stability, permanent porosity, a flexible framework and exceptionally high surface areas, leading to many important applications.

Although many MOF structures have been determined by single-crystal X-ray diffraction, many others must be refined from more limited powder XRD data because of the lack of suitable single crystals. Further, activation processes such as dehydration and desolvation tend to reduce the crystallinity and lead to fragmentation of single crystals. This requires additional information from complementary techniques, such as solid- state NMR (SSNMR) spectroscopy. SSNMR is sensitive to short-range ordering and local structure, while X-ray probes long-range ordering and periodicity. Together, both techniques provide a more complete picture on overall MOF structure.

Professor Huang will report recent work on multinuclear SSNMR characterization of MOF-based materials.

Anders Jonsson
Anders Jonsson, Ph.D.

Anders Jonsson, Ph.D.
Program Director, BioSoM
Department of Soil and Environment
Swedish University of Agricultural Sciences, Skara

Friday, July 25, 2014
EMSL Auditorium
10:00 a.m.

Biological Soil Mapping of Pathogens – A New Tool in Precision Agriculture

Soil-borne pathogens incite large yield losses. Most of these pathogens produce different types of resting spores that can survive in soils for 10-20 years. In the interdisciplinary BioSoM (Biological Soil Mapping) program, the goal is to develop a new service for the agricultural sector (i.e., farmers, advisers, authorities, researchers) to quantify levels of infestation of pathogens in the field and to give advice concerning crop rotation and management. Swedish University of Agriculture Sciences is responsible for the scientific work and the development of the service in collaboration with selected stakeholders.

Dr. Jonsson’s main research focus is on measurement of soil and product quality. This includes

  • Detection and quantification of leaf and soil-borne pathogens on cereals, legumes, and crucifer crops using molecular methods (BioSoM)
  • Automatic detection of insects in field and storage and rapid methods for measurement of Cd in soil and grain
  • Effects on quality of feed and animal of Mo/Cu and N/S on acryl amide formation.

Stephen Ragsdale
Stephen W. Ragsdale, Ph.D.

Stephen W. Ragsdale, Ph.D.
Professor, Department of Biological Chemistry
University of Michigan Medical School

Wednesday, May 28, 2014
EMSL Auditorium
10:00 a.m.

Biochemistry of Methanogenesis: Mechanism of Methyl-Coenzyme M Reductase

Methanogenesis is responsible for the production of about 1 billion tons of methane per year and accounts for nearly all of the methane found on earth. Methyl Coenzyme M Reductase (MCR), the key enzymatic catalyst in the anaerobic synthesis of methane, also catalyzes the reverse reaction—the oxidation of methane (AOM). This protein is unique to methanogens and anaerobic methane oxidizers. MCR is one of the eight known Ni enzymes that catalyze the utilization and/or production of gases that play important roles in the global biological carbon, nitrogen, and oxygen cycles.

MCR is an unusual enzyme in that it is the only known enzyme that contains a nickel tetrapyrrole (F430). It contains novel post-translational modifications in amino acid residues located at the surface of a 50-Å- long channel that accommodates the two substrates or the products. The active state of the F430 catalyst is a low-valent Ni(I) state and the metal ion appears to traverse three oxidation states (1+, 2+ and 3+) during catalysis. Professor Ragsdale’s lecture will focus on recent studies aimed at deciphering the catalytic mechanism of MCR.

Daniel Segre
Daniel Segrè, Ph.D.

Daniel Segrè, Ph.D.
Associate Professor: Biomedical Engineering, Bioinformatics, and Biology
Boston University

Friday, April 18, 2014
BSF/CSF Darwin Room (1007)
9:00 a.m.

Systems Biology of Microbial Metabolism: from Genomes to Ecosystems

Cellular metabolism consists of a complex network of chemical reactions, which provides the cell with a reliable supply of energy and building blocks. Learning how this network responds to environmental and genetic perturbations is a fundamental open question, relevant for understanding physiological and evolutionary adaptation, for fighting metabolic and infectious diseases, and for metabolic engineering of industrially important microbes. Optimization approaches based on steady state approximations of metabolic networks have become one of the main frameworks for addressing these questions, and one of the flagship methods in systems biology. Professor Segrè will discuss some ongoing applications and challenges in this field, including the integration of regulatory information in metabolic network models, and the extension from individual microbes to natural and engineered microbial communities.

Oliver Fiehn
Oliver Fiehn, Ph.D.

Oliver Fiehn, Ph.D.
Professor, Department of Molecular & Cellular Biology & Genome Center
Director, NIH West Coast Metabolomics Center
University of California, Davis

Monday, March 10, 2014
EMSL Auditorium
10:00 a.m.

The NIH West Coast Metabolomics Center: Integration of Metabolomics Data with Genomics Integration

The National Institutes of Health (NIH) Common Fund has created six U.S.-national metabolomics centers to increase the capacity for metabolomic research for NIH-funded investigators. At UC Davis, the West Coast Metabolomics Center integrates more than 30 mass spectrometers and 5 NMR instruments in eight laboratories, focusing on glycomics, complex lipids, eicosanoids, steroids and lipid mediators, imaging, primary metabolism, and identification of unknowns. In addition, integration with genomic data including pathway mapping and statistics is part of research advancements. The Center currently conducts 12 pilot projects, with additional projects to be decided for 2014. The Center also hosts metabolomic training workshops and has organized three symposia on cancer metabolism, microbial metabolism, and mouse metabolism in its first year.

Professor Fiehn presents advancements in methods, specifically in software and lipid metabolism, that enabled true high-throughput projects with >20,000 samples in >200 projects conducted in 2013. Example projects will be highlighted to show metabolomic data can help formulating hypotheses that are subsequently validated by genomic data.

Christer Jansson
Christer Jansson, Ph.D.

Christer Jansson, Ph.D.
Deputy Program Lead, Bioenergy
Earth Sciences Division
Lawrence Berkeley National Laboratory

Tuesday, February 18, 2014
EMSL Auditorium
1:30 p.m.

Conversion of Carbon Dioxide and Methane to Liquid Transportation Fuels

In Dr. Jansson’s lab, scientists are using synthetic biology and metabolic engineering to develop biological systems for direct conversion of CO2 and CH4 to liquid transportation fuels. He describes two ARPA-E projects: FOLIUM, which aims at establishing tobacco as a platform for foliar production of hydrocarbon fuels; and METHYLASE, which focuses on designing a novel enzyme and metabolic cycle for CH4 assimilation and conversion to fuels.

Dr. Jansson joined LBNL as a Senior Staff Scientist in the Earth Sciences Division in February 2008. Prior to that, he was head of the Department of Plant Biology & Forest Genetics, The Swedish University of Agricultural Sciences in Uppsala, Sweden, where he held the Professor Chair in Molecular Cell Biology from 1999-2008. From 1994-1999, he was Professor in Biochemistry at the Department of Biochemistry & Biophysics, Stockholm University.

His research revolves around plant, algal, and cyanobacterial biochemistry and molecular biology. Specific areas of interest are photosynthesis, carbohydrate and lipid metabolism, and metabolic engineering of plants and cyanobacteria for biofuels and carbon sequestration.

Tim Donohue
Timothy J. Donohue, Ph.D.

Timothy J. Donohue, Ph.D.
Department of Bacteriology
University of Wisconsin-Madison
Director, Great Lakes Bioenergy Research Center

Tuesday, January 14, 2014
EMSL Auditorium
11:00 a.m.

Biological Insights and Products Gleaned from Mining Bacterial Genomes and Pathways

Professor Donohue has been a member of the UW-Madison Bacteriology Department since 1986. His research program studies bacterial energy utilization, specifically how cells divert the energy captured from sunlight or nutrients into different pathways.

He has been a member of numerous federal research panels, has served on several editorial boards and advisory committees in microbiology, has helped author reports for the Department of Energy (DOE) on solar energy generation and the conversion of plant biomass into biofuels, has led cross-disciplinary research programs, including the NIGMS Biotechnology Training Program, and is President-elect of the American Society for Microbiology.

Since 2007, Donohue has been director of DOE’s Great Lakes Bioenergy Research Center, which conducts basic, genomics-based research on microbes and plants to generate knowledge to enable cellulosic biofuels production.

In this lecture, he will present recent insights and products from mining bacterial genomes in work performed inside and outside of Great Lakes Bioenergy.


Janet K. Jansson, Ph.D.
Department of Plant and Microbial Ecology
University of California, Berkley
Ecosystems Biology, Earth Science Division
Lawrence Berkeley National Laboratory

Thursday, December 19, 2013
EMSL Auditorium
10:00 a.m.

Illumination of Impact of Climate Change on Permafrost Microbial Communities

Climate change has unknown consequences for the vast reserves of terrestrial carbon currently sequestered in soil. For example, warming causing thaw of permafrost soil in the arctic, increasing accessibility of previously frozen carbon pools to microbial degradation and greenhouse gas emission. However, study of soil microorganisms is challenging because of the soil microbial diversity and soil matrix complexity. In addition, >90% of soil microorganisms have never been cultivated, and their properties are unknown.

To address this challenge we developed molecular ‘omics approaches that bypass the need for cultivation to gain understanding of the soil microbial community structure and function. We used a combination of deep sequencing of 16S rRNA genes (microbiomics), total DNA sequencing (metagenomics), total RNA sequencing (metatranscriptomics), and shotgun community proteomics (metaproteomics) to determine the impact of permafrost thaw on soil microbial communities and functions in Alaska and to study native prairie soils. In Alaska, we looked at a site undergoing a natural thaw transition and thaw caused by fire, as well as a transect across a site with permafrost deformations, known as polygons. In all cases there were dramatic changes in microbial community composition and function with thaw.

In the prairie we developed a new set of tools to tackle the high microbial complexity and simultaneously determine gene abundance and expression. Results indicate that soil microbial communities are responsive to climate change, and some key processes, including carbon cycling and greenhouse gas emissions, are altered as a result. These data should eventually be used to better inform climate models.

Norman G. Lewis, Ph.D.
Regents Professor and Director
Institute of Biological Chemistry
Washington State University, Pullman, WA

Wednesday, November 6, 2013
EMSL Auditorium
1:00 p.m.

Developing Specialized Phytochemical Factories as Future Sources of Biofuels, Petrochemical Substitutes, Specialty Chemicals, and Medicinals

Engineered plants and microbes, coupled with rapidly evolving synthetic biology approaches, are increasingly viewed as the means to efficiently produce sustainable biofuels, petrochemical substitutes, specialty chemicals, and medicinals. Yet frequently, biochemical pathways to such important target natural products are poorly understood, as are even the cell types (compartments) where they are produced and stored, in the host organism.

In planta, our most important biochemical pathways and products, whether for sustainable commodity/specialty chemicals or structurally complex medicinals, are produced in specialized cell types (phytochemical factories). However, emerging technologies, such as MALDI metabolite imaging/ion mobility spectrometry, laser microdissection of plant tissues, and various omics technologies, now provide incisive means to probe and delineate their underlying processes. This is enabling us to begin to establish and exploit key genes, proteins/enzymes, metabolites, and transport mechanisms, as well as compartmentalization strategies.

Based on such advances, we are now developing sustainable biological platforms in plants for producing key medicinals, and for short-rotation designer woody biomass harboring new biochemical pathways for production of key specialty/commodity/chemicals (e.g., phenylethanol).

Manfred Auer, Ph.D.
Staff Scientist, Life Sciences Division
Lawrence Berkeley National Laboratory

Monday, November 4, 2013
BSF/CSF Darwin Room
9:30 a.m.

Joint seminar with Frontiers in Chemical Imaging

A comprehensive understanding of microbial function requires the spatial/spatiotemporal mapping of macromolecular strategies employed by bacteria in their respective community context. Using different electron microscopy imaging approaches—conventional SEM, 2D- & 3D-(cryo)TEM, as well as Focused Ion Beam (FIB)/SEM and Serial Block Face (SBF)/SEM—we studied four different microbial systems at different levels of resolution and complexity.

I will discuss 1) the termite hindgut microbial community and its lignocellulose-degrading strategies; 2) extracellular metal reduction by and protein expression heterogeneity in sulfate reducer biofilms; and 3) outer-membrane vesicles, vesicle chains, and membrane tubes connecting the predatory, social soil bacterium Myxococus xanthus and its ability to build EPS-based micro-compartments essential for effective colonization. I will also describe ongoing research in my lab on territorial disputes between, for example, Myxococcus xanthus and Bacillus subtilis and the surprising strategies these colonies deploy to deter enemies from invasion.

The overarching theme will be how the combination of faithful cryogenic sample preparation, tag-based labeling, wide-field 2D and large volume 3D imaging, and integration with other imaging modalities, combined with sophisticated image analysis allows us to gain unprecedented insight into microbial community organization and function

Stephen D. Miller, Ph.D.
Judy Gugenheim Research Professor
Microbiology-Immunology, Northwestern University
Feinberg School of Medicine

Monday, April 14, 2013
EMSL 1077
9:15 a.m.

Tolerance-Directed Immunotherapies Employing Biodegradable Nanoparticles for Treatment of Auto(Immune) Diseases

We recently described the ability of the i.v. infusion of 500nm carboxylated biodegradable poly(lactide-co-glycolide) (PLG) nanoparticles covalently linked to autoantigenic peptides (Ag-PLG) to abrogate development of EAE when used prophylactically and more importantly to ameliorate clinical EAE relapses when administered therapeutically suppressing accompanying Th1/Th17 responses, CNS inflammatory cell infiltration and demyelination. Ag-PLG tolerance is dependent on nanoparticle uptake by marginal zone macrophages via the MARCO scavenger receptor which leads to abortive T cell activation as determined by lack of IFN-? or IL-17 production and is the result of the combined effects of anergy and iTreg activation. These findings demonstrate the feasibility of using Ag-NP as a novel, safe and cost-effective platform for antigen-specific therapy of MS and other (auto)immune-mediated diseases. The relationship of specific immunotherapy to disease-specific biomarkers will also be discussed.

Robert L. Sinsabaugh, Ph.D.
Department of Biology
University of New Mexico

Thursday, February 14, 2013
BSF Darwin
10:30 a.m.

Microbial Community Decomposition: Stoichiometry and Carbon Use Efficiency

Carbon use efficiency (CUE) is a fundamental parameter for ecological models based on the physiology of microorganisms. CUE determines energy and material flows to higher trophic levels, conversion of plant-produced carbon into microbial products, and rates of ecosystem carbon storage. Thermodynamic calculations show that the maximum value for microbial growth efficiency is ~0.60. Kinetic and stoichiometric constraints on microbial growth suggest that CUE in multi-resource limited natural systems should approach 0.3. Several methods are used to estimate CUE and the methods applied in aquatic and terrestrial systems generally differ. The methods most often applied to soils may not fully capture the maintenance costs associated with community metabolism, leading to inflated CUE estimates. These difficulties translate to simulation models. Many models lack adequate representation of energy spilling pathways and stoichiometric constraints on metabolism, which may lead to overestimates of CUE.

We recommend that broad-scale models use a CUE value of 0.30, unless evidence suggests pervasive nutrient limitations. Models operating at finer time scales should consider resource composition, stoichiometric constraints and biomass composition, as well as environmental drivers, to predict the CUE of microbial communities.

Justin P. Gallivan, Ph.D.
Department of Chemistry
Emory University, Atlanta, GA

Monday, February 11, 2013
BSF Darwin
9:00 a.m.

Synthetic Riboswitches for Controlling Bacterial Gene Expression

Riboswitches are messenger RNA sequences that control gene expression in a ligand-dependent fashion, without the need for protein cofactors. Riboswitches recognize their ligands using aptamers, which may be discovered through in vitro selection. Incorporating novel aptamers into synthetic riboswitches provides powerful opportunities for modulating gene expression for applications in metabolic engineering and synthetic biology. Dr. Gallivan will present results from recent mechanistic studies that not only provide new insights into riboswitch function, but also suggest strategies for discovering riboswitches that respond to novel ligands.


Kristen Naegle, Ph.D.
Washington University in St. Louis

Thursday, November 8, 2012
CSF Mural Room
Noon - 1:00 p.m.

Joint Signatures and Frontiers in Biological Sciences Seminar

Ensemble Clustering of Phosphorylation Dynamics Reveals Novel Interactions in the ERBB Network

Receptor tyrosine kinase networks, such as the ERBB family of receptors, rely heavily on tyrosine phosphorylation for propagation of cellular signals. Mass spectrometry techniques have led to a rapid increase in the discovery and observation of phosphorylation dynamics within the cell, which has outpaced our ability to understand the role of individual phosphorylation sites within the network. Dr. Naegle shows how ensemble clustering of dynamic phosphorylation data has been useful in identifying novel network interactions. The combination of machine learning and molecular measurements has produced insight regarding transient, protein-protein interactions, which no other traditional molecular screens would likely have captured.

Jack D. Griffith, Ph.D.
Kenan Distinguished Professor of Microbiology and Immunology and Biochemistry
University of North Carolina School of Medicine

Tuesday, October 23, 2012
EMSL Auditorium
11:30 a.m

Joint Seminar with Frontiers in Catalysis Science and Engineering

Electron Microscopic Visualization of Telomeres, DNA Repair Factors, and Nanoparticles Bound to Cells

High-resolution electron microscopy provides a unique window into the architecture of DNA and DNA-protein complexes. In our studies of the ends of chromosomes (telomeres), we have shown that human chromosomes end in giant duplex loops. The telomeric factors and DNA repair factors involved will be described and EM and biochemical studies used to illustrate how these factors are central to both cancer and aging.

A new approach using cryo methods combined with freeze drying and high-resolution metal coating is providing an exciting means to visualize cell structures including actin networks and nanoparticles being taken up by cells. The method and applications will be discussed.

Lance C. Seefeldt, Ph.D.
Professor of Chemistry and Biochemistry
Utah State University

Wednesday, July 18, 2012
EMSL 1077
11:30 a.m.

CO2 Reduction and Coupling to Hydrocarbons Catalyzed by Nitrogenase

The enzyme nitrogenase catalyzes the six electron/proton reduction of N2 to form 2 NH3. In addition, the enzyme also catalyzes the reduction of protons to make H2. Professor Seefeldt's lab has discovered that when amino acids close to the active metal cluster FeMo-cofactor are substituted to remodel the active site, nitrogenase can reduce CO2 to CH4. He will further demonstrate that CO2 reduction can be coupled with acetylene reduction to give the olefin propene, thereby providing a pathway for conversion of CO2 into valuable hydrocarbons with a single catalyst. Recent evidence indicates the importance of metal-hydrides in the nitrogenase mechanism. Professor Seefeldt will discuss the possible involvement of metal-hydrides in CO2 reduction and present a draft mechanism for N2 reduction.

Lauren J. Webb, Ph.D.
Department of Chemistry and Biochemistry
University of Texas at Austin

Tuesday, July 17, 2012
EMSL 1077
9:15 a.m.

Electrostatic Fields at Biological Interfaces

In the post-genomic era, enhanced understanding of the cooperation between biological molecules is necessary to explore the complexity of living cells. The affinity and specificity of macromolecular interactions in biological systems are the result of both structural and electrostatic driving forces, but while the field of structural biology has made great advances, much less is understood about electrostatic influences.

Professor Webb will describe how vibrational spectroscopy can be used to measure electrostatic fields in two complex biomolecular systems: 1) stable protein-protein interfaces and 2) peptides intercalated in free-standing lipid bilayer membranes. Her laboratory is developing computational models that accurately predict these interactions using vibrational Stark effect (VSE) spectroscopy, in which spectral shifts of a probe oscillator's energy are related directly to that probe's local electrostatic environment.

Professor Yi Lu
Department of Chemistry
University of Illinois at Urbana-Champaign

May 11, 2012
BSF Darwin Room
9:30 am

Joint seminar with Frontiers in Catalysis Science and Engineering

Rational Design of Metalloproteins as Biocatalysts for Sustainable Energy: Exploring Roles of Non-covalent Interactions in Conferring Enzymatic Activities

Metalloproteins play critical roles in sustainable energy, such as in photosynthesis, biomass conversion, biofuel cells and water splitting or oxidation. These proteins cannot be used in practical applications due to high cost and low stability, while cost-effective and stable biomimetic compounds can be very difficult to reproduce either the structure or function of the proteins. To overcome these limitations, we have been using small, stable, easy-to-produce and well characterized proteins as "ligands" to make biosynthetic models of metalloproteins, such as cytochrome c oxidase, a terminal oxidase that can convert the energy in O2 into proton gradient as a form of biofuels, and manganese peroxidase, an enzyme that can degrade lignin, a critical step in biomass conversion. In this presentation, I will give recent examples to demonstrate that non-covalent interactions around the active site of proteins, such as hydrophobic tuning and hydrogen-bonding network and well-positioned water are required to make structural and functional models of these important metalloproteins with high reactivity and turnovers.

Wuhan Center for Magnetic Resonance
Wuhan Institute of Physics and Mathematics
Chinese Academy of Sciences

Research at the Wuhan Center for Magnetic Resonance

Monday, April 23, 2012
EMSL Boardroom
1:00 p.m.

Each professor will describe research at the Wuhan Institute's Center for Magnetic Resonance, including:

Solid-state NMR spectroscopy and theoretical DFT calculations studies of solid acid catalysts and catalytic reactions. With the increasingly intense demands for environmentally friendly processes in the chemical and petroleum industries, solid acid catalysts (zeolites, heteropoly acids, complex metal oxides) offer new alternatives to the highly corrosive, hazardous and polluting liquid acids (HF, H2SO4). The acidity of solid acid catalysts is closely related to their catalytic activities. In this presentation, recent work at the Wuhan Center on characterization of the acidity of solid acid catalysts and related catalytic reactions by solid-state NMR spectroscopy and DFT calculations will be introduced.

  • NMR approaches for bio-analysis. Approaches developed recently in at the Center for analysis of biological samples include:
  • Solvent signal suppression using WATERGATE
  • Selective detection of choline contained metabolites in tissue using 1H-14N HSQC
  • GFFT for processing non-linear acquired nD NMR data and NASR for suppression noise and artifacts
  • An effective approach to characterize individual variation of human blood plasma and application to protein-drug interaction.

Jennifer DuBois, Ph.D.
Associate Professor of Chemistry and Biochemistry
University of Notre Dame

Monday, February 20, 2012
BSF/Darwin Room
10:00 a.m.

From O-O bond formation to Fe metabolism: the story of a new bacterial protein superfamily

Bacteria have a remarkable capacity for change. Several genera of bacteria have been discovered that have evolved the ability to respire and thereby detoxify oxochlorates: biocides and oxidants of recent anthropogenic origin that are a particular problem at DOE sites. The respiratory pathway concludes with a biologically unusual and chemically challenging reaction: the conversion of chlorite (ClO2-) into Cl- and O2. This heme-dependent reaction provides a remarkably efficient model for catalyzing O-O bond formation, a reaction of current interest for clean energy research. At the same time, the protein is one of a quarter of the approximately 5700 unicellular clusters of orthologs (COGs) that still lacks any defined biological function.

Our research into understanding the proteins at the forefront of this COG's evolution has now led us back into an exploration of their origins, and the broader biological relevance of the family from which the O2-generating proteins evolved. Specific functional links of the COG to heme and nitrogen metabolism have been discovered through genetic and biochemical means. Structural and informatics analyses have further shown that these proteins are part of a previously unrecognized structural superfamily of proteins, called the CDE superfamily.

Patrick S. Chain, Ph.D.
Patrick S. Chain, Ph.D.

Patrick S. Chain, Ph.D.
Metagenomics and Next Generation Sequencing (NGS) Applications Team Leader
Los Alamos National Laboratory

Wednesday, February 1, 2012
BSF/Crick Room
9:00 a.m.

Sequencing microbial communities: progress and challenges

The increased throughput of next-generation sequencing platforms has opened the door to a number of sequencing applications that were not fathomable even a few years ago. While the increased sequencing capacity has enabled the interrogation of microbial consortia of varying diversities, the tremendous amount of data generated has required new data management practices and the development of novel algorithms and tools to adequately analyze the resulting sequences. The constantly changing landscape in sequencing throughput and platforms continues to challenge our ability to process the data (including common practices such as assembly and annotation). In this presentation, some of these challenges will be discussed, along with novel methods adapted for large datasets derived from microbial communities. In particular, the challenge of metagenome assembly will be presented, along with the use of reference genomes, and efforts to improve single cell genomics methods to more adequately obtain near-complete references for a target environment.


Trent R. Northen, Ph.D.
Principal Investigator, Molecular Cartography Project
Lawrence Berkeley National Laboratory

Friday, November 4, 2011
EMSL Auditorium
9:30 a.m.

Mass spectrometry-based metabolite profiling and imaging

Metabolite profiling using mass spectrometry provides an attractive approach for the interrogation of metabolic capabilities from complex biological systems. Untargeted metabolite profiling using electrospray ionization has the potential to improve functional genome annotations, characterize uptake and release of metabolites, and study the effects of low-dose ionizing radiation. However, conventional methods are slow, and de novo identification of metabolites from spectral features remains a challenge given the large number of experimental artifacts.

In this talk, Dr. Northen will present an integrated workflow for metabolite identification, characterization of uptake/release, fate, and metabolite/activity screening. This was done using uniform stable isotope labeling for chemical formula determination, structural analysis using MS/MS spectra vs. spectral database records, and systematic screening of consumed or excreted metabolites using metabolite profiling of growth media from microbial cultures (referred to as metabolic footprinting).

They have performed systematic evaluation of intracellular and extracellular metabolites on the model cyanobacterium Synechococcus sp. PCC 7002. It was found that 102 out of 202 detected metabolites were exchanged significantly and the fate of uptake several metabolites were determined using stable isotopic labeling. He will also present applications of nanostructure-initiator mass spectrometry (NIMS) technologies for imaging and screening glucoside hydrolase activities.

Jian Xu, Ph.D.
Professor and Director, BioEnergy Genome Center
Chinese Academy of Sciences
Qingdao Inst of BioEnergy and Bioprocess Technology

Tuesday, September 13, 2011
BSF Darwin Room
9:00 a.m.

Genetic Foundation for Robust Production of Oil in Microalgae

Microalgae are considered one promising feedstock for photosynthetic biofuels. However, the genetic diversity and genomic evolution of microalgal traits relevant to oil production remain elusive. Nannochloropsis is a genus of planktonic unicellular microalgae that lack chlorophyll b and c. Many strains of this genus are capable of growing rapidly and producing large amounts of neutral lipids mainly in a form of triacylglycerol (TAG). We have developed a Phylo- Genomics approach to investigate the genetic diversity and genomic evolution of oleaginous microalgae using Nannochloropsis as a model. First, a high-quality draft genome sequence of Nannochloropsis oceanica has been generated using a hybrid sequencing and assembly strategy that combines the powers of pairended reads from 454 and Solexa. Second, transcript sequencing was applied to reconstruct the global diversity and dynamics of gene expression under various pivotal environmental conditions that lead to robust accumulation of TAG in N. oceanica. Third, draft genome sequences of representatives of other known Nannochloropsis species, including N. salina CCMP537, N. gaditana CCMP527, N. sp. CCMP531, N.oculata CCMP525, N.limnetica CCMP505 and N.granulata CCMP529 were obtained. Together, these Nannochloropsis genomes decoded span a wide phylogenetic range. The genome sizes are all between 20Mb to 35Mb; however, the sequence diversity and genome-structure divergence of these species/strains vary widely. In this presentation, the conservation and divergence of genes, regulatory elements and metabolic pathways in Nannochloropsi, particularly those for oil production, will be described. Furthermore, the implications of the high-throughput functional genomics approach for developing new-generation algal feedstocks will be discussed.

Claudia Schmidt-Dannert
Claudia Schmidt-Dannert

Claudia Schmidt-Dannert, Ph.D.
Department of Biochemistry, Molecular Biology and Biophysics
BioTechnology Institute, University of Minnesota

August 8, 2011
BSF Darwin Room
12:00-1:00 p.m.

Building Better Microorganisms for Biotechnology

Advances in 'omics and genetic engineering have led to the emergence of the field of synthetic biology, which aims to reengineer and synthesize biological systems at much larger scales than manipulating one gene at a time. Reprogramming and rewiring biological systems by introducing new functionalities offers great promise for the design of cells to produce new chemicals, bioenergy, and biofuels.

Dr. Schmidt-Dannert will discuss and show examples of efforts on engineering new complex properties into microbial cells. She and her colleagues are studying the possibility of engineering non-photosynthetic cells for the conversion of light energy into useful chemical energy or electricity. She will present their efforts to engineer light-driven electricity generation into Shewanella oneidensis. Concentration and sequestration of toxic metabolites inside bacterial cells is another highly desirable feature to be introduced into microbial workhorses. Being able to compartmentalize metabolic reactions would, for example, enable efficient CO2 capture and corsion, increase flux through engineered pathways, and prevent accumulation of toxic pathway intermediates.

Her lab has recently engineered micro-compartments in E. coli for targeted enzyme localization, and she will present some of their results on the creation of such in vivo nano-bioreactors. She will also provide a look at current work in the area of synthetic ecology where she and her colleagues aim to design microbial communities for task sharing in the production of metabolites such as biofuels.

Leigh Anderson
Leigh Anderson

Leigh Anderson, Ph.D.
CEO, Plasma Proteome Institute
and Applied Chemistry

Poster: "The Diagnostic Proteome: Challenges and Opportunities in the Discovery and Clinical Implementation of Protein Biomarkers"

Friday, July 15, 2011
EMSL Auditorium
11:00 AM

The current clinical plasma proteome consists of 109 proteins measured by FDA-cleared or approved assays and 96 proteins measured using widely available laboratory developed tests, ~1% of the baseline human proteome. However the rate at which new protein analytes achieve FDA approval has remained essentially constant over the past 15 years at 1.5 proteins per year, insufficient to meet medical needs. The striking shortfall in new protein diagnostics emerging from proteomics research reflects a lack of critical biomarker verification capacity.

To bridge the gap between biomarker discovery and clinical use, a new approach to verification is described: multiplexed panels of specific candidate assays based on hybrid immuno-mass spectrometric (SISCAPA) detection. By combining high sensitivity, high throughput, and precision with use of small plasma samples, a platform for systematic verification of hundreds of candidates in thousands of samples can be implemented. In the clinical laboratory, affinity enrichment with MS quantitation can provide absolute specificity, true internal standardization, and facile multiplexing—thus transcending the limitations of conventional immunoassays. An extension of this approach, the hPDQ project providing a library of specific tests for all 21,300 human proteins, could provide the larger biomedical research community with direct quantitative access to the entire human proteome.

Terry C. Hazen
Terry C. Hazen

Terry C. Hazen, Ph.D.
DOE BER Distinguished Scientist
Head, Ecology Department
Head, Center for Environmental Biotechnology
Director, Microbial Communities, Joint BioEnergy Institute
Co-Director, Virtual Institute Microbial Stress and Survival
Earth Sciences Division, Lawrence Berkeley National Laboratory

June 13, 2011
EMSL Auditorium
11:15 a.m.- 12:15 p.m.

A Systems Biology approach to the Deepwater Horizon Oil Spill—An example of team science for ecological disasters

The explosion on April 20, 2010, at the British Petroleum-leased Deepwater Horizon drilling rig in the Gulf of Mexico off the coast of Louisiana resulted in oil and gas rising to the surface and oil coming ashore in many parts of the Gulf. It also resulted in an immense oil plume 4,000 feet deep. Despite spanning more than 600 feet in the water column and extending more than 10 miles from the wellhead, the dispersed oil plume was gone within weeks after the wellhead was capped—degraded and diluted to undetectable levels.

Ecogenomics enabled discovery of new and unclassified species of oil-eating bacteria that apparently lives in the deep Gulf where oil seeps are common. Using 16s microarrays, functional gene arrays, clone libraries, lipid analysis, phenotypic microarrays, metagenomes, metatranscriptomes, single cell sequencing, and stable isotope analysis in combination with a variety of hydrocarbon and micronutrient analyses, scientists were able to characterize the deep-sea microbial ecosystem and the effect of the oil spill. This team-science approach suggests a great potential for intrinsic bioremediation of oil plumes in the deep-sea and other environs in the Gulf of Mexico.

Caroline M Ajo-Franklin
Caroline M Ajo-Franklin

Caroline M Ajo-Franklin, PhD
Staff Scientist, The Molecular Foundry
Lawrence Berkeley National Laboratory

June 6, 2011
CSF Mural Room (1508)
1:30 - 2:30 p.m.

Interfacing Living Cells and Inorganic Materials at the Nanoscale

Dr. Ajo-Franklin's research group uses synthetic biology, biophysics, and nanoscience to engineer and understand the functional interface between living cells and inorganic materials at the nanoscale. By directly interfacing living organisms with synthetic materials, scientists can harness the vast capabilities of life in photo- and chemical energy conversion, chemical and material synthesis, and self-assembly and repair.

She will describe their efforts to engineer electronic communication between biological cells and inorganic materials and our efforts to understand how living cells can influence mineralization of inorganic materials. These efforts illustrate how scientists seek to understand and control nanoscale processes at the cellular-inorganic surface so to engineer cells to become self-replicating, programmable "living materials."

Eleftherios (Terry) Papoutsakis
Eleftherios (Terry) Papoutsakis

Eleftherios (Terry) Papoutsakis, PhD
Department of Chemical Engineering, Department of Biology
Delaware Biotechnology Institute
University of Delaware, Newark, DE

June 1, 2011
EMSL Auditorium
1:15 - 2:15 p.m.

Systems Analysis and Metabolic Engineering of Solventogenic Clostridia

Clostridia are anaerobic, endospore-forming prokaryotes of major importance to cellulose degradation, human and animal health, and acidogenesis, with several applications in biotechnology and advance bioremediation. Clostridial genetics and biotechnology have been frequently misunderstood or ignored. In the last 5 years, however, there has been enormous growth in clostridial-based industrial processes. For example, solventogenic clostridia can produce a large array of metabolites, while metabolic engineering could enhance these native capabilities for production of additional chemicals. Such chemicals can serve as biofuels directly or indirectly.

Dr. Papoutsakis will review the origin and successes in metabolically engineering and some of the systems biology work on solventogenic clostridia, and will highlight recent developments in his lab in modifying their sporulation program. The goal of these "differentiation engineering" efforts is to generate solventogenic but non-sporulating strains suitable for intensive, continuous or semi-continuous bioprocessing. Dr. Papoutsakis will also highlight recent work in his lab to understand core regulons and the stress response system in these organisms.

Dr. Krishna Mahadevan
Dr. Krishna Mahadevan

Department of Chemical Engineering
and Applied Chemistry
University of Toronto

Poster: "Integrated Modeling of Microbial Ecology in Subsurface Environments"

Thursday, May 12, 2011
BSF Darwin (1007)
8:30 AM

Recent advances in experimental and computational technologies have enabled the detailed characterization of biological systems. In particular, the molecular components of these systems, including the list of genes, proteins they encode, and compounds that interact with these proteins, can be determined. This availability of tools to analyze system-wide changes at the gene, protein, and metabolite level has created significant opportunities to understand cellular functions resulting in the emergence of systems biology. Specifically, constraint-based modeling approach has proven successful in predicting the physiology of well-studied and poorly characterized microorganisms.

Dr. Mahadevan will give an overview of a constraint-based modeling approach and recent developments in this area, including limitations, and discuss the development of metabolic models for environmentally relevant bacteria and their use in optimizing practical applications in electricity generation and bioremediation. Finally, he will present extensions of this approach for analyzing microbial ecology in the subsurface; specifically, using genome-based approaches to study the competition dynamics between different species of iron-reducing bacteria critical for uranium bioremediation. Results provide an improved understanding of factors controlling growth and respiration of the microbial population and their impact on bioremediation in heterogeneous environments.

Dr Joe GrayDr. Joe Gray
Director, Center for Spatial Systems
Oregon Health & Science University

Poster: "A Systems Approach to Breast Cancer—Carcinogenesis to Therapy "

Monday, April 18, 2011
EMSL Auditorium, Richland, WA
1:00 PM

Dr. Gray's laboratory explores mechanisms by which genomic, transcriptional, and proteomic abnormalities occur in selected cancers; elucidates how these abnormalities contribute to cancer pathophysiology; and assesses the ways in which these abnormalities influence responses to gene-targeted therapies. Current studies focus on developing (a) genome-wide analyses of the spectrum of recurrent abnormalities that influence cancer behavior, (b) systems biology approaches to elucidate mechanisms by which cancer-associated molecular abnormalities influence individual responses to therapeutic inhibitors, (c) siRNA approaches to treat breast or ovarian cancer subpopulations that do not respond well to current chemotherapy, and (d) strategies for early detection of metastasis-prone breast cancer.

Poster: "New Tools for Biological Imaging: Correlated Cryo Fluorescence Microscopy and Soft X-ray Tomography "

Monday, April 19, 2010
EMSL Auditorium, Richland, WA

Dr. Larabell's lab is at the forefront of developing soft x-ray tomography as a new tool for visualizing the location of proteins in cells and for imaging sub-cellular architecture with a spatial resolution of 40 nanometers or better. This new imaging technique combines many of the advantages of both light and electron microcopies, with characteristics unique to x-ray imaging. Her lab has designed and built the world's first soft x-ray microscope for biomedical imaging at the Advanced Light Source at Lawrence Berkeley National Laboratory.

Previous Seminars

Poster: "Integrated Molecular Approaches to Study Microbial Ecology and Evolution in an Acid Mine Drainage-Based Model System"

Highlight: Modeling Microbes and Minerals

Friday, March 19, 2010
EMSL Auditorium, Richland, WA

Dr. Banfield's research group studies interactions between microorganisms and minerals, especially the impact of microorganisms on mineral weathering and crystal growth, biomineralization, and geochemical cycling. In this seminar, she will describe a highly productive ecosystem in an extreme natural environment that is supported by air, water, and iron sulfide minerals. Through integrating cultivation-independent molecular ('omic, 3-D electron tomography, and other) methods with geochemical approaches, it has been possible to begin to determine how these communities are structured and to unravel complex interdependencies, spatial organization, and evolutionary pathways.

Poster: "Developing Genome-Enabled Sustainable Lignocellulosic Biofuel Technologies at the Great Lakes Bioenergy Research Center"

Presentation: "Developing genome-enabled sustainable lignocellulosic biofuels technologies"

Highlight: Building Better Biofuels

Tuesday, November 10, 2009
EMSL Auditorium, Richland, WA

Dr. Timothy Donohue, Professor of Bacteriology, University of Wisconsin-Madison

Professor Donohue has been a member of the UW-Madison Bacteriology Department for more than 20 years. His research program studies solar energy use by photosynthetic bacteria; specifically, how cells divert the energy captured from sunlight into different pathways. He has been a member of various federal research panels, served on several editorial boards and advisory committees in microbiology, and helped author reports for the Department of Energy on solar energy generation and the conversion of plant biomass into biofuels. He has decades of experience in leading cross-disciplinary research programs, including the NIGMS Biotechnology Training Program.

In 2007, Dr. Donohue was named director of the new Department of Energy-sponsored Great Lakes Bioenergy Research Center (GLBRC). The Center conducts basic, genomics-based research to design the microbial and plant systems needed to realize the potential of biofuels. In particular, GLBRC programs are focused on the sustainable conversion of cellulosic and other plant biomass into ethanol or other next-generation biofuels.

Combining innovative science, a critical mass of natural assets, and the corporate horsepower to build and advance a new bioenergy economy, Great Lakes Bioenergy is position to become a worldwide center of excellence for R&D of cellulosic ethanol and other bioenergy products. In support of this vision, GLBRC activities are being led by academic, national lab, and industry experts in plant biology, microbiology, molecular or cell biology, biochemistry, protein design, engineering, computer sciences, systems analysis, and ecology.

"Making Second-Generation Biofuels from Biomass Materials: Current Status and Future Perspectives"

Monday, March 23, 2009
EMSL Auditorium, Richland, WA

Dr. Birgitte Ahring, Director of the Center for Bioproducts and Bioenergy and Battelle Distinguished Professor, based at WSU Tri-Cities, was the presenter.

Dr. Ahring has been Director of the Center for Bioproducts and Bioenergy at WSU-Tri-Cities' Bioproducts, Sciences, and Engineering Laboratory (BSEL) since August 2008. Previously, she was professor at The Technical University of Denmark in Lyngby. She is an internationally recognized authority in using anaerobic bacteria—bacteria that exists in an oxygen-free environment—to biodegrade waste.

Dr. Ahring's diverse background includes public-private partnerships, academic and industrial collaboration, high-level research, and a passion for educating others. She received her Ph.D. in microbiology in 1986 from the University of Copenhagen.

She also is founder and Chief Executive Officer of BioGasol, an engineering and technology company that designs and develops technologies for second-generation bioethanol production. Her company is a partner in the Pacific Northwest's first ethanol plant, which is funded with $24 million by the U.S. Department of Energy. This plant is being built in Boardman, Ore., about 70 miles southwest of WSU Tri-Cities.

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