Analytical, Physical and ChemBio Seminar
Wednesday, February 1, 3:30 - 4:30pm, WEL 2.122
University of Utah
Abstract: In the last 5 years, there have been extensive studies and new materials designed for interfacing biocatalysts with electrode surfaces for applications in sensing, energy storage and electrification of industry. This talk will discuss electroanalytical techniques for studying biocatalysis, including both mediated enzymatic bioelectrocatalysis and direct enzymatic bioelectrocatalysis. The talk will discuss electrode materials innovation for interfacing complex proteins with electrode surfaces for facile electron transport as well as using them for electrosynthesis of ammonia as well as other value-added products (i.e. chiral amines, chiral imines, polymers, etc.) with a focus on sustainability. Finally, this talk will discuss the use of synthetic biology for microbial bioelectrosynthesis of ammonia and other value-added products, as an alternative to enzymatic bioelectrocatalysis.
Analytical, Physical and ChemBio Seminar
Thursday, February 2, 3:30 - 4:30pm, WEL 2.122
Abstract: The plasma membrane is a complex boundary between the cell and its surroundings. Cells have an array of protein receptors on the plasma membrane that help process environmental cues. The spatial and temporal arrangement of these receptors is critical to function, but the chemical forces driving this organization are not well understood. In my lab, we develop and apply a variety of fluorescence assays to measure membrane protein interactions in situ. This talk will focus on receptor tyrosine kinases (RTKs), which are transmembrane proteins that regulate cell growth, proliferation, and differentiation. Several RTKs are oncogenic and are targeted in next generation anti-cancer drug development. My lab has resolved functionally important interfaces in RTKs using pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS is especially powerful because it is sensitive to protein mobility, concentration, and monomer/dimer/oligomer distributions. I will describe ongoing work in my group to investigate two RTKS: EGFR and EphA2.
Analytical, Physical and ChemBio Seminar
Thursday, February 9, 3:30 - 4:30pm, WEL 2.122
Johns Hopkins University - School of Medicine
Abstract: The ability to continuously monitor fluctuating concentrations of specific molecules in the body can drastically improve precision medicine by allowing the real-time correlation of dynamic molecular processes with health and disease. While this ability has been pursued from multiple directions, electrochemical strategies have been successful and commercializable platforms. For example, continuous glucose monitors have dramatically improved the therapeutic management and quality of life for Type 1 diabetics. Unfortunately, the enzymatic sensing used in glucose monitors is not applicable to a large number of clinically relevant biomarkers. This limitation significantly reduces the scope of dynamic biochemical processes we can probe to study healthy human physiology and disease. In response, my laboratory is developing in vivo electrochemical aptamer-based sensors, a platform that is generalizable to the highly specific sensing of arbitrary molecular targets and supports continuous molecular monitoring in the body. In this presentation I will discuss the current state-of-the-art of these sensors, and the challenges we are addressing to enable preclinical and clinical applications.
Inorganic / ChemBio Seminar
Wednesday, February 8, 3:30 - 4:30pm, WEL 2.122
University of Illinois Urbana Champaign
Abstract: Reactions catalyzed by metalloenzymes underpin global geo- and biochemical cycles, biological energy conversion, transport, and biosynthetic processes of fundamental import to human and global health. The vast majority of these reactions follow a mechanistic paradigm in which rate-limiting conformational changes precede chemistry. This pattern suggests that such conformational gating mechanisms may be important in maintaining fidelity, control, and energy efficiency during thermodynamically and kinetically challenging transformations. To test this hypothesis, my lab is preparing and examining synthetic and artificial systems to serve as simplified models of conformationally gated control over metal ion reactivity. Using light to drive changes in ligand conformation, we exert control over the kinetics of electron transfer in synthetic copper coordination complexes. Using allosteric binding events to drive changes in protein macrostructure, we exert control over metallocofactor microenvironment in artificial metalloproteins. Finally, we use proton-coupled electron transfer to drive carboxylate shift reactions in biomimetic dinuclear cobalt complexes. All of these works are unified by the goal of (a) quantitating the kinetic and thermodynamic impact of conformational control, and (b) leveraging this impact in applications ranging from solar energy conversion, to biomedical imaging, and catalyst design.
Organic / ChemBio Seminar
Friday, February 10, 3:30 - 4:30pm, WEL 2.122
Abstract: By virtue of their unrivaled selectivity profiles, enzymes possess remarkable potential to address unsolved challenges in chemical synthesis. The realization of this potential, however, has only recently gained traction. Recent advances in enzyme engineering and genome mining have provided a powerful platform for identifying and optimizing enzymatic transformations for synthetic applications and allowed us to begin formulating novel synthetic strategies and disconnections. This talk will describe our recent efforts in developing a new design language in chemical synthesis that centers on the incorporation of biocatalytic approaches in contemporary synthetic logic. Case studies will focus on the use of this platform in the chemoenzymatic syntheses of complex natural products and also highlight how this platform could serve as a starting point to enable further biological and medicinal chemistry discoveries.
Organic Seminar: Vista Chemical Company Regents Endowed Memorial Lectureship in Organic Chemistry
Friday, May 19, 3:30 - 4:30pm, WEL 2.122
University of Pennsylvania
Abstract: Many organic reactions are mechanistically driven by two-electron processes. Although such methods are highly effective for a vast number of transformations, there are still many such conversions that have proven challenging or that suffer from harsh reaction conditions or intolerance of sensitive functional groups. The limitations of such transformations are often inherent to the mechanism of these processes at the most fundamental level, and thus predispose many of these reactions for failure. Processes transpiring via single electron mechanistic paradigms have promise to resolve some of the limitations. Described will be our efforts to develop a suite of radical precursors generated by photoredox chemistry, and the incorporation of these radicals in diverse carbon-carbon and carbon-heteroatom bond-forming transformations, emphasizing the tolerability of the developed conditions to an unprecedented array of functional groups. The value of generating radicals in a process that is synchronized and catalytic will be emphasized. Sequential transformations and multi-component reactions based on radical chemistry will be outlined, both in dual catalyzed processes and in radical/polar crossover processes where a subsequent catalytic transformation is not utilized. Applications of methods developed to DNA Encoded Library synthesis will be presented.
Analytical, Physical and ChemBio Seminar
Thursday, January 26, 3:30 - 4:30pm, WEL 2.122
Abstract: Microdroplet chemistry has received increasing attention for accelerated reactions at the air/solution interface in recent years. However, a large and significant category of reactions not demonstrated in microdroplets is the electrochemical reaction. This talk will discuss our progress toward microdroplet electrochemical strategies which include (i) a voltage-controlled interfacial microreactor that allows acceleration of electrochemical reactions for the first time; (ii) novel interfacial electrochemical reactions that address various long-standing isomeric problems in lipid isomer analysis; (iii) novel mass spectrometry screening platform that uses picomole-scale anodic corrosion of transition metal electrodes (e.g., Pd) to enable the rapid discovery of transition metal catalysis.
Welch Emerging Leaders in Chemistry Visitor Series
Wednesday, January 25, 3:30 - 4:30pm, WEL 2.122
University of British Columbia
Abstract: Carbon capture and utilization schemes require that CO2 captured from the atmosphere (or a point source) be released from the sorbent, and that the sorbent be recycled to capture additional CO2. Alkaline solutions such as KOH are effective at capturing CO2 through reactions that form (bi)carbonates, but the recovery of CO2 gas and hydroxide before CO2 electrolysis requires energy-intensive steps. We have solved this problem by designing an electrochemical reactor that converts bicarbonate “reactive carbon capture solutions” into carbon-containing products. In this presentation, I will show how this reactor couples CO2 utilization with upstream carbon capture, and also how it can perform better than the reactors fed with gaseous CO2 that are widely studied today..
Monday, January 23, 3:30 - 4:30pm, WEL 2.122
University of Florida - Scripps Biomedical
Abstract: The Natural Products Discovery Center (NPDC) at UF Scripps Biomedical Research houses one of the world’s largest Actinobacterial Strain Collections, totaling ~125,000 strains. These strains, isolated over the last eight decades and from 69 different countries, encode natural product chemical and biological diversity that are impossible to reproduce in laboratory settings today. We have launched a large-scale genome sequencing campaign to establish the Actinobacterial Genome Database at NPDC. The sequenced genomes, together with the strains, will be made available to the scientific community to enable natural product training, research, and associated applications. Lessons learned from our natural products program over the years and preliminary analysis of the strains sequenced to date, benchmarking against the sequenced genomes available in public databases, will be presented to highlight how such a community resource could radically transform the current paradigm of natural products and drug discovery.
Friday, January 13, 3:30 - 4:30pm, WEL 2.122
Washington University - St. Louis
Abstract: RNA undergoes extensive modification through enzymatic post-transcriptional editing events. Adenosine-to-inosine (A-to-I) editing is one of the most widespread and impactful of these modifications and is catalyzed by adenosine deaminases acting on RNA (ADARs). Resulting inosines base pair with cytosine, essentially re-coding adenosine sites to guanine. Editing is essential for a number of processes including embryogenesis, neurological function, and innate cellular immunity. Dysfunctional editing is also linked to auto-immune diseases, neurological disorders, and several types of cancer. Despite this importance, numerous challenges remain for studying A-to-I editing, and our overall understanding of the locations and frequency of inosine sites remains limited. To address this challenge, we have repurposed EndoV from an RNA-cleaving enzyme into an RNA-binding protein and demonstrated its use for mapping of A-to-I editing sites and global profiling of RNA inosine content in cells and tissue samples.
Wednesday, January 11, 3:30 - 4:30pm, WEL 2.122
Penn State University
Abstract: Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, high salinity, and low or high pH values. In some archaea, such as Methanocaldococcus jannaschii, these lipids are further modified by forming carbon–carbon bonds between the termini of two lipid tails within one glycerophospholipid to generate the macrocyclic archaeol or forming two carbon–carbon bonds between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). GDGT contains two 40-carbon lipid chains (biphytanyl chains) that span both leaflets of the membrane, providing enhanced stability to extreme conditions. How these specialized lipids are formed has puzzled scientists for decades. The reaction necessitates coupling two completely inert sp3-hybridized carbon centers, which has not been observed in nature. Here we use X-ray crystallography, high-resolution mass spectrometry, chemical synthesis, and biochemical analyses to show that the gene product of mj0619 from M. jannaschii, which encodes a radical S-adenosylmethionine enzyme, is responsible for biphytanyl chain formation during synthesis of both the macrocyclic archaeol and GDGT membrane lipids.
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