The Beckman Mentors: Description of Research Projects
Ball Laboratory: Metal-Catalyzed Incorporation of Sulfur Dioxide into Organic Molecules. The Ball lab is applying organometallic catalysis to develop new methodologies to incorporate environmental pollutants into organic molecules. Sulfonylated organic compounds (containing the SO2 moiety) have extensive applications from polymers to pharmaceuticals. One class of sulfonylated compounds, sulfonyl fluorides, display promise as protease inhibitors and biological probes. Additionally, these compounds may serve as synthetic precursors to other, key sulfonylated compounds. Currents project are focused on: (i) One-pot Pd-catalyzed reactions to make sulfonyl fluorides protease inhibitors, and (ii) stoichiometric mechanistic studies using model Pd-fluoride complexes to understand SO2 insertion and provide kinetic information on C–SO2–F bond formation from the Pd center.
Cavalcanti Laboratory: Computational analysis of ciliate evolution. Ciliates are unicellular eukaryotes that present nuclear dimorphism. We use computational simulations and mathematical modeling to study how this nuclear organization evolved and what are the consequences of this unique nuclear organization on the evolution, population dynamics, and aging of these organisms. A second project involves the study of fusion genes in eukaryotic genomes. We have developed software to detect fusion genes in sequenced genomes and are currently identifying and characterizing novel fusion genes in multiple genomes. Finally, my lab is involved in several microbiome projects to characterize the microbial communities in different environments, like hot springs, mud volcanoes, soils and rivers.
Crane Laboratory: Mechanisms of microbial elemental sulfur reduction at the community, cellular and enzymatic levels. Sulfur-based respiration has been proposed to be one of the earliest energy conserving pathways for life on earth, and the pathway remains important to the sulfur and other elemental cycles in oceans, the atmosphere, sediments and the deep subsurface. It is also of specific interest in petrochemical and other fields due to the extremely corrosive and toxic effect of microbially-produced sulfides. The mechanisms of microbial sulfur respiration have, however, only begun to be understood, and their contribution to sulfur cycling overall has been almost entirely overlooked. It is not at all clear which forms of sulfur contribute to this metabolism in situ or how, mechanistically, these enzymes carry out this transformation. The relative levels of sulfur-reducing enzymes and microbes in many environments remain unknown. These overarching questions will be approahced by focusing on a specific environment – a deep, hot hydrocarbon-rich reservoir – and integrate studies 1) at the level of the microbial community by characterizing the microbes in the deep, hot subsurface environment and identifying sulfur-reducing microbes and enzymes through metagenomic and metatranscriptomics, 2) at the enzymatic level by determining the mechanisms of sulfur-reducing enzymes by kinetic and structural techniques, and 3) at the geochemical level by using cyclic voltammetry to determine the chemical speciation of sulfur in situ and during reduction by microbes and enzymes. Each aspect of these studies depend on and drive each other.
Johal Laboratory: Dual Polarization Interferometry (DPI) and Quartz Crystal Microbalance (QCM-D) Analysis of Ligand-Protein Interactions at the Solid-Aqueous Interface. The underlying theme of our research program is to take advantage of molecular self-assembly processes to construct functional nano-materials for optical and biosensing applications. Our research program primarily explores the electrostatic self-assembly (ESA) of novel polyelectrolytes, biological macromolecules, and ionic surfactants using layer-by-layer (LbL) methods, including direct adsorption and spin-assembly, to fabricate well-defined multilayer assemblies. Current work focuses on characterizing protein-drug and membrane-peptide antibiotic interactions at the solid-liquid interface, by using DPI and piezoelectric gravimetric QCM-D methods.
Johnson Laboratory: Molecular mechanisms of function of Syndecan. To build a functional nervous system, neurons must extend axons and build synaptic connections. The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) regulates axon guidance at the central nervous system midline by facilitating high affinity Slit/Robo interactions. In addition, Sdc works with the phosphatase LAR to control synapse formation at the neuromuscular junction. We determine how Sdc regulates CNS development by characterizing the interaction between Sdc and other HSPGs, conducting a structure/function analysis of Sdc in vivo, identifying binding partners for the cytoplasmic domains of Sdc, and elucidating the function of genes that interact with Sdc.
Liu Laboratory: Regulatory RNAs and bacteria. We investigate small, regulatory ribonucleic acids (sRNAs) that may be involved in controlling carbon metabolism in bacteria. In particular, we use biochemical and molecular biology techniques to decipher the mechanism by which sRNAs affect gene expression in Vibrio cholerae, the causative agent of cholera. We are also interested in applying our gathered knowledge about riboregulators towards the design and construction of RNA-based sensors for small organic molecules, including intracellular secondary messengers and extracellular pollutants.
Martinez Laboratory: Biology of ageing in Hydra. We are currently studying a species of Hydra, H. oligactis, which can be induced to age by exposure to low temperatures. One remarkable outcome was the discovery that aging in H. oligactis is reversible. These ‘revertant’ animals, are somehow able to escape the aging process and live indefinitely. We have been employing next- generation sequencing technologies to study aging in Hydra. We aim to sequence the transcriptomes of revertant (immortal) and non-revertant (mortal) Hydra, to identify what genes are allowing some individuals to escape the aging process and become immortal.
Olson Laboratory: Development and Formation of Nematode Egg Shells
Our research focuses on the use of the nematode worm C. elegans, a roundworm, as a model organism to study how protective barriers form around embryos by using fluorescence microscopy, biochemistry, molecular biology and genetic approaches. Findings from this study could shed light on the early embryonic development in other species, including mammals. Another goal is to identify new drug targets to fight parasitic roundworm infection in humans, plants and animals. Parasitic worms affect people in developing countries in Africa, Central and South America and Southeast Asia. Their infections are a major burden that cause loss in agriculture, sickness in humans and loss of productivity. If we can figure out how the worm’s eggshell is built, we can also figure out how to destroy it in the parasitic worms.
Our research focuses on the use of the nematode worm C. elegans, a roundworm, as a model organism to study how protective barriers form around embryos by using fluorescence microscopy, biochemistry, molecular biology and genetic approaches. Findings from this study could shed light on the early embryonic development in other species, including mammals. Another goal is to identify new drug targets to fight parasitic roundworm infection in humans, plants and animals. Parasitic worms affect people in developing countries in Africa, Central and South America and Southeast Asia. Their infections are a major burden that cause loss in agriculture, sickness in humans and loss of productivity. If we can figure out how the worm’s eggshell is built, we can also figure out how to destroy it in the parasitic worms.
Sazinsky Laboratory: Microbial Sulfur Metabolism & Protein Engineering. Our lab utilizes protein crystallography, enzymology and recombinant DNA technologies to study and engineer enzyme function. Current efforts aim to explore the (i) the reactivity and mechanism of enzymes involved in microbial sulfur respiration and biogeochemical sulfur cycling enzymes and (ii) glycosyl hydrolases that improve the bioavailability medicinally important natural compounds by removing a rhamnose modifications. the structure and function of rhamnosidases.
Elizabeth Glater: Recognition of Natural Odor Blends and Neuronal Circuitry.
In our laboratory, we study the neuronal circuitry underlying decision-making behavior in the free-living nematode, C. elegans. Specifically, we examine the preference of C. elegans for complex food odors and how genetic background and environment modify these preferences. Although a lot is known about how C. elegans responds to different pure odors, less is known about how C. elegans recognizes and discriminates among complex mixtures of volatile chemicals released by bacteria, their major food source. Does C. elegans use a single odorant or a bouquet of odorants to distinguish among different species of bacteria? We are identifying the attractive and repulsive odorants released by bacteria found in the natural habitat of C. elegans using solid-phase microextraction gas chromatography-mass spectrometry (SPME–GC-MS) in collaboration with Charles Taylor (Chemistry Department, Pomona College). We are also examining the neural machinery underlying bacterial preference among a diverse set of bacterial species found in the natural environment of C. elegans. Although the neurons required for the detection of specific food-odors have been well-defined, less is known about the sensory circuits underlying the discrimination among the mixtures of odors released by bacteria.
In our laboratory, we study the neuronal circuitry underlying decision-making behavior in the free-living nematode, C. elegans. Specifically, we examine the preference of C. elegans for complex food odors and how genetic background and environment modify these preferences. Although a lot is known about how C. elegans responds to different pure odors, less is known about how C. elegans recognizes and discriminates among complex mixtures of volatile chemicals released by bacteria, their major food source. Does C. elegans use a single odorant or a bouquet of odorants to distinguish among different species of bacteria? We are identifying the attractive and repulsive odorants released by bacteria found in the natural habitat of C. elegans using solid-phase microextraction gas chromatography-mass spectrometry (SPME–GC-MS) in collaboration with Charles Taylor (Chemistry Department, Pomona College). We are also examining the neural machinery underlying bacterial preference among a diverse set of bacterial species found in the natural environment of C. elegans. Although the neurons required for the detection of specific food-odors have been well-defined, less is known about the sensory circuits underlying the discrimination among the mixtures of odors released by bacteria.
