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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.