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VICB Weekly Seminar Schedule - Fall 2013

Lawrence Marnett — Vanderbilt University
Wednesday, September 4, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"The Aspirin-Cannabinoid Connection – Discovering New Biological Pathways and Therapeutic Opportunities" 

Key Lecture Points:
·	The endogenous cannabinoid (endocannabinoid) signaling pathway 
·	Role of cyclooxygenase-2 (COX-2) in endocannabinoid signaling 
·	Structural biology of COX-2-endocannabinoid interactions 
·	Substrate-selective inhibition of COX-2-dependent endocannabinoid oxygenation 
·	Substrate-selective inhibitors as anti-anxiety agents in vivo

Billy Hudson — Vanderbilt University
Wednesday, September 18, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"The Sulfilimine Chemical Bond:  An Ancient Innovation Essential for the Genesis of Epithelial Tissues"

Key Lecture Points:
· Discovery of collagen IV and role in kidney diseases
· Discovery of the sulfilimine chemical bond in collagen IV
· Discovery of the essentiality of a trace element in bond formation and in tissue genesis
· Evolutionary origin of the sulfilimine bond

John Moult — University of Maryland
Wednesday, September 25 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Molecular Mechanisms Linking Genetic Variation to Disease"

Key Lecture Points:
· New genomic data = new insight into disease mechanisms
· Computational methods to explore that relationship
· The role of protein stability
· Roles of coding and expression changes in complex trait disease
· Leveraging GWAS to identify drug repurposing possibilities

Harold Schwalbe — University of Frankfurt
Wednesday, October 2, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"RNA-Based Regulation Monitored by NMR" 

Key Lecture Points:
· Molecular Mechanism of Riboswitch Function
· In Cell NMR of RNA riboswitches
· Prion Protein Aggregation Studied by NMR

Paul Workman — The Institute of Cancer Research UK
Wednesday, October 9, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Drugging the Cancer Genome: Chemical Biology of Molecular Chaperones and the Heat Shock Response"

Key Lecture Points:
·   Objective large-scale computational multidimensional analysis of cancer genome targets 
·   HSP90 inhibitors: From pathfinding chemical tools to clinical candidates
·   From target to clinical activity in breast and non small cell lung cancer with HSP90 inhibitor AUY922
·   Recent progress with the mechanism of action of HSP90 inhibitors
·   Chemical biology of HSP70 inhibitors
·    New targets on the HSF1-HSP90 pathway – identified by hypothesis-driven and high-throughput RNAi screening approaches
·    A new chaperone-deprivation mechanism for clinically approved protein kinase inhibitors

Christopher Lima — Memorial Sloan Kettering Cancer Center
Wednesday, October 23, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Post-Translational Modification by Ubiquitin-Like Proteins"

Key Lecture Points:
· Ubiquitin and ubiquitin-like protein conjugation pathways
· E1 activating enzymes, E2 conjugating enzymes and E3 ligases
· Conformational transitions accompany chemical steps

· Receptor specificity in signaling and recruitment

Annette Beck-Sickinger — Leipzig University 
Wednesday, October 30, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Ligand Binding Paths on G-Protein Coupled Receptors Revealed by Genetically Encoded Chemical Probes"

Key Lecture Points:
· Investigating structural elements of G-Protein Coupled Receptors (GPCRs) in the live cell
· Genetic incorporation of non-canonical amino acids into GPCRs
· Photo-crosslinking mapping of ligand binding sites on GPCRs
·
Novel bio-orthogonal chemistry to pin point ligand-receptor interactions
· Ligand binding paths in the transmembrane domain of class B GPCRs

Al Claiborne — Wake Forest School of Medicine
Wednesday, November 6, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Flavin-Linked Redox Networks as Underexploited Targets for Antibacterial Development"

Key Lecture Points:
· GSH synthesis is absent in many bacterial and protozoan pathogens
· Coenzyme A is a major GSH surrogate
· CoAS- mimetics as covalent coenzyme A-disulfide reductase inhibitors
·
A drug reprofiling approach with thioredoxin reductase
· A flavoenzyme as novel pneumococcal vaccine antigen

Arthur Palmer — Columbia University
Wednesday, November 13, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"From Fluctuations to Function: Molecular Recognition in the DNA Repair Enzyme AlkB and the Cell Adhesion Protein E-Cadherin"

Key Lecture Points:
· NMR spectroscopy allows characterization of rare, sparsely populated protein conformations
· Shift in equilibrium between ordered and disordered conformations of AlkB controls the sequence of binding of cosubstrates
       
and substrates
· On-pathway intermediate for dimerization of E-cadherin increases reaction kinetics to physiological time scales

Tina Iverson — Vanderbilt University
Wednesday, November 20, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Structure-Facilitated Bioengineering and Re-Evolving ACTive sites In Vitro (the Reactiv Project)" 

Key Lecture Points:
· Enzymes can be tuned to act on alternative substrates
· Rational design can complement random mutagenesis for engineering

· Evolutionary theories suggest how to improve bioengineering

Derek Tan — Memorial Sloan Kettering Cancer Center
Wednesday, December 4, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Diversity and Design: New Chemical Probes for Biology and Medicine"

Key Lecture Points:
· Current FDA approved drugs address a limited range of biological targets
· Natural products are known to interact with a wide variety of challenging targets
· Diversity-oriented synthesis provides access to natural product-based molecules for screening
·
Insights from natural products can also be leveraged in rational drug design

Torsten Schöneberg — Leipzig University
Wednesday, December 11, 2013 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
“Adhesion G Protein-Coupled Receptors - The Neglected Giants”

Key Lecture Points:
· The evolutionary origin of adhesion GPCRs
· Global structural aspects of adhesion GPCRs
· Human diseases/phenotypes related to variants in adhesion GPCRs
·
Ligand binding modes and signal transduction pathways
· Activation mechanism of adhesion GPCRs

   
 


VICB Weekly Seminar SchedulE - WINTER / SPRING 2014

Theresa Reineke —  University of Minnesota
Wednesday, January 8, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Sugar-Coated Complexes: Designed Polymers for Drug Delivery"

Key Lecture Points:
· Synthesis of novel polymers via RAFT polymerization
· BCS class II drug encapsulation, solubility enhancement, and oral drug delivery

· Plasmid DNA and siRNA complexation, characterization, and cellular delivery
· Systemic delivery of DNA and RNA drugs

Irene Coin — Leipzig University
Wednesday, January 15, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Ligand Binding Paths on G-Protein Coupled Receptors Revealed by Genetically Encoded Chemical Probes"

Key Lecture Points:
· Ligand based virtual screening
· Prioritize compounds for screening, acquisition, and synthesis

· Small molecules for gpcr drug discovery - mGlu, mc4, y4 receptors

Irene Coin — Leipzig University
Wednesday, January 29, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Ligand Binding Paths on G-Protein Coupled Receptors Revealed by Genetically Encoded Chemical Probes"

Key Lecture Points:
· Investigating structural elements of G-Protein Coupled Receptors (GPCRs) in the live cell
· Genetic incorporation of non-canonical amino acids into GPCRs
· Photo-crosslinking mapping of ligand binding sites on GPCRs
· Novel bio-orthogonal chemistry to pin point ligand-receptor interactions
· Ligand binding paths in the transmembrane domain of class B GPCRs

Stephen Traynelis — Emory University
Wednesday, February 12, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Control of NMDA Receptor Function by Allosteric Modulators"

Key Lecture Points:
· Discovery of subunit-selective positive allosteric modulators of NMDA receptor function
· Structure activity relationship for positive allosteric modulators

· Site of action of positive allosteric modulators
· In vivo activity of positive allosteric modulators

Liskin Swint-Kruse — University of Kansas Medical Center
Wednesday, February 19, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Rheostats and Toggle Switches for Modulating Protein Function"

Key Lecture Points:
· Nonconserved amino acid positions: important but seldom studied
· Design of a synthetic protein family for systematic, saturating mutagenesis of nonconserved positions

· Compare and contrast mutagenesis at nonconserved positions with mutagenesis at conserved positions
· Discriminating rheostat and toggle positions via bioinformatic analyses

Ned Porter — Vanderbilt University
Wednesday, February 26, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Oxysterols and a Human Syndrome: An Accidental Tour into Cholesterol Biosynthesis"

Key Lecture Points:
· Inborn errors in post-lanosterol sterol biosynthesis
· 7-Dehydrocholesterol, Smith-Lemli-Opitz syndrome
· Mechanisms of sterol free radical peroxidation
· Oxysterol reactivity and metabolism in cells and rodents
· Diels-Alder and Ene-chemistry based assays of cell culture and human plasmas

David Spiegel — Yale University
Wednesday, March 5, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Using Small Molecules to Engineer and Explore Human Immunity" 

Key Lecture Points:
· discovery of small molecule antibody-recruiting therapeutics for use in cancer and infectious diseases
· bifunctional small molecules redirect antibodies already present in the bloodstream to the surfaces of pathogenic cells

· ternary complexes formed between these agents, endogenous antibodies, and target cells lead to immune-mediated pathogen destruction
· strategy exploits many of the advantages of biologics while circumventing the disadvantages
· this strategy serves as a starting point toward entirely novel scientific insights and therapeutic approaches relevant to a wide range of disease states

Maria Hadjifrangiskou — Vanderbilt University
Wednesday, March 19, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Two-Component System Interactions as Uropathogenic E. coli Drug Targets"

Key Lecture Points:
· Molecular specificity determinants restrict signaling interactions among cognate receptor-regulator pairs
· In uropathogenic E. coli, the primary cause of urinary tract infections, non-partner interactions among two signaling pathways modulate responses to extracellular signals

· Biasing molecular interactions in these signaling cascades attenuates virulence and can be targeted for drug development

Andrea Robitzki — Leipzig University
Wednesday, April 9, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Functional Real-Time Analysis of GPCR in 3D Cell Systems: Screening of Y-Receptor-Ligands and Immunotoxins”

Key Lecture Points:

Part 1: Introduction of Lab-on-chip applications: Impedance spectroscopy and multi-parametric recordings (optoelectronic) of viable cells and tissues

Part 2: Impedimetric detection of neuropeptide Y receptor agonists and antagonists in viable mamma carcinoma cells by impedance spectroscopy
• Direct label-free quantification of neuropeptide Y (NPY) and Y1-receptor agonists in mamma carcinoma cells by impedance spectroscopy on 96-/384-well-titer plate-microelectrode arrays:
· Is it possible to measure the effect of NPY in Y1- and Y5-receptor expressing mamma carcinoma cells via impedance spectroscopy in real time?
· Is the physiological effect mediated by Y1- or Y5-receptor?
· Can ion channel activities be excluded causing a similar effect?
· Impedance spectroscopy – specific NPY receptor agonist studies

Part 3: An outstanding technique for the label-free real-time monitoring of novel polyionic linked immunotoxins in 3D carcinoma cultures
• Modular immunotoxins for targeted specific treatment of carcinoma: Quantitative and label-free real-time impedimetric detection of the immunotoxin efficacy
• Evaluating the capability of the impedance spectroscopy based 2D and 3D cell culture screening platform: Different penetration capacities of immunotoxin, neuropeptide Y (NPY) targeted toxin, and chemotherapeutics
• Different response rates of 2D and 3D carcinoma cultures to various chemotherapeutics and (immuno)toxins

Amanda Bryant-Friedrich — University of Toledo
Wednesday, April 9, 2014 — 4:00 P.M. to 5:00 P.M. — Stevenson Center 5211
"2-Deoxyribose Damage in DNA”     Co-Sponsored by the Center for Molecular Toxicology    Special Event!

Abstract:
Radical initiated DNA damage can be generated by the abstraction of one of five hydrogen atoms from the 2'-deoxyribose ring of the nucleic acid or through a variety of other mechanisms depending upon the nature of the oxidant. The result is the formation of a diversity of lesions, some of which compromise physiological processes. Our laboratory focuses on the generation and fate of 2-deoxyribose centered radicals that lead to DNA damage under a variety of conditions and a range of environments. Here results from our recent studies to determine the impact of nucleic acid structure on oxidative damage at the nucleic acid sugar will be presented. In addition, we have also developed a tool to investigate the role of radicals generated through the exposure of DNA to low-energy ionizing radiation in DNA damage processes. The application of this system to understanding the impact of low-energy electrons on DNA damage will also be discussed.

Heather Maynard — University of California-Los Angeles
Wednesday, April 23, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
"Protein Therapeutics Stabilized by Biomimetic Polymer Excipients and Conjugates" 

Key Lecture Points:
· Positive and drawbacks of protein therapeutics
· Biomimetics synthesized by controlled radical polymerization

· Mechanism trehalose polymers as protein stabilizers
· Biological activity of basic fibroblast growth factor (bFGF)
· Heparin mimetic polymers for bFGF stabilization

Kate Carroll — The Scripps Research Institute
Wednesday, April 30, 2014 — 12:15 P.M. to 1:15 P.M. — 1220 MRB III
“Painting the Cysteine Chapel: New Tools to Probe Oxidation Biology”

Key Lecture Points:
· Chemoselective methods for detecting cysteine oxidation
· Redox control of receptor tyrosine kinases

· Small molecules that target oxidized signaling proteins

   
   
   
   
   
   
   
   
   
   
   

 

 

 

 

 

 



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Chemistry Biology Interface (CBI) Seminar Schedule

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