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Affiliation:

Research:

Abstract: Recent efforts by our group and others have shown the promise of applying single molecule methods to link mechanistic detail about protein adsorption to macroscale observables. When we study one molecule at a time, we eliminate ensemble averaging, thereby accessing underlying heterogeneity. However, we must develop new methods to increase information content in the resulting low density and low signal-to-noise data and to improve space and time resolution. 

I will highlight recent advances in super-resolution microscopy for quantifying the physics and chemistry that occur between target proteins and stationary phase supports during chromatographic separations. My discussion will concentrate on the newfound ability of super-resolved single protein spectroscopy to inform theoretical parameters via quantification of adsorption-desorption dynamics, protein unfolding, and nano-confined transport. Additionally, I will discuss using phase manipulation to encode temporal and 3D spatial information, and the opportunities and challenges associated with such imaging methods.

Abstract:  Conventionally physical chemistry is a field that mainly investigates physicochemical phenomena at atomic and molecular levels. Noticing the analogy between molecular (especially macromolecular) dynamics and cellular dynamics, in the past few years my lab has focused on introducing and generalizin

g the techniques and concepts of physical chemistry into cell biology studies. In this talk I will first discuss a long-standing Nobel-Prize winning puzzle on olfaction. Each olfactory sensory neuron stochastically expresses one and only one type of olfactory receptors, but the molecular mechanism remained unanswered for decades. I will show how simple physics taught in introductory physical chemistry textbook explains this seemingly complex problem, and briefly mention our ongoing efforts of investigating chromosome dynamics with a CRISPR-dCas9-based live cell imaging platform. 

In the second part of my talk, I will discuss our efforts on developing an emerging new field of single cell studies of the dynamics of cell phenotypic transition (CPT) processes, in parallel to single molecule studies in  chemistry. Mammalian cells assume different phenotypes that can have drastically different morphology and gene expression patterns, and can change between distinct phenotypes when subject to specific stimulation and microenvironment. Some examples include stem cell differentiation, induced reprogramming (e.g., iPSC) and others. In many aspects a CPT process is analogous to a chemical reaction. Using the epithelial-to-mesenchymal transition as a model system, I will present an integrated experimental-computational platform, and introduce concepts from chemical rate theories such as transition state, transition path, and reactive/nonreactive trajectories to quantitatively study the dynamcis of CPT processes.

Research:

Abstract: The neoclerodane diterpene salvinorin A is the major active component of the hallucinogenic mint plant Salvia divinorum Epling & Játiva (Lamiaceae), a plant recently scheduled in many countries. Salvinorin A is a potent k opioid receptor agonist and atypical dissociative hallucinogen. However, it has also emerged as a valuable tool for gaining additional insight into the pharmacology of opioid receptors. This presentation will highlight our previous and ongoing efforts to understand the chemistry and biology of salvinorin A and related neoclerodanes at opioid receptors. In particular, we will describe our chemical strategy to deliberately simplify and introduce functionality about the target molecule to provide access to molecular features on salvinorin A otherwise unattainable by semisynthesis.

Research:

Abstract: Dinoflagellates are an important group of eukaryotic microorganisms found in freshwater and marine environments. Certain dinoflagellates produce potent toxins that are the causative agents of diarrheic, amnesic, paralytic, and neurotoxic shellfish poisonings, and are responsible for the formation of harmful algal blooms (red tides). Still other dinoflagellates are capable of both photosynthesis and bioluminescence, processes that are regulated by a cellular circadian rhythm (biological clock) and give rise to bioluminescent bays and the ‘phosphorescence’ of the sea. The key, light-forming enzyme of dinoflagellate bioluminescence, dinoflagellate luciferase (LCF), contains three homologous catalytic domains within a single polypeptide and is tightly regulated by pH. The production of blue-green light by LCF is coupled to the oxidation of an open-chain tetrapyrrolic substrate, dinoflagellate luciferin (LH2), which is a catabolite of the photosynthetic pigment chlorophyll. Current progress in our understanding of LH2 biosynthesis and the chemiluminescent and pH-dependent activation mechanisms of LCF will be presented.

Research:

Abstract: The (4+3)-cycloaddition reaction is a quick and efficient entry to seven-membered rings, and those that are larger and smaller as well.  This presentation will focus on our contributions to this area from both a historical and present-day perspective.  This latter aspect will be dominated by our work on the cycloaddition reactions of oxidopyridinium ions.

Research:

Michael Harmata was born in Chicago in 1959.  He attended St. Michael the Archangel grammar school, Thomas Kelly High School, and the University of Illinois-Chicago, where he received his AB degree in chemistry with a math minor in 1980, working in the labs of Jacques Kagan and graduating with honors and highest distinction and all that great stuff that doesn’t matter anymore.  He earned his PhD under the tutelage of Scott E. Denmark at the University of Illinois in Urbana, Illinois in early 1985, working on carbanion-accelerated Claisen rearrangements.  He then did an NIH postdoc with Paul A. Wender at Stanford University where he performed some of the first work on the synthesis of the neocarzinostatin chromophore.  He began his independent career at the University of Missouri-Columbia in 1986, where he is now the Norman Rabjohn Distinguished Professor of ÌÇÐÄvlog¹Ù·½Èë¿Ú.  He has been contributed significantly to the areas of (4+3)-cycloaddition reactions, benzothiazine chemistry, pericyclic reactions of cyclopentadienones, chiral molecular tweezers, silver-catalyzed chemistry, and more.

Abstract: Proteostasis deficiency in ion channels leads to a variety of ion channel diseases called channelopathies, which are often caused by excessive endoplasmic reticulum-associated degradation (ERAD) and inefficient membrane trafficking of mutant ion channels. We focus on proteostasis maintenance of gamma-aminobutyric acid type A (GABA_A) receptors, the primary inhibitory ion channels in the mammalian central nervous system. Numerous epilepsy-associated missense mutations in the receptor subunits predispose them to rapid ERAD, reduce their cell surface expression, and cause loss of their function. We aimed to use small molecules to adapt the proteostasis network in the ER to restore the surface trafficking and function of such mutant receptors. Our screening assay from a structurally diverse FDA-approved drug library identified lead compounds that enhanced the surface expression of a number of trafficking-deficient mutant receptors. Furthermore, patch clamping electrophysiology showed that these lead compounds restored their function on the plasma membrane. Mechanistic studies revealed that they reduced the degradation by attenuating the ERAD pathway. In addition, they enhanced the folding of the mutant subunits by enhancing their interactions with major GABAA receptors-interacting chaperones. Both ERAD inhibition and folding enhancement contributed to the improved ER-to-Golgi trafficking efficiency of the mutant receptors. These compounds hold the promise to be further developed to ameliorate idiopathic epilepsy resulting from excessive GABA_A receptor degradation.

Research:

Bio: David Mitzi is the Simon Family Professor at Duke University, with appointments to the Departments of Mechanical Engineering and Materials Science and ÌÇÐÄvlog¹Ù·½Èë¿Ú. He received his B.S. in Electrical Engineering and Engineering Physics from Princeton University (1985) and his Ph.D. in Applied Physics from Stanford University (1990). Prior to joining the faculty at Duke (2014), Dr. Mitzi spent 23 years at IBM’s Watson Research Center, where his focus was on the search for and application of new electronic materials, including organic-inorganic perovskites and inorganic materials for photovoltaic, LED, transistor and memory applications. For his final five years at IBM, he served as manager for the Photovoltaic Science and Technology Department, where he initiated/managed a multi-company program to develop a low-cost, high-throughput approach to deposit thin-film chalcogenide-based absorbers for high-efficiency photovoltaics. Dr. Mitzi has recently been elected a Materials Research Society (MRS) Fellow and named a Clarivate Analytics Highly Cited Researcher.

Abstract: Although known for over a century, organic-inorganic hybrid perovskites have received extraordinary attention recently, because of unique physical properties for the three-dimensional (3-D) lead-based systems, which make them outstanding candidates for application in photovoltaic and related optoelectronic devices. This talk will highlight the outstanding chemical flexibility of the more diverse 2-D perovskite family. As part of the discussion, the importance of structural dimensionality for determining semiconducting character, along with opportunity for both inorganic/organic structural components to play an active role in determining hybrid properties, will be emphasized. In addition to structural/electronic flexibility of the 2-D perovskites, the talk will explore the unique challenges for preparing high-quality films of these systems, and will present recent progress along several fronts, including melt-processing and resonant-infrared matrix-assisted pulse laser evaporation. Outstanding functionality combined with versatile and facile processing provide two pillars for future application and study of this family.

Abstract: The RNA-binding protein La-related protein 1 (LARP1) helps regulate the synthesis of ribosomes, the cellular machines that translate messenger RNAs (mRNAs) into proteins. Ribosomes themselves include many protein subcomponents that are critical for their functioning. The mRNAs that encode these ribosomal subcomponents, called 5’TOP mRNAs, are chemically distinct from most other mRNA molecules. LARP1 binds 5’TOP mRNAs, thereby controlling to what extent they are available for ribosome biosynthesis. Molecular dynamics simulations of LARP1 reveal that a portion of the protein near the 5’TOP-mRNA binding site is particularly flexible. Elevated LARP1 levels have been implicated in several cancers, so better understanding LARP1 dynamics could provide pharmacological insights that will lead to novel treatments.

Research:

Abstract: In an energy landscape with increased environmental concerns and reduced availability of fossil fuels, electrochemical systems will likely play a major role for automotive and grid-storage applications.  Our research strives to diagnose and overcome challenges related to electrochemical energy storage. We focus on mechanistic analysis that integrates both theory and experiment.  In this talk, I will discuss three applications of the aforementioned research approach ranging from the molecular to the device scale. In the first, we consider the origin of pH-dependent kinetics for hydrogen evolution and oxidation. Using single-crystal voltammetry and microkinetic modeling, we find that adsorbed hydroxide is a spectator at best and a poison at worst. The implications of this finding on electrocatalyst design are discussed. In the second application, we investigate the effect of inter-electrode communication on failure mechanisms in Li-ion batteries. Electrochemical characterization of surface films using redox mediators separates transport and kinetics to determine how nominally passivating films can selectively transfer charge. These results highlight the importance of a defect-free inorganic layer for a successful interface. Finally, we apply our approach to battery electrode design. We combine rheology with electrochemical analysis to determine the role of carbon microstructure in battery performance and reach the counter-intuitive conclusion that short-range electron transport is more limiting than either long-range conductivity or tortuous ion paths.

Maureen Tang joined the faculty of Chemical and Biological Engineering at Drexel University in fall 2014. She received her BS in Chemical Engineering from Carnegie Mellon University in 2007 and her PhD from the University of California, Berkeley in 2012. While at Berkeley, she received a NSF Graduate Research Fellowship, an NSF East Asia Pacific Summer Fellowship, and the Daniel Cubiciotti Student Award of the Electrochemical Society. Dr. Tang completed postdoctoral work at Stanford University and research internships at Kyoto University, the University of Dortmund, and DuPont. She is the recipient of a 2018 NSF CAREER award, the 2019 College of Engineering Early Career Research Award, and a 2018 Award for Excellence in Peer Review from the ACS PRF. Her research at Drexel develops materials, architectures and fundamental insight for electrochemical energy storage and conversion.