The Viral Information Institute

VII Participants

Matthew Anderson, Optical methods to probe biological and environmental processes (Physics Department)

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Matt Anderson’s research centers on the physics of ultrashort pulsed laser light. He built the first (and only) femtosecond laser system at SDSU, and over the last several years has used this system to study the limits on pulse shaping and measurement, nonlinear effects in matter, and generation of novel femtosecond beams using spatial light modulators. These areas of research have been at the forefront of optical science for the last decade. Dr. Anderson’s current interests are the generation and measurement of femtosecond vortex beams with applications to microfluidics, and using femtosecond lasers in two-photon microscopy with applications in neuroscience and environmental community ecology. In collaboration with the Rohwer lab, Matt Anderson has improved optics-based area detectors of oxygen, known as optodes, for monitoring algae on coral reefs. Dr. Anderson has recently assembled an optical tweezer set-up, which can be used to study the properties of nucleic acids and the proteins that modulate their structure.

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Arlette Baljon, Large-scale simulations of biopolymers (Physics Department)

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One example of an associating polymer network is mucus.  Using large scale modeling, my group investigates if and why the adherence of phage to mucins helps them to hunt for bacteria. This work is in collaboration with other researchers in the Viral Information Institute (Human Health).

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Jeremy Barr, Phages and mucosal surfaces (Biology Department)

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Jeremy Barr’s research utilizes a mix of classical phage techniques combined with tissue culture, microfluidic devices, and high-speed microscopy. He recently proposed the Bacteriophage Adherence to Mucus (BAM) model, whereby bacteriophages provide a ubiquitous, but non-host-derived immunity applicable to mucosal surfaces. Jeremy’s research has led to further work detailing a subdiffusive mechanism that phages utilize as a search strategy to effectively hunt for bacterial hosts in mucus layers. Jeremy is continuing his research on phages and mucosal surfaces, and is further developing commercial applications from these discoveries.

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Liz Dinsdale, Expanding the exploration of unknown biospheres (Biology Department)

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Liz Dinsdale combines her ecological, statistical, and metagenomics expertise to probe unstudied or poorly studied environments such as the Oxygen Minimum Zones in Chile, comparisons of coral reefs and kelp forests, and “emerging environments” that arise where different ecological communities come together, such as coral reefs and kelp forests. Oxygen minimum zones (OMZs) in the ocean are increasing dramatically and affect ocean productivity and fluxes of greenhouse gases. Low oxygen zones become dominated by microbes, whose metabolism contributes to the flux of greenhouse gases. In geological times, anoxic oceans correlated with massive extinction events. Dinsdale and colleagues have found that, while viruses are abundant in the OMZs, the viruses are extremely divergent from viruses in other environments. Within the anoxic core, viruses are in low abundance and diversity suggesting that anoxic environments may be a location where viruses change lifestyle strategies. Investigating these environments is critical, as similar OMZs are developing in many other areas around the globe, and their influence on the global climate is important to describe and quantify. Liz Dinsdale has led the development of statistical analytic strategies for probing the functional and taxonomic diversity of metagenomes with co-authors Barb Bailey from Math & Stats and Rob Edwards from Computer Sciences.

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Rob Edwards, Spearheading computational analyses of genomes & metagenomes (Computer Science Department)

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The vast amount of sequence available has required continuous creative and high-powered application of computer science-driven analyses. Rob Edwards has applied his unique combination of microbiology and computer science approaches to more “classical” genomics long before the advent of metagenomics, as evidenced by his >9300 citations. His lab has developed a plethora of tools critical for the processing and the interpretation of the large sequence datasets now pouring out from experimental labs. His long-standing participation and collaboration with the computational group now based at Argonne National Laboratory resulted in the development of the RAST and MG-RAST genome annotation tools. Rob Edwards and Forest Rohwer together proposed and published a protein-based phylogeny of viruses, which provided novel insights into viral genomics and evolution. While initially controversial, this work has become the de facto strategy of comparing viral genomes, particularly in the phage community. The Edwards lab continues to roll out tools essential for the analysis of metagenomic data. Funding: NSF

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Marina Kalyuzhnaya, Methane biocatalysis (Biology Department)

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Methane is a critical component of Earth's carbon cycle that is causing up to 20% of the Earth’s warming. CH4 is emitted from a variety of natural and anthropogenic sources. Biological methane conversion is the main mechanism that controls the methane flux in nature and, if applied to human-made systems, could offer a sustainable approach for global warming stabilization and the possibility of reduction.  Research in Dr. Kalyuzhnaya group is centered on two primary challenges in microbiology: gaining a better understanding of the  functional capabilities of methane-consuming microbes in nature and applying the newly discovered principles to the development of novel sustainable technologies. The research extends from the characterization of key elements (enzymes, regulators) essential for microbial methane utilization to the elucidation of the spatial organization, evolution, and functional plasticity of the related functions, and from metabolic modeling of C1-biocatalysis to construction of novel microbial traits for biotechnological applications.

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Antoni Luque, Structural and ecological modeling of viruses (Mathematics & Statistics Department)

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Antoni Luque’s research spans the areas of theoretical and computational biophysics and has focused on the study of viruses and chromatin fibers. He has investigated these macromolecular systems by combining condensed matter physics, applied mathematics, and computational biology in collaboration with experimentalists. His aspiration in the Viral Information Institute is to develop multiscale mathematical and computational models to understand the impact of the molecular structural properties of viruses in viral ecology.

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John Mokili, Virus Discovery (Donald P. Shiley Bioscience Center, College of Science)

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The metagenomic technology has revolutionized the field of Virology by allowing with relative ease the discovery of a vast array of novel viruses in various environmental, animal and human samples. Using his experience in virus discovery, John Mokili is spearheading his research toward the studies the etiology of diseases with unknown origin. Current John Mokili’s research focuses on the characterization of the virome in blood, feces, cerebrospinal fluids collected from patients suffering from nodding syndrome in remote African villages. The viral population in these samples will be compared with those of healthy individuals and blackflies (Simulii sp., suspected vector of nodding syndrome). The data collected in this research will eventually lead to determining the cause of nodding syndrome. In addition, in collaboration with Rob Edwards (Computer Science) and colleagues at UCSD, John Mokili’s laboratory is exploring new territories in the search of the etiology of colorectal cancer using viral metagenomics, proteomics and metabolomics.

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Byron Purse, Organic synthesis of probes of cellular functions (Chemistry Department)

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Byron is a organic synthetic chemist with expertise in designing and synthesis of novel probes of biological processes, with emphasis on fluorescent nucleotides permitting monitoring of replication. Byron will contribute his expertise to developing new or improving existing probes for biological processes.

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Forest Rohwer, At the forefront of viral metagenomics (Biology Department)

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Forest Rohwer is a Fellow of the American Academy for Advancement of Science (AAAS), American Academy of Microbiology (AAM) and Canadian Institute for Advanced Research (CIFAR). He led the development of “viromics”, which involves isolating and sequencing the RNA/DNA from all of the viruses in an environmental sample. From this data, it is possible to determine what types of viruses are present and what functions they are encoding. Dr. Rohwer uses viromics to study ecosystems ranging from coral reefs to the human body and has shown that most genomic diversity on the planet is viral. Dr. Rohwer has published >150 peer-reviewed articles, two books, was awarded the International Society of Microbial Ecology Young Investigators Award in 2008 and listed as one of the World's Most Influential Scientific Minds (Thomson Reuters 2014).

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Peter Salamon, Mathematical modeling, optimization, machine learning, math crusader (Mathematics & Statistics Department)

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Peter Salamon, with his research associates Ben Felts and Jim Nulton (both long-term adjunct faculty at SDSU), have created mathematical modeling tools to make sense of metagenomic data and express in quantitative terms the biological description of different environments. Their mathematical tools have been critical to insightful analyses not possible without them, and his collaboration with Forest Rohwer has been instrumental in revealing the power of metagenomics as an approach to microbial ecology and evolution with applications to both human and environmental health. Peter’s expertise in artificial neural networks has permitted developing novel algorithms to predict the function of viral genes that are not similar to any genes with known function. These algorithms are much more sensitive to very subtle functional signatures that are presently not detected by the traditional algorithms such as BLAST. The predictions made by the neural networks have been validated by the Segall lab or with external collaborators using electron microscopy and crystallography, respectively.

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Anca Segall, Genetic and biochemical investigations of gene function and mechanisms (Biology Department)

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Together with Forest Rohwer, Anca Segall helped develop strategies for using sequencing-based methods to probe whole communities rather than single cells or viruses. She and Peter Salamon initiated the use of artificial neural networks to more sensitively probe and predict the function of genes without known function. She combines her genetic expertise, which includes modern recombineering technologies, with biochemical and cell biology assays to validate the predictions made by the newly developed neural network. She and her colleagues have combined computational, electron microscopy, and crystallographic approaches, to identify the function of over 4% of genes in the publically available metagenomes. The Segall lab collaborates with Suckjoon Jun (UCSD), with the SDSU MEMS Lab in Engineering, headed by Sam Kassegne, and with Peter Salamon, to follow bacterial growth and responses as well as interactions with phages using microfluidics devices that allow monitoring individual cell behaviors. Individual cell analyses provide a much more accurate image of cell physiology than population mehods. With help from Chemistry colleagues Tom Cole, Doug Grotjahn, and Byron Purse, and in collaboration with the optics expertise of Matt Anderson and the future Biophysicist, Anca Segall uses chemical fluorescent probes to investigate the function of unknown virally-encoded genes by analyzing their effect on host cell metabolism.

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Nicholas Shikuma, Mechanisms of phage-bacterium-animal interactions (Biology Department)

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Microbes are extremely important to the development and health of diverse animals. Our understanding of how microbes interact with their hosts is only in its infancy. Nick Shikuma studies microbial mediated animal development. While many bottom-dwelling marine animal populations are established and maintained by free-swimming larvae that recognize cues from surface-bound bacteria to settle and metamorphose. Nick discovered that ordered arrays of phage tail-like structures produced by a marine bacterium induce the metamorphosis of a marine tubeworm. His findings begin to explain the long-standing observation that marine biofilms trigger the metamorphosis of benthic animals andexpand the known diversity of structures and functions of phage-like particles. Nick’s laboratory applies genetic, genomic, biochemical- and cell-biology approaches to study the interactions between model bacteria and animals.

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Manal Swairjo, Structural biology of tRNA modification (Chemistry and Biochemistry Department)

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The coding properties of transfer-RNA reside in part in the post-transcriptional modifications of nucleosides in its anticodon stem-loop (ASL). These modifications fine tune gene expression by enhancing cognate and wobble codon recognition, and control ribosomal frameshifting and translocation. Manal combines biochemistry, X-ray crystallography and bioinformatics to elucidate the biosynthesis pathways to modified nucleosides of tRNA and identify new drug targets in these pathways. Her current focus is on structural and mechanistic investigations of the biosynthesis enzymes for queuosine and threonylcarbamoyl adenosine, two ASL modifications implicated in bacterial virulence and retroviral replication, respectively. These studies lay the experimental foundation for future discovery of novel antibacterial and antiviral agents by structure-based design.

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Roland Wolkowicz, Exploring viral-host interactions and gene function (Biology Department)

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Roland Wolkowicz studies viral-host interactions with the ultimate goal of blocking infection. His laboratory develops tools for the study of viral pathogenesis and the search for antiviral factors. These tools include the construction of cDNA and random peptide libraries, which are expressed in the cell utilizing retroviral technology. His technologies allow him to express any viral protein of interest in mammalian cells targeted to different cellular compartments. The laboratory extensively uses Fluorescence Activated Cell Sorting (FACS) to perform high through-put biological screens and analysis at the single cell level, complemented with microscopy analysis. Roland Wolkowicz is the Director of the SDSU Flow Cytometry Core facility. His assays, aimed at studying viral protein enzymes and the discovery of antivirals, prompted critical collaborations with Torrey Pines Institute of Molecular Studies in La Jolla and the Memorial Sloan Kettering

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