Seminars Archive

Spring 2018

Antibody affinity reagents and reproducibility: Strategies and challenges for the renewable diagnostics and therapeutics antibodies

Antibody affinity reagents and reproducibility: Strategies and challenges for the renewable diagnostics and therapeutics antibodies

Professor Bhupal Ban | UVA - Antibody Engineering & Technology Core

Professor Rebecca Pompano - *NOTE: (Dell 2 Room 100)

Learning Objectives

  •       Trends for isolation of monoclonal antibodies
  •       Current  antibody reproducibility problem in academic institute
  •       Antibody validation: Standards, policies, and practices 
  •       A new mindset for affinity application, evaluation, and authorization
  •       The advantages of recombinant antibody production methods over monoclonal and polyclonal antibody production methods.
  •       Phage display antibody production be adapted to produce the characteristic desired in applications such as multiple epitope recognition, tissues, and phenotype functional antibodies. 
  •       Learn about protein chemistry and conjugation of antibody and drug
  •       Immobilize antibody onto different polymers, nanoparticles, liposome  
Professor Bhupal Ban | UVA - Antibody Engineering & Technology Core
Hosted by Professor Rebecca Pompano - *NOTE: (Dell 2 Room 100)
Wednesday, February 21, 2018

In silico searches for (in)efficient electrocatalysts through chemical and material compound space

In silico searches for (in)efficient electrocatalysts through chemical and material compound space

Professor John Keith | University of Pittsburgh

Professor Charlie Machan

This talk will provide an overview of our group’s work using both standard and atypical high-performance computational chemistry modeling to elucidate atomic scale reaction mechanisms of catalytic reactions. I will introduce our toolkit of in silico methods for accurately modeling (electro)catalytic reactions in solvating environments. I will then present how in silico methods can be used for predictive insights into chemical and material design. The talk will then highlight our progress in modeling 1) the complex Morita-Baylis-Hillman reaction, 2) inefficient amorphous TiO2 materials as anti-corrosion coatings, and 3) biomimetic CO2 reduction mechanisms.

Professor John Keith | University of Pittsburgh
Hosted by Professor Charlie Machan
Friday, February 16, 2018

Interactions of antimicrobial and cell-penetrating peptides with lipid membranes

Interactions of antimicrobial and cell-penetrating peptides with lipid membranes

Professor Paulo Almeida | University of North Carolina at Wilmington

Professor Dave Cafiso

Antimicrobial, cytolytic, and cell-penetrating peptides, often called membrane-active peptides, belong to a variety of structural classes, including, alpha-helical, beta-sheet, unstructured, and cyclic polypeptides, among others. Those peptides were intensely studied in the 1990s and early 2000s with the hope of opening the door for urgently needed new antibiotics. For about 15 years we have studied the kinetics and thermodynamics of their interactions with lipid vesicles with the hope of understanding the mechanism of their function. In general, these peptides bind to lipid bilayers and somehow disrupt or perturb them, causing flux of ions and molecules across the membrane, and also, in some cases, translocating themselves across the membrane. In this talk, I will discuss our efforts to understand the mechanisms of these peptides and what we have learned regarding the effect of sequence on their ability to translocate across the membrane. I will conclude with the examination of a very different case, the cyclic peptide daptomycin, which is one of the few in clinical use. This peptide appears to behave very differently from all other membrane-active peptides that we have studied.

Professor Paulo Almeida | University of North Carolina at Wilmington
Hosted by Professor Dave Cafiso
Friday, February 2, 2018

Quantifying biochemistry in living cells

Quantifying biochemistry in living cells

Professor Amy Palmer | University of Colorado at Boulder

Professor Andreas Gahlmann

Increasingly, fluorescent tools are providing insight into the “dark matter” of the cellular milieu: small molecules, secondary metabolites, metals, and ions.  One of the great promises of such tools is the ability to quantify cellular signals in precise locations with high temporal resolution.  Yet this is coupled with the challenge of how to ensure that our tools are not perturbing the underlying biology and the need to systematically measure hundreds of individual cells over time.  The focus of research in the Palmer Lab is to develop fluorescent tools to illuminate and quantify biochemistry in living cells.  In addition to developing such tools, we strive to develop robust systematic analytical approaches for using sensors and fluorescence microscopy to carry out quantitative biochemistry at the single cell level.  Over the past 12 years our greatest effort has been in understanding the cell biology of zinc.  We have developed fluorescent sensors to map out the spatial distribution of zinc ions and quantify zinc dynamics in live mammalian cells.  These tools have allowed us to answer fundamental questions such as: where zinc is located in cells, how much is present in different kinds of cells, under what conditions zinc ions are dynamic, and how the zinc status of healthy cells differs from diseased cells.  Along the way, we have also established benchmark analytical approaches for using fluorescent sensors for quantitative biology and biophysics.  We have developed microfluidic cell sorting technologies to study and engineer fluorescent tools.  We have leveraged our expertise in fluorescent probes, single cell biology and live cell imaging to establish new methods for defining the complex dynamic interface between bacterial pathogens and host mammalian cells. And finally, we have started to expand our reach to develop chemical biology tools for labelling and tracking RNA in live cells.  This talk will provide a highlight of these research areas.

 

.

Professor Amy Palmer | University of Colorado at Boulder
Hosted by Professor Andreas Gahlmann
Friday, January 26, 2018

Transition metal catalyzed hydroarylation of Olefins: New catalysts for alkyl and alkenyl arenes

Transition metal catalyzed hydroarylation of Olefins: New catalysts for alkyl and alkenyl arenes

Professor Brent Gunnoe | University of Virginia

Professor Jill Venton
Professor Brent Gunnoe | University of Virginia
Hosted by Professor Jill Venton
Friday, January 19, 2018

Structural and dynamic studies of supramolecular assemblies by solid-state NMR spectroscopy

Structural and dynamic studies of supramolecular assemblies by solid-state NMR spectroscopy

Chris Jaroniec | Professor, Ohio State University

Professor Dave Cafiso

I will present recent work from my lab on the development and applications of magic-angle spinning solid-state nuclear magnetic resonance (NMR) techniques toward the structural and dynamic analysis of supramolecular protein and protein-DNA assemblies. The main topics will include: (1) new paramagnetic solid-state NMR methodologies for the rapid determination of three-dimensional protein structures and (2) studies of mammalian Y145Stop prion protein variants aimed at providing an atomic level structural basis for the phenomena of amyloid strains and cross-seeding barriers associated with these proteins. If time permits, I will also discuss our studies of the flexible histone N-terminal tail domains in large nucleosome arrays under experimental conditions corresponding to extended, folded and highly condensed chromatin.

Biosketch

Christopher Jaroniec received his B.S. degree in Chemistry from Kent State University in 1997 and his Ph.D. in Physical Chemistry from the Massachusetts Institute of Technology in 2003, where he was a National Science Foundation Graduate Research Fellow with Prof. Robert Griffin, and he was a Damon Runyon Cancer Research Foundation Postdoctoral Fellow with Dr. Ad Bax at the National Institutes of Health. He joined The Ohio State University as an Assistant Professor in 2006, was promoted to Associate Professor in 2011 and Professor in 2014, and named Evans Scholar in 2013. He currently also serves as the Vice Chair for Research and Administration in the Department of Chemistry and Biochemistry and the Director of the OSU CCIC Solid-State NMR Center, which houses multiple state-of-the-art high-field solid-state NMR instruments. Professor Jaroniec’s research in biomolecular solid-state NMR spectroscopy has been recognized by multiple awards including the NSF CAREER Award, the Eli Lilly Young Investigator Award in Analytical Chemistry, the Camille Dreyfus Teacher-Scholar Award, the Founders’ Medal from the International Council on Magnetic Resonance in Biological Systems, and the ACS Physical Division Early-Career Award in Experimental Physical Chemistry. He was also elected as Fellow of the American Association for the Advancement of Science and has held an Invited Visiting Professor position at Sorbonne Universités/Université Pierre et Marie Curie in Paris, France.

Chris Jaroniec | Professor, Ohio State University
Hosted by Professor Dave Cafiso
Friday, April 7, 2017

Colloidal metal nanocrystals: From academic studies to industrial applications

Colloidal metal nanocrystals: From academic studies to industrial applications

Younan Xia | Professor, Behrens Departamento de Quimica Inorganica Facultad de Quimica Universidad Nacional Autonoma de Mexico |

Professor Sen Zhang
Younan Xia | Professor, Behrens Departamento de Quimica Inorganica Facultad de Quimica Universidad Nacional Autonoma de Mexico |
Hosted by Professor Sen Zhang
Friday, March 17, 2017

Fall 2017

Confessions of a cunning collaborator: Strategies for sustaining a successful research agenda at a PUI

Confessions of a cunning collaborator: Strategies for sustaining a successful research agenda at a PUI

Professor Kristi Kneas | Elizabethtown College

Professor Jim Demas
Professor Kristi Kneas | Elizabethtown College
Hosted by Professor Jim Demas
Friday, November 17, 2017

From basic chemistry to new opioid biology

From basic chemistry to new opioid biology

Professor Jeff Aube | University of North Carolina, Chapel Hill

Professors Ken Hsu and John Lazo

The worldwide opioid crisis has occasioned efforts to develop new opioids for both existing uses (pain control) as well as new indications (itch, addiction). We have focused on the discovery of compounds able to selectively activate one of the two main intracellular pathways associated with the kappa opioid receptor. This type of activity, called “functional selectivity” or “ligand bias”, has the potential to segregate many of the ultimate biological effects of therapeutic opioids.

This project is an effort of a multidisciplinary, multi-institutional team led by the speaker and Professor Laura Bohn of the Scripps Research Institute.[1,2] It began with the development of a speculative library for screening against a range of potential biological targets based on a known but underexplored isoquinolinone synthesis. Applying this chemistry to library synthesis led to a hit compound that stoked our interest in biased ligand discovery, ultimately leading to the discovery of Triazole 1.1, a strongly biased KOR agonist with a fascinating in vitro and in vivo profile. These efforts and recent results will be described.

[1] Bohn, L.M.; Aubé, J. ACS Med. Chem. Lett, 2017, 8, 694–700.

[2] Brust, T. F.; Morgenweck, J.; Kim, S. A.; Rose, J. H.; Locke, J. L.; Schmid, C. L.; Zhou, L.; Stahl, E. L.; Cameron, M. D.; Scarry, S. M.; Aubé, J.; Jones, S. R.; Martin, T. J.; Bohn, L. M. Biased Agonists of the Kappa Opioid Receptor Suppress Pain and Itch Without Causing Sedation or Dysphoria. Sci. Signal. 2016, 9, ra117.

Jeffrey Aubé attended the University of Miami, where he did undergraduate research with Professor Robert Gawley (with whom he later co-authored the graduate text “Principles of Asymmetric Synthesis”, currently in its second edition). He received his Ph.D. in chemistry in 1984 from Duke University, working with Professor Steven Baldwin, and was an NIH postdoctoral fellow at Yale University with Professor Samuel Danishefsky. From 1986 until 2015, he held a faculty position in the Department of Medicinal Chemistry at the University of Kansas. In 2015, he retired from KU and moved to the University of North Carolina, where he is an Eshelman Distinguished Professor in the Division of Chemical Biology and Medicinal Chemistry. In addition to holding a joint appointment in the Department of Chemistry, Aubé is a member of the Center for Integrative Chemical Biology and Drug Discovery and the Lineberger Cancer Center.

Aubé’s research interests lie in the chemistry of heterocyclic compounds and their applications to problems in medicinal organic chemistry. The lab’s interests in bioorganic chemistry include collaborations in the area of opioid pharmacology (with Laura Bohn), steroid biosynthesis inhibitors (with Emily Scott), and in the discovery of anti-Mtb agents (with Carl Nathan). Aubé served as the principal investigator of the Chemical Methodology and Library Development Center program at Kansas as well as a specialized chemistry lab in the NIH’s Molecular Libraries Initiative.

Aubé has been honored for his research and scholarship by his receipt of awards from the American Chemical Society (including the Arthur C. Cope Scholar Award and the Midwest Award, bestowed by the St. Louis Section of the ACS) and for teaching (including the university-wide HOPE Award and the Kemper Fellowship for Teaching Excellence at KU). He is a fellow of both the American Association for the Advancement of Science and the American Chemical Society.

Professor Jeff Aube | University of North Carolina, Chapel Hill
Hosted by Professors Ken Hsu and John Lazo
Friday, November 10, 2017

Electrochemical power for future Army

Electrochemical power for future Army

Professor Cynthia Lundgren | Army Research Laboratory |

Professor Sen Zhang
Professor Cynthia Lundgren | Army Research Laboratory |
Hosted by Professor Sen Zhang
Friday, November 3, 2017

Redefining druggability using chemoproteomic platforms

Redefining druggability using chemoproteomic platforms

Professor Dan Nomura | University of California, Berkeley

Professor Ken Hsu
Professor Dan Nomura | University of California, Berkeley
Hosted by Professor Ken Hsu
Friday, October 27, 2017

A proton-coupled electron transfer viewpoint on bond activation electrocatalysis and nanocrystals

A proton-coupled electron transfer viewpoint on bond activation electrocatalysis and nanocrystals

Professor Jim Mayer | Yale University

Professor Charlie Machan
Professor Jim Mayer | Yale University
Hosted by Professor Charlie Machan
Friday, October 20, 2017

Once upon a time in Kamchatka: The extraordinary search for natural quasicrystals

Once upon a time in Kamchatka: The extraordinary search for natural quasicrystals

Professor Paul Steinhardt | Princeton University |

Professors Kateri DuBay and Jill Venton
Professor Paul Steinhardt | Princeton University |
Hosted by Professors Kateri DuBay and Jill Venton
Thursday, October 12, 2017

Assembly and disassembly of layered materials

Assembly and disassembly of layered materials

Professor Thomas Mallouk | Penn State University |

Professor Sen Zhang
Professor Thomas Mallouk | Penn State University |
Hosted by Professor Sen Zhang
Friday, October 6, 2017

Activity assisted self-assembly of colloidal particles

Activity assisted self-assembly of colloidal particles

Professor Angelo Cacciuto | Columbia University |

Professor Kateri DuBay
Professor Angelo Cacciuto | Columbia University |
Hosted by Professor Kateri DuBay
Friday, September 29, 2017

Designing nanoparticles for sustainability

Designing nanoparticles for sustainability

Professor Christy Haynes | University of Minnesota

Professor Rebecca Pompano

Engineered nanoparticles are increasingly being incorporated into devices and products across a variety of commercial sectors – this means that engineered nanoscale materials will either intentionally or unintentionally be released into the ecosystem. The long-term goal of the presented work is to understand the molecular design rules that control nanoparticle toxicity using aspects of materials science (nanoparticle design, fabrication, and modification), analytical chemistry (developing new assays to monitor nanotoxicity), and ecology (monitoring how nanoparticles enter and accumulate in the food web through bacteria and how these nanoparticles influence bacterial function). Taken together, these data suggest that careful consideration of engineered nanoparticle surface chemistry will likely allow design of safe and sustainable nanoscale materials.

Professor Christy Haynes | University of Minnesota
Hosted by Professor Rebecca Pompano
Friday, September 22, 2017

New recipes for biocatalysis: Expanding the cytochrome P450 chemical landscape

New recipes for biocatalysis: Expanding the cytochrome P450 chemical landscape

Professor Eric Brustad | University of North Carolina, Chapel Hill

Professor Ken Hsu

The design and engineering of protein catalysts that carry out rare or non-natural chemistry remains a challenging contemporary goal. However, enzymes are inherently limited by their chemical composition, i.e. the reagent pool that exists in nature and the amino acids and cofactors that form their physical and catalytic core. Because of this limitation, the majority of chemical transformations developed by synthetic chemists remain, at least to our knowledge, biologically inaccessible. Biological cofactors and prosthetic groups, including heme, provide a convenient means for natural proteins to increase their range of chemical transformations. Synthetic catalysts, similar to heme, demonstrate a wealth of chemical transformations, including metallocarbene insertion reactions, through mechanisms similar to native P450 catalysis; however, these reactions do not exist in biology due to the lack of the necessary ingredients in the cell or surrounding environment. By supplementing cytochrome P450s with non-natural reagents we have been able to demonstrate that a variety of natural enzyme scaffolds are capable of carrying out reactions, including the carbene-mediated cyclopropanation of olefins, not previously observed in the natural world. Moreover, as adaptable, genetically encoded systems, the activity and product regio- and stereochemical profiles of these catalysts can be tuned through mutation. We have shown that this non-natural chemistry can be applied for fine chemical synthesis, or even adapted to modify native P450 substrates. We have gone on to show that cytochrome P450s can be evolved for the incorporation of alternative metalloporphyrin scaffolds. By combining non-natural cofactor engineering with an increase in reagent diversity, we are generating orthogonal protein systems that deliver function not available to heme containing proteins.

 

Eric Brustad is a proud native of Indianapolis, Indiana. He graduated from Purdue University (W. Lafayette, IN) in 2002 receiving B.S. degrees in Chemistry and Biology as well as a B.A. in French. As an undergraduate, he began his research career in bioorganic chemistry under the mentorship of Jean Chmielewski. In the fall of 2002, he joined The Scripps Research Institute to carry out graduate research under the direction of Peter G. Schultz. His thesis work examined applications of unnatural amino acid mutagenesis to expand protein function. Dr. Brustad moved to the California Institute of Technology in December of 2008 as a Ruth Kirschstein postdoctoral fellow where he joined the group of Frances H. Arnold. While at Caltech, Dr. Brustad applied directed protein evolution to engineer proteins for non-natural catalysis or biosensing applications. In 2012, Eric joined the Department of Chemistry and the Carolina Center for Genome Sciences at the University of North Carolina at Chapel Hill. His research program focuses on combining chemical, biological and evolutionary approaches to expand the capabilities of living cells.  His honors include the Barry M. Goldwater Scholarship (2002), a Ruth L. Kirschstein National Research Service Award (2009), a DARPA Young Faculty Award (2013), and an NSF Career Award (2015).

Professor Eric Brustad | University of North Carolina, Chapel Hill
Hosted by Professor Ken Hsu
Friday, September 15, 2017

Searching for selective catalytic reactions in complex molecular environments

Searching for selective catalytic reactions in complex molecular environments

Professor Scott Miller | Yale University

Professor Mike Hilinski

This lecture will describe recent developments in our efforts to develop low-molecular weight catalysts for asymmetric reactions.  Over time, our view of asymmetry has ebbed and flowed, with foci on enantioselectivity, site-selectivity and chemoselectivity.  In most of our current work, we are studying issues of enantioselectivity as a prelude to extrapolation of catalysis concepts to more complex stereochemical settings where multiple issues are presented in a singular substrate.  Moreover, we continuously examine an interplay between screening of catalyst libraries and more hypothesis-driven experiments that emerge from screening results.  Some of the mechanistic paradigms, and their associated ambiguities, will figure strongly in the lecture.

 

Scott J. Miller was born on December 11, 1966 in Buffalo, NY. He received his B.A. (1989), M.A. (1989) and Ph.D. (1994) from Harvard University, where he worked with David Evans as a National Science Foundation Predoctoral Fellow.  Subsequently, he traveled to the California Institute of Technology where he was a National Science Foundation Postdoctoral Fellow with Robert Grubbs until 1996. For the following decade, he was a member of the faculty at Boston College, until joining the faculty at Yale University in 2006.  In 2008, he was appointed as the Irénée duPont Professor of Chemistry.

Professor Miller’s research program focuses on catalysis. His group employs strategies that include catalyst design, the development of techniques for catalyst screening, and the application of new catalysts to the preparation of biologically active agents.  Three current interests are (a) the selective functionalization of complex molecules, (b) the exploration of analogies between synthetic catalysts and enzymes and (c) the discovery of effective antibiotics despite increasing resistance.

Scott Miller’s awards and honors include: National Science Foundation CAREER Award (1999), Alfred P. Sloan Research Fellowship (2000), Camille Dreyfus Teacher-Scholar Award (2000), Arthur C. Cope Scholar Award of the American Chemical Society (2004), Yoshimasa Hirata Memorial Gold Medal of Nagoya University (2009), National Institutes of Health MERIT Award (2011), Fellow of the American Association for the Advancement of Science (2012), American Chemical Society Award for Creative Work in Synthetic Organic Chemistry (2016), Member, American Academy of Arts and Sciences (2016), Max Tishler Prize, Harvard University (2017).

Professor Miller has served in number of capacities for public and private organizations.  For example, he recently completed a term on the National Institute of General Medical Sciences Advisory Council, convened by the Director of the National Institutes of Health.  He now serves as Editor-in-Chief of The Journal of Organic Chemistry.

Professor Scott Miller | Yale University
Hosted by Professor Mike Hilinski
Friday, September 8, 2017

Expanding the imaging toolbox

Expanding the imaging toolbox

Professor Jennifer Prescher | University of California, Irvine

Professor Linda Columbus

Imaging tools have revolutionized our understanding of living systems by enabling researchers to “peer” into tissues and cells and visualize biological features in real time.  While powerful, these probes have been largely confined to monitoring cellular behaviors on a microscopic level.  Visualizing cellular interactions and functions across larger spatial scales—including those involved in cell migration to distant tissues, immunosurveillance, and other biological processes—remains a daunting task.  My research group is developing general toolsets to image such macroscopic cellular networks and behaviors, and our efforts are focused in two areas: generating novel bioluminescent probes and developing new bioorthogonal chemistries for imaging in vivo.

Professor Jennifer Prescher | University of California, Irvine
Hosted by Professor Linda Columbus
Friday, September 1, 2017

Fall 2018

TBA

TBA

Professor Lucy Ziurys | University of Arizona

Professor Rob Garrod
Professor Lucy Ziurys | University of Arizona
Hosted by Professor Rob Garrod
Thursday, September 21, 2017

2018

TBA

TBA

Professor Lucy Ziurys | University of Arizona

Professor Rob Garrod
Professor Lucy Ziurys | University of Arizona
Hosted by Professor Rob Garrod
Thursday, September 21, 2017

New Recipes for Biocatalysis: Expanding the Cytochrome P450 Chemical Landscape

New Recipes for Biocatalysis: Expanding the Cytochrome P450 Chemical Landscape

Professor Eric Brustad | University of North Carolina, Chapel Hill |

Professor Ken Hsu
Professor Eric Brustad | University of North Carolina, Chapel Hill |
Hosted by Professor Ken Hsu
Friday, September 15, 2017