2022 VICB Seminars
January 12: Lynmarie Thompson – University of Massachusetts (Zoom Only)
“NMR & Hydrogen Exchange of Chemoreceptor Complexes Suggest Signaling Occurs via Stabilization of a Disordered Domain”
Research Summary Points:
1) Native-like functional chemoreceptor complexes are used for biophysical studies of structure and mechanism
2) Solid-state NMR and HDX-MS identify disordered regions of component proteins
3) Kinase activation involves stabilization of both receptor and kinase domains
View the Zoom video of Dr. Thompson’s presentation.
January 19: Jim Shayman – University of Michigan (Zoom Only)
“The Design and Development of Substrate Reduction Inhibitors for Lysosomal Storage Disorders”
Areas of Interest
My lab develops small molecule inhibitors of glycosphingolipid synthases for use in lysosomal storage diseases. We have also discovered a novel lysosomal phospholipase A2 and are investigating its role in autoimmune disorders.
Clinical Interests
Diabetic renal disease and Fabry disease, and all aspects of general adult Nephrology, including chronic kidney disease (CKD).
January 26: BioVU Panel Discussion featuring Vanderbilt University Medical Center researchers Cheryl Gatto, Celeste Jones Paris, Robert Lavieri, Jillian Rhoads, and Michael Orr (Zoom)
“Bedside to Bench to Bedside: BioVU Resources in Discovery and Translational Research”
View the Zoom video of the BioVU Panel presentation.
February 2: John Albeck – University of California-Davis (Zoom Only)
“Signaling Rhythms that Coordinate Metabolism, Growth, and Inflammation in Single Cells”
Areas of Interest
1) Single-cell imaging of kinase networks regulating cell proliferation and metabolism
2) Understanding the mechanisms of information flow in signal transduction networks controlling cell growth, survival, and metabolism
View the Zoom video of Dr. Albeck’s presentation.
February 9: Lars Plate – Vanderbilt University (In-Person & Zoom)
“Revealing and Modulating Host Proteostasis to Target Virus Infections”
Research Overview:
The focus of the group is to define the dynamics and the coordination of protein
interaction networks in diverse cellular processes.
Our goal is to understand how protein interactions in the pertinent biological processes
have to be properly timed and coordinated.
View the Zoom video of Dr. Plate’s presentation.
February 16: Lars Dietrich – Columbia University (In-Person & Zoom)
“Metabolic Heterogeneity and Antibiotic Tolerance in Bacterial Biofilms”
Research Summary Points:
1) Multicellular structures, such as bacterial biofilms or tumors, contain gradients of resources, such as oxygen, and metabolites. These gradients determine the conditions of microniches and thereby promote physiological differentiation.
2) We study the metabolic strategies that allow bacteria to survive in multicellular structures,
with a focus on the pathogen Pseudomonas aeruginosa. These strategies include the use of oxygen-scavenging complexes and endogenous electron-shuttling compounds called phenazines. We have used microelectrodes to characterize gradients of oxygen and redox potential in P. aeruginosa biofilms. By coupling stimulated Raman scattering microscopy to a thin-sectioning technique we can profile metabolic activity along oxygen and redox gradients, and we have found that phenazines support metabolic activity in biofilm regions where oxygen is scarce.
3) Physiological differentiation in bioflms and tumors is thought to contribute to drug tolerance. Indeed, P. aeruginosa wild-type biofilms-which produce phenazines and show increased metabolic activity at depth-show increased antibiotic tolerance when compared to phenazine-null mutants.
View the Zoom video of Dr. Dietrich’s presentation.
February 23: Rudi Fasan – University of Rochester (In-Person & Zoom)
“Chemoenzymatic and chemobiosynthetic strategies for directing and expediting molecular discovery”
Research Summary:
This seminar will provide an overview of methodologies introduced by our laboratory as related to the late-stage C—H bond functionalization in complex natural products and to the synthesis and evolution of macrocyclic peptides for targeting protein-protein interactions.
March 2: Kendall Houk – UCLA (In-Person & Zoom)
“Pericyclic Reactions: Theory, Mechanisms, Dynamics, and Role in Biology”
Research Summary Points:
Pericyclic reactions were defined by Woodward and Hoffmann in the 1960s. Pericyclic reactions are concerted processes involving a cyclic reorganization of bonding. I will describe computational studies focusing on four recent discoveries:
1) defining mechanisms of these reactions in terms of dynamics of bonding changes
2) finding ambimodal polypericyclic transition states that give more than one product
3) explaining orbital symmetry forbidden reactions that nevertheless occur readily
4) identifying the role of pericyclic reactions in biosynthesis, catalyzed by a class of enzymes that we have named pericyclases
March 16: James Nowick – University of California-Irvine (Zoom Only)
“The Supramolecular Chemistry of the Antibiotic Teixobactin: How Basic Research on a New Antibiotic Has Provided New Insights and Exciting Opportunities”
Research Overview:
Our laboratory uses chemical model systems to understand the structures and interactions of peptides and proteins. We are especially interested in beta-sheets, because of their importance in amyloid and prion diseases. By using tools such as molecular modeling and design, chemical synthesis, NMR spectroscopy, X-ray crystallography, and cell-based assays, we aim to better understand the molecular basis for diseases such as Alzheimer’s, diabetes, and cancer.
View the Zoom video of Dr. Nowick’s presentation.
March 23: Derek Pratt – University of Ottawa (In-Person & Zoom)
“Endogenous and Exogenous Suppressors of Lipid Peroxidation and Associated Oxidative Cell Death”
Research Overview:
Research in the Pratt lab spans from pure chemistry (synthesis & mechanism) to applied chemistry (in biology & medicine) and generally, but not always, focuses on the reactions of radicals. The Pratt lab designs new reactions, synthesizes new molecules and uses them to explore the role of radicals – and develop strategies to control them – in contexts ranging from hydrocarbon oxidation to cell death.
April 6: Sheila David – University of California-Davis (In-Person & Zoom)
“DNA Repair, Chemistry & Cancer: It’s All About the Base”
Research Overview:
The David laboratory has focused extensively on the repair of oxidized guanines, and the base excision repair (BER) glycosylases MUTYH and NEIL1. Their present work is focused on dissecting the molecular features of the repair of myriad of substrates, including the hydantoins, processed by NEIL1 and the consequences of NEIL1 recoding.
April 13: Ryan Potts – Amgen (In-Person & Zoom)
“Drugging the Undruggable: Induced Proximity Medicines as the Next Wave of Drug Discovery”
April 20: Wendy Gordon – University of Minnesota (In-Person & Zoom)
“Decoding Mechanotransduction Mechanisms Using Molecular Tension Sensors”
Research Summary Points:
1) effects of Muscular Dystrophy mutations on cellular tension and mechanotransduction
2) new high-throughput molecular tension sensor
September 14: Justin Du Bois – Stanford University, “Using Chemistry to Study Voltage-Gated Ion Channels”
September 21: Stephen Fesik – Vanderbilt University, “Fragment-Based Drug Discovery”
September 28: Corey Hopkins – University of Nebraska, “Discovery and Characterization of Novel Small Molecules as In Vivo Tool Compounds” View Zoom Recording (VUNetID protected)
October 5: Scott Taylor – University of Waterloo, “Daptomycin and A54145D: A Tale of Two Antibiotics”
View Zoom Recording (VUNetID protected)
October 19: Jens Meiler – Vanderbilt University, “In Silico First – Ultra-Large Library Screening changes Drug Discovery in Academia”
View Zoom Recording (VUNetID protected)
October 26: Allison Walker, Vanderbilt University, “Machine Learning Strategies for Natural Product Discovery and Biosynthesis”
November 2: Maria Hadjifrangiskou – Vanderbilt University, “Powering the motor? Motility and Intracellular Pathogenesis of Uropathogenic E. coli”
November 9: Chang-Guo Zhan – University of Kentucky, “Drug Discovery and Development via Structure and Mechanism Based Molecular Design”
View Zoom Recording (VUNetID protected)
- State-of-the-art drug design should be based on not only the 3D structure of a given drug target, but also the detailed biomolecular mechanism (“structure and mechanism based design”).
- The structure and mechanism based molecular design is valuable for rational design of not only small-molecule drugs, but also protein drugs.
- The structure and mechanism based molecular design is valuable for not only drug discovery stage, but also the drug development stage.
November 16: Zhao-Qing Luo – Purdue University, “ADP-Ribosylation, Ubiquitination and Beyond by Legionella Virulence Factors”
View Zoom Recording (VUNetID protected)
November 30: Aaron Esser-Kahn – University of Chicago, “The Challenge of Making Every Vaccine Safer and More Effective: Engineering Signal Processing of Innate Immune Cells”
View Zoom Recording (VUNetID protected)
December 7: Hans Renata – Rice University, “Leveraging Biosynthetic Enzymes for Streamlining Access to Complex Molecules”
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- 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.