Calendar
Calendar
Seminar Series: Fall 2009
All seminars are Fridays, 3-4pm in Druckenmiller 20 with a student reception in Druckenmiller 26 prior to the seminar, unless otherwise noted.
Friday, September 18, 2009
Russell Bowers '85, Associate Professor of Chemistry, University of Florida
Spin Polarization Enhancement Methods for Sensitivity Enhancement in Nuclear Magnetic Resonance
Nuclear magnetic resonance (NMR) is a versatile spectroscopic technique employed 
extensively in chemistry, biology, physics, medicine, engineering and many other fields. Acquiring an NMR spectrum normally involves two sequential steps: (1) ordering of the magnetic nuclear spins in an applied magnetic field, and (2) stimulation and detection of transitions between nuclear spin quantum states by a resonant radiofrequency electromagnetic field. NMR spectra are rich in structural and dynamical information on the atomic length-scale. However, in many cases, the applicability of NMR is limited by its inherently poor sensitivity, which stems from the unfavorable Boltzmann factor and the inefficiency of detecting radio-frequency photons. This talk will explain how couplings of nuclear spins to rotational, orbital, and electron spin degrees of freedom can be exploited to dramatically increase the sensitivity of NMR. Specifically, three different NMR sensitivity enhancement methodologies will be described: (1) parahydrogen induced nuclear polarization, (2) spin exchange optical pumping in gases and solids, (3) resistively detected nuclear magnetic resonance. Some applications which have been enabled by each of these techniques will be presented.
Friday, September 25, 2009
Jennifer Cordes Darnell '85, Research Associate Professor, Rockefeller University
Crosslinkin-IP (CLIP) identification of novel pre- and post-synaptic RNA targets of the Fragile X mental retardation protein, FMRP
Fragile X Syndrome presents with a clinical picture of moderate to severe mental retardation and behavioral abnormalities including autistic features resulting from the loss of function of an RNA-binding protein, FMRP. Though the disease is usually caused by a triplet repeat expansion in the 5'UTR of the FMR1 gene leading to loss of transcription of FMR1 mRNA, one severely affected patient has a point mutation in one of the RNA-binding domains of FMRP. We have introduced this mutation in a mouse model and phenocopied the disease, suggesting that loss of RNA binding by the second KH domain of FMRP leads to the synaptic dysfunction underlying the cognitive and behavioral deficits observed in the syndrome. Thus, identifying the RNA ligands of FMRP in neurons is of great importance to the understanding both of the disease and normal synaptic function. Identification of in vivo RNA targets for RNA-binding proteins (RBPs) has proven difficult. We have recently developed CLIP (crosslinking-immunoprecipitation) as a novel method for capturing RBPs bound to their RNA targets in living tissue (Ule et al. Science 302:1212). CLIP uses UV irradiation to penetrate tissue and create a covalent bond between proteins and bound RNA. There are two substantial advantages to this technique over previous methods. Since RBPs are covalently crosslinked to RNA ligands without lysing the tissue, the problem of artifactual reassociation of RBPs with spurious RNA ligands has been overcome. Additionally, the covalent bond between protein and RNA allows for complete dissociation of large mRNP complexes and rigorous purification of the RBP-RNA of interest, including IP and SDS-PAGE. The majority of FMRP in brain is polysome-associated. This finding, and the localization of FMRP at synapses suggests that FMRP functions to regulate the local translation of proteins at synapses in response to activity. We now apply a modification of CLIP to the study of polysome-associated FMRP ligands and have reproducibly identified a set of RNA targets that includes MAP1B, CaMK2a and PSD-95, three RNA targets of FMRP previously validated by our lab and others. In addition, we describe unexpected RNA targets of FMRP whose mistranslation in presynaptic or postsynaptic neurons may underlie the defects in synaptic plasticity seen in the disease.
Friday, October 16, 2009
Thomas Moore, Director of the Center for Bioenergy & Photosynthesis, Professor of Chemistry and Biochemistry, Arizona State University
Balancing Earth's Energy Budget - Pay Now or Pay Later
Anthropogenic climate change is a problem facing humanity that is no less significant than war, famine, disease, the plight of refugees and the guarantee of human rights across the lands. Because climate change is inextricably linked to energy production and use, our mandate is convergence of Earth's develpmentally diverse peoples to sustainability. Biological energy transduction processes offer examples of elegant machinery, made of earth-abundant materials, that operate efficiently and essentially isothermally. Moreover, biological systems exhibit repair, self-assembly and replication - features that so far remain elusive to human-engineered devices. Biological mainstream processes that might be advantageously incorporated into emerging energy technologies include catalysts for O2/H2O,H+/H2,CO2/CH2O redox reactions, reactions involving making/breaking carbon-carbon bonds, the redox chemistry of nitrogen, and many others. Focusing on solar energy conversion, photosynthesis inspires us to imagine technologies that would convert solar energy to fuel at rates commensurate with human use. Aspects of photosynthetic machinery that are important to future solar technologies include energy transfer, photoinduced electron transfer at molecular heterojunctions, protective mechanisms, and control networks. In addition to the design, synthesis and assembly of constructs that carry out such processes, artificial photosynthesis can define the design parameters to be used in the nascent filed of synthetic biology to make vast, much needed improvements in the energy yield of photosynthesis.
Thursday, October 22, 2009
Malcolm Forbes, Professor of Chemistry, University of North Carolina
Fun Facts About Triplet States: The Photochemistry of Nanocrystalline Ketones
This lecture will begin with a brief history of the organic molecular triplet state, its connection to phosphorescence, and its detection by electron paramagnetic resonance spectroscopy. Comparison of steady-state and time-resolved EPR methods will be presented, as applied to triplet states created in single crystals as well as randomly oriented frozen glasses. The main structural parameter obtained from EPR spectroscopy of triplet states is the dipolar coupling D, and anisotropic parameter related to the distance between the unpaired electrons. The spin-correlated radical pair, normally observed in confined media such as micelles or reverse micelles, can be thought of as a weakly coupled triplet state, and its major spin-spin coupling is that from the isotropic exchange interaction J between the unpaired spins. Spectra from either triplet states or correlated radical pairs are often strongly spin polarized, i.e. they exhibit non-Boltzmann spin state populations (enhanced absorption (A) and/or emission (E)). This polarization carries valuable structural and mechanistic information about the triplet states themselves and any ensuing radicals they later form. The origins of these processes and analysis of spin-polarized TREPR spectra will be presented and discussed.
Friday, November 6, 2009
Christine Payne, Assistant Professor of Chemistry, Georgia Tech
Imaging dynamic events inside living cells
Research in the Payne Lab is aimed at developing new technologies to observe dynamic events within living cells. Dynamics of interest include the enzymatic degradation of lipids and the intracellular regulation of redox state. This seminar will focus on recent results demonstrating the delivery of quantum dots to the cytosol of living cells. Quantum dots, nanometer-diameter semiconductor particles, have great potential for use as fluorescent probes for live cell imaging. They are many times brighter than traditional fluorophores, resistant to photobleaching, and can be conjugated to molecules for cellular targeting. Despite these advantages, the use of quantum dots for live cell imaging has been limited by the inability to deliver quantum dots to the cytosol of the cell using non-invasive methods. Using a combination of a cell-penetrating peptide and a hydrophobic counterion we have delivered quantum dots directly to the cytosol of living cells. Using single particle tracking, we have measured the diffusion coefficient of quantum dots within the cells and used this as a parameter to modify surface coatings for optimized intracellular targeting.
Friday, November 13, 2009
Kian Tian, Assistant Professor of Chemistry, Boston College
Catalytic Scaffolding Ligands: an efficient directing group strategy
There is a fundamental need to develop chemical transformations that are highly selective and atom-economical. Directing groups have played a pivotal role in controlling regio- and stereochemistry in a range of organic transformations. However, often directing-group strategies require the introduction of stoichiometric quantities of synthetically undesirable functional groups (such as phosphines) into the organic substrates. We are developing a new class of ligands that address this limitation. We have synthesized ligands that simultaneously and reversibly bind to a metal catalyst and common organic functional groups (such as alcohols and amines). By using a ligand as a scaffold to temporarily join the catalyst and substrate together, the power of directing groups to control selectivity is coupled to the practicality of catalysis. The value of the scaffolding strategy is that we can apply a synthetically useful functional group to bind to the ligand, and then tailor the ligand for optimal performance in the desired transformation.