Weekly: ILC 118 – 1:30 pm to 2:20 pm
Friday, April 27, 2018
Micah Buckmiller, Ferguson Lab, Department of Physics, Boise State University
Title: “A Study of Transcriptional Activation by the Transcription Factor Gal4 in Saccharomyces cerevisiae by 3D Orbital Tracking and in vivo RNA labelling”
Deciphering stochastic biomolecular processes is crucial for our understanding of gene transcription and the intricacies of cellular metabolism. With 3D orbital tracking, we are able to visualize and monitor pre-mRNA and transcription factors in real-time using fluorescent tagging within yeast cells at a high sampling rate. Our study demonstrates that we can track these molecules of interest, fluorescent-labeled GFP (pre-mRNA) and JF 646 dye (transcription factors), during the process of transcribing a gene that codes for metabolizing galactose. This method allows us to directly observe the movement of a single molecule and determine the time lag between the GAL4 transcription factor binding to DNA and the activation of the mRNA synthesis. The data we collected improves our knowledge of the details of transcriptional kinetics and how single celled eukaryotic organisms regulate transcription. This will expand our research on the transcription processes in similar genes and in multicellular organisms like humans. 3D orbital tracking opens up a new window for exploring fundamental biochemical processes through a dynamic view of single fluorescent molecules in living systems at high speed.
Alex Sessa, Brown Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Thiolate exchange in [(L)ZnSR’]+ complexes and its relevance to the mechanism of thiolate alkylation reactions in Ada DNA repair protein.”
There is an interest to understand the mechanism of zinc thiolate alkylations because of its relevance to Ada DNA repair protein, which is a protein in E. coli that repairs damaged DNA caused by methylation. It is hypothesized that the mechanism of the enzyme follows a dissociative pathway where a zinc-bound thiolate dissociates from the zinc center and it is the free thiolate and not the zinc-bound thiolate which then abstracts the methyl group from the methylated DNA. In this experiment a series of crossover experiments using 1H NMR spectroscopy between [(L)ZnSPh-X]+ derivatives, where L = tris(2-pyridylmethyl)amine (TPA) or bispyridin-2-ylmethyl-thiophene-2-methylamine (ThDPA) and X = H, Me or NO2, provide support that thiolate dissociation is rapid in some instances but slow in others.
Friday, April 20, 2018
Kimberly Campbell, Cornell Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Novel Anthracycline Analogs for Breast Cancer Treatment: In Vitro Cytotoxicity and Fluorescence Microscopy”
Anthracyclines are one of the most effective treatments in cancers even though the side effects are very serious. Doxorubicin (DOX) is used to treat numerous cancers such as neuroblastoma, sarcoma, breast carcinoma, acute leukemia and lymphoma, etc. DOX is known to cause a dose-dependent cardiotoxicity that leads to congestive heart failure. We examined two synthetic DOX analogs (GPX-150 and GPX-160) developed to reduce cardiotoxicity for their ability to exert in vitro anticancer activity against breast cancer cell lines. The antiproliferative activity of the DOX analogs against MDA-MB-231-luc and MCF-7-luc breast cancer cells was examined using a resazurin reduction assay. The analog GPX-160 was shown to be as cytotoxic as DOX against both DOX-sensitive and DOX-resistant cell lines, and more potent than GPX-150. Fluorescence microscopy using an EVOS microscope and differential live/dead cell staining with calcein AM and ethidium homodimer-1 was also used to visualize the cytotoxic effect of the drugs on both breast cancer cell lines.
Jordan Orien, King Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Crystallization and Phase Transitions of Pharmecutical Polymorphs”
Computational chemistry is a leading field in the classification and understanding of crystal structure formation. Solid-state density functional theory (DFT) is a computational model that can be used to calculate electronic structure and properties of molecular solids. A significant breakthrough with DFT came when correction terms for van der Waals forces were incorporated into the formulation, allowing for a more accurate representation of molecular crystal structures and energies. In this study, DFT calculations are compared with terahertz spectroscopic measurements of real crystal samples of probucol, a pharmaceutical used for the treatment of high cholesterol, to study polymorphism and transitions between crystal phases. Probucol exhibits polymorphism with two possible crystal formations. The Form I crystal has a lower energy structure when crystallized from ethanol, while Form II occurs during a slow evaporation in methanol. Form II will eventually undergo a phase transition to Form I under ambient storage conditions. This is shown experimentally, but the mechanism of formation for the solvent-dependent thermodynamically favored Form II was unknown. Our results show that the incorporation of solvent molecules in crystal voids of the Form II polymorph during crystallization results in a more energetically favorable conformation. Eventual loss of methanol molecules from the crystal lattice results in a meta-stable structure that subsequently converts to the more stable Form I polymorph.
Friday, April 13, 2018
Creed Feigt, Brown Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “The Influence of Primary Coordination Sphere Effects on the Reactivity of Zinc-Thiolate Complexes”
Analogues of the Ada repair protein have been synthesized. Research has been suggested that increasing the sulfur content of the primary coordination sphere may lead to increased reactivity of the zinc complexes upon alkylation with methyl iodide. Two analogues were synthesized by replacing one of the pyridine groups in a previously synthesized nitrogen rich zinc complex [(TPA)ZnSPh]+ with one [SN2-Zn-SPh]+ and then two, [S2N-Zn-SPh]+ thiophene groups increasing the presence of sulfur in the primary coordination sphere. Alkylation of the zinc complexes showed the [SN2-Zn-SPh]+ having a larger rate constant (2.82 x 10-3 s-1) compared to [S2N-Zn-SPh]+ (8.72 x 10-4 s-1). The larger rate constant and the broadening of the thiolate peaks on 1H NMR may be evidence of increased dissociation of the Zn-Thiolate bond.
Matt Lawson, Russell Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Thermodynamics and Kinetics of the Electrochemical Reduction of Uranium”
This research seeks to stabilize nuclear waste by first characterizing uranium in a simulated “nuclear waste” environment. Hydrodynamic voltammetry via rotating disc electrode was utilized to reduce uranium from +6 to +3 oxidation state and determine the diffusion coefficient. The diffusion coefficient was observed to decrease as angular velocity increased for 100 mV/s scan rates but maintain a steady value of 4.5×10-6 ± 0.01×10-6 cm2/s through a range of 80 rpm – 150 rpm at a scan rate of 10 mV/s.
Friday, April 6, 2018
Christopher Gale, Ausman Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Investigating Known Dispersants of Single Walled Carbon Nanotubes using “Bucky Paper” Thin Films”
Single walled carbon nanotubes (SWNT) are of interest to a seemingly endless number of fields and industries. However, their use is complicated by the difficulty of dispersing the tubes and maintaining the tube’s dispersion during processing. While several dispersants have become well known for their efficacy in the literature, the details of how and why these dispersants work is unknown. We are attempting to investigate these details using carbon nanotube thin films, colloquially known as “Bucky paper”, as a useful substrate. Several Bucky paper synthesis methods were used, differing in the dispersant used before deposition onto a filter. Sodium dodecyl sulfate (SDS), sodium dodecylbenzene sulfonate (SDBS), and Triton X-100 were used. SEM was used to confirm the strong attraction expected between SWNT and and SDBS, as evidenced by structures that appear to be clumps of residual surfactant. TGA in both an inert and oxidizing atmosphere at a ramp of 10 °C/min up to a maximum of 500 °C showed no significant change in mass. This could be indicative of either a lack of residual dispersant in the Bucky paper or an exceptionally strong interaction between residual dispersant and the Bucky paper. Transmission IR and Raman spectra are being collected of the Bucky paper samples. The initial findings show the signature of the dispersant used present in IR, but this signature is not seen in Raman when excited at 633 nm. Further study hopes to identify peak shifts that might result from association with the unique electronic environment of the tube surface.
Friday, March 23, 2018
Tristan Olsen, Ausman Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Methods Towards Improving Young’ Modulus and Tensile Strength in Nanotube/epoxy Composites”
The hypothesis tested is that by ensuring that single-walled carbon nanotubes (SWNTs) are monodisperse in SWNT/epoxy nanocomposites, the mechanical properties of SWNT/epoxy nanocomposites can be significantly improved over prior literature reports. Solvent based dispersal techniques using either N,N-dimethylformamide (DMF) or N-methyl-2-pyrrolidone (NMP) were combined with high-shear mixing to make nanocomposites. Fluorescence measurements of resulting nanocomposites indicate samples prepared with NMP had more monodisperse nanotubes present. Tensile testing of nanocomposites indicate decreases in tensile strength and flexural modulus of samples with weight loadings of 0.001% SWNTs using both NMP and DMF methods.
Jason Rosecast, Brown Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “NMR Evidence for a Dissociative Pathway in the Methylation of the Ada Repair Metalloprotein Active Site”
Friday, March 16, 2018
Heather Black, Charlier Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Fluorometric Investigation into the Role of Methionine 234 in the Coenzyme Binding Site of Human Carbonyl Reductase”
Hannah Davis, Callahan Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Making Sense of Messy Meteorite Mass Spectra”
Friday, March 9, 2018
Christopher Bonner, Lee Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Colorimetric Detection of DNA via Catalytic Release of Polymer Bead-Immobilized Gold Nanoparticles”
Gold nanoparticles exhibit unique colorimetric properties due to plasmonic coupling that make them an ideal material for sensitive colorimetric sensors. DNA reaction networks have been incorporated with gold nanoparticles to produce an aggregation based detection mechanism for DNA.1 Aggregation based mechanisms, however, suffer from fundamental sensitivity limits and relatively slow kinetics. A sensor based on the disassembly of particles can overcome these limits, since the optical signal is obtained from free particles and the diffusion of free DNA is faster than that of nanoparticle-bound DNA.2
The catalytic disassembly of nanoparticles is driven by an autocatalytic network developed by Zhang et al.3 As illustrated in Figure 1, the substrate complexes of the network act as a link between gold nanoparticles and polymer microbeads. In the presence of catalyst and fuel, the substrate dissociates into waste and output, which causes a change in solution color. The substrate, nanoparticle coated beads, was assembled first to control the size and shape of gold nanoparticle aggregates. Preliminary results indicate a DNA target as low as 1 nM could be detected using the sensing mechanism.
To improve the sensitivity of the mechanism, the effect of surface DNA strands, nanoparticle and microbead sizes, and ionic strength will be investigated. The effect and reduction of leak in the system will also be explored using mismatched fuel strands4 to further increase sensitivity.
Acknowledgments: This project was supported in part by the: (1) National Science Foundation (CBET, 1706065), (2) NIH Grant No. P20 GM103408 from the Idaho INBRE Program, (3) American Chemical Society Project SEED, and (4) Boise State University.
(1) Huttanus, H. M.; Graugnard, E.; Yurke, B.; Knowlton, W. B.; Kuang, W.; Hughes, W. L.; Lee, J. Biosens. Bioelectron. 2013, 50, 382.
(2) Oishi, M.; Sugiyama, S. Small 2017, 12, 5153-5158
(3) Zhang, D. Y.; Turberfield, A. J.; Yurke, B.; Winfree, E. Science 2007, 318, 1121.
(4) Olson, X.; Kotani, S.; Padilla, J. E.; Hallstrom, N.; Goltry, S.; Lee, J.; Yurke, B.; Hughes, W. L.; Graugnard, E. ACS Synth. Biol. 2017, 6, 84.2
Ibrahem Hassan, Warner Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Synthesis of Heterocyclic Compounds through the Oxazolium Salt/Azomethine Yilde [3+2] Cycloaddition Sequence”
The azomethine yilde is a reactive intermediate often used in cycloaddition reactions with activated alkenes and alkynes (dipolarophiles) to form nitrogen-containing heterocycles, which are very important in the pharmaceutical industry. So, the study of azomethine yilde generation and its subsequent use in cycloaddition reactions continues to be important. In this project, I am inspecting the intermolecular cycloaddition reaction where the azomethine yilde is tethered to the alkene or alkyne dipolarophile through a small chain of carbon atoms. The azomethine yilde is generated from an oxazolium salt where the dipolarophile is connected at either 2, 3, or 5 position on the ring (prior work shows the sequence fails when connected at position 4). The synthesis starts from commercially available 1,5-pentanediol that produces an oxazole intermediate over five steps that include mono-protection of the diol, oxidation of the remaining alcohol to a carboxylic acid, amide formation, and then oxazole formation. The oxazole was converted to the cycloaddition precursor after three additional steps. Finally, the azomethine yilde was formed with the dipolarophile tethered at position 2. In my presentation, these and additional details about the synthesis procedure and data will be discussed.
Friday, March 2, 2018
Areli Castro, Callahan Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Developing an Analytical Method for Ancient Wine in Archaeological Samples”
Christina Lee, Cornell Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Novel Bisbenzimidazole Inhibitors of Bacterial MTN”
Friday, February 23, 2018
Kynna Bertagnolli, Cornell Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Proteomic Analysis of MTN Deficiency in Enterohemorrhagic E. coli O157:H7”
The bacterial enzyme 5’-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTN) is essential for the production of autoinducers, and required to salvage methionine and purine constituents from S-adenosyl-methionine (SAM) dependent reactions. MTN represents a potentially valuable target for the development of novel antibiotics that would attenuate virulence by interrupting quorum sensing and decreasing metabolic fitness. To further study the impact of MTN activity on cellular processes, the proteomic profiles of enterohemorrhagic E. coli (EHEC) strain O157:H7 wild type (WT) and MTN knock-out (KO) cells were analyzed using shot-gun proteomic approach following peptide labeling and liquid chromatography-tandem mass spectrometry. The results indicate that loss of MTN activity causes numerous changes in the expression of metabolic proteins. The MTN KO strain showed altered expression levels of enzymes responsible for methionine biosynthesis, spermidine biosynthesis, and radical SAM reactions that lead to the synthesis of vitamins (thiamine, lipoate, biotin). The decrease in vitamin synthesis may explain the decreases in activity of pathways involved in energy metabolism in the KO strain. Ultimately, the results suggest that antibiotics targeting MTN activity may function by widespread metabolic interruption. The impact of an MTN KO on the regulation of SAM-dependent methyltransferases, additional radical SAM enzyme activity, and polyamine dependent cellular activities will be explored in future research.
Vannessa Campfield, McDougal Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Isolation, Purification and Characterization of Novel Steroidal Alkaloids from Veratrum californicum”
Cyclopamine and other steroidal alkaloids found in Veratrum californicum are known teratogens which inhibit the Sonic hedgehog (Shh) signaling pathway. In over 20 types of cancer, this pathway is active; allowing the overproduction of cancerous cells and tumor growth. Currently, there are only a small number of medications derived from cyclopamine which serve to inhibit the pathway, thus inhibiting tumor growth in skin and neck cancers. Further examination and analysis of alkaloid extractions has confirmed various abundancies of cyclopamine and other alkaloids in different sections of the Veratrum californicum plant; with the highest cyclopamine abundancy residing in the root and rhizome section. Through the use of Shh Light II cells, bioactivity is suppressed the greatest by the root and rhizome extracts compared to bioactivities of the stem or leaf portions of the plant. Careful analysis of the root and rhizome extract by High Pressure Liquid Chromatography and MS has verified the presence of uncharacterized, novel compounds. This project concentrates on extracting, isolating and characterizing these novel compounds and other alkaloids present in the root and rhizome section of Veratrum californicum. Bioactivity of this pathway will also be tested for any synergistic effects caused by numerous combinations of novel compounds with cyclopamine that inhibits the Shh signaling pathway.
Friday, February 16, 2018
Andy Hansen, Colson Lab, Department of Chemistry and Biochemistry, Boise State University
Title: “Non-Classical Cluster Synthesis: Isocyanide-Facilitated Chain Extension of Fe2(µ-PPh2)2(CO)6 Complexes”
Transition metal carbonyl clusters (MCC’s) have been studied for decades as potential catalytic materials or as functional components in molecular electronics. Synthetic methods for producing MCC’s have historically focused on so-called “classical” clusters containing at least three transition metal nuclei participating in extensive metal-metal bonding networks. We are interested in exploring the synthesis and characterization of polynuclear transition metal complexes having non-classical architectures. An approach to synthesizing a new, multinuclear organometallic iron phosphide cluster via simple molecular precursors has been developed. The synthesis and structural characterization of a chain extended dimer based on the dinuclear Fe2(µ-PPh2)2(CO)6 complex will be presented.
Friday, February 9, 2018
Melissa Roberts, Graduate Student, Department of Chemistry and Biochemistry, Boise State University
Title: “Hot to Trot: Determination of the Organic Composition of Thermally Altered Meteorites”
It is widely believed that organic compounds were delivered to the early (and prebiotic) Earth via extraterrestrial materials such as meteorites. This research is designed to investigate several thermally altered carbonaceous chondrites and ureilites for soluble organic compounds including nitrogen heterocycles and aliphatic and aromatic hydrocarbons. Recent experimental work suggested that Fischer Tropsch-type (FTT) synthesis may have been responsible for amino acids detected in thermally altered carbonaceous chondrites and ureilites. In addition, both n-alkanes and polycyclic aromatic hydrocarbons (PAHs) should be synthesized from FTT synthesis and they should be detectable (if amino acids can survive these conditions). Furthermore, recent theoretical work determined that FTT synthesis should be the dominant source of nucleobases within model planetesimals. Thus, these compounds can serve as indicators of FTT synthesis. In addition, isoprenoid hydrocarbons such as pristine and phytane can serve as indicators of terrestrial contamination, which can help gauge the level of terrestrial contamination of these Antarctic-recovered meteorites. If nucleobases are present in thermally altered meteorites, then they will provide evidence of how common these species are in extraterrestrial material and whether they can survive harsh conditions of thermal metamorphism. This research will help answer fundamental questions regarding the diversity and abundance of organic compounds and their likely origin in in extraterrestrial small bodies.
Patrick Schwartz, Graduate Student, Department of Chemistry and Biochemistry, Boise State University
Title: “A Piece of the Cosmic Puzzle: Correlation Between Reflectance IR and Organic Abundance & Distribution”
Friday, February 2, 2018
Savannah Irving, Graduate Student, Department of Chemistry and Biochemistry, Boise State University
Title: “The Development of Continuous Head-to-Tail Depolymerizable Polymers”
Ben Lew, Graduate Student, Department of Chemistry and Biochemistry, Boise State University
Title: “Spectroscopic and Electrochemical Investigations of Tethered Organometallic Cluster Electrophores”
Friday, January 26, 2018
Dr. Lisa Warner, Assistant Research Professor, Biomolecular Research Center, Boise State University
Title: “From the periplasmic space to the extracellular matrix: Using NMR to investigate the structure and
dynamics of biomolecules.”
Warner, L.R., Gatzeva-Topalova, P.Z., Doerner, P.A., Pardi, A., Sousa, M.C. (2017) Flexibility in the Periplasmic Domain of BamA Is Important for Function. Structure 25, 94–106.
Voith von Voithenberg, L., Sanchez, C., Kang, H-S., Madl, T., Zanier, K., Bart, A., Warner, L.R., Sattler, M., Lamb, D.C. (2016) “Recognition of the 3’splice site RNA by the U2AF heterodimer involves a dynamic population shift” PNAS, 113, E7169–E7175.
Friday, January 19, 2018
Eric Bastian, Dairy West
Title: “Dairy Industry in Idaho: Potential For Chemistry Majors”
Eric D. Bastian was born in central Utah and reared on a dairy farm. He obtained his education at Utah State University with a BS degree in Dairy Science, and MS and Ph. D. (1989) degrees in Nutrition and Food Sciences. He spent one year (1989-1990) as a research fellow with the Danish Government Research Institute for the Dairy Industry in Hillerod, Denmark.
In 1992, Eric accepted a faculty position at the University of Minnesota in the Department of Food Science and Nutrition and for six years he led a research team focused on milk protein and enzyme chemistry, process cheese functionality, and milk protein fractionation. In 1998, he was promoted to Associate Professor with tenure. In the same year, he accepted a position with Avonmore West (now Glanbia) as Director of Research & Development (R&D) and relocated to Twin Falls, Idaho.
Eric was promoted to Vice President of R & D for Glanbia Nutritionals in 2006 and he began leading the cheese R&D for Glanbia Foods in 2013 (both divisions were part of Glanbia PLC). In 2015, Eric was promoted to Senior Vice President of Innovation. During his time at Glanbia Nutritionals, he developed a research team, starting with 5 people and building to a team of 80.
In July of 2016, Eric joined Dairy West as Vice President of Industry Relations.
Eric is married with five children and lives in Twin Falls, Idaho. He enjoys many outdoor activities including snow and water skiing, gardening, camping and fishing. He also likes to read historical and classical literature.