Seminars Archive

Dr. Leah Dodson | University of Maryland, College Park

Professor Eric Herbst

Dr. Christina Cooley | Trinity University

Professor Mike Hilinski

Dr. Robert Gilliard | University of Virginia

Professor Jill Venton

Dr. Javier Grajeda | Eastman

Professor Brent Gunnoe

Dr. Ryan Fortenberry | University of Mississippi

Professor Robin Garrod

Dr. Charles Machan | University of Virginia

Professor Dean Harman

Special Seminar

Tuning the Reactivity Landscape of Metalloenzymes: From Active Site Modifications to Long-range Dynamic Effects | Dr. Paulo Zaragoza |University of California, Berkeley

UVA Rising Star in Chemistry Postdoctoral Seminar series

Join Zoom Meeting
https://virginia.zoom.us/j/91919004812?pwd=R0lGUGsvM2I4Y3dSVU85Nm9tQ0VXUT09

Meeting ID: 919 1900 4812
Passcode: 290863

Special Seminar

Modulation of MALT1 pre-mRNA structure by hnRNP proteins regulates T-cell activation | Dr. Alisha (Jonesy) Jones | Helmholtz Zentrum München, Munich, Germany

UVA Rising Star in Chemistry Postdoctoral Seminar series

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https://virginia.zoom.us/j/98531118370?pwd=dUVJd1Ria2QzdzR2MjZkcjJkM2pyUT09

Meeting ID: 985 3111 8370 Passcode: 103820

ACS Poster Session

Olfactory Receptors in Vascular Macrophages Drive Atherosclerosis by NLRP3-Dependent IL-1 Production

Klaus Ley, M.D. | La Jolla Institute for Immunology | Division Head/Professor Center for Autoimmunity and Inflammation

Professors Jill Venton and David Cafiso

Atherosclerosis is an inflammatory disease of the arterial wall driven by macrophages and other immune cells. Olfactory receptors (OLFRs) are G-protein coupled receptors expressed primarily in olfactory epithelium and are responsible for the sense of smell. OLFRs expressed in multiple extra-nasal tissues have been implicated in diverse biological processes. Here we show that mouse vascular macrophages express many olfactory receptors including Olfr2 (also known as I7), a receptor for octanal. They also express Rtp1, Rtp2, Adcy3, Gnal and the cyclic nucleotide-gated ion channel subunits Cnga1, 2, 3, 4 and Cngb1, accessory molecules needed for Olfr signaling and trafficking. Ligation of Olfr2 and its human orthologue (OR6A2), expressed in human atherosclerotic plaque and in human monocyte-derived macrophages, activates the NLRP3 inflammasome and, in synergy with LPS, induces secretion of IL-1α and β. Knocking out Olfr2 and Nlrp3 in mouse or knocking down OR6A2 in human macrophages abolishes IL-1β secretion in response to octanal. Mouse and human blood plasma contain micromolar levels of octanal, which are positively correlated with cholesterol and triglyceride levels. Boosting octanal levels exacerbates and knocking out Olfr2 significantly reduces atherosclerosis in the aortic arch and root. Our findings suggest that inhibitors of OR6A2 are promising targets for drug development to prevent and treat atherosclerosis-based cardiovascular diseases. 

2021 Hecht Lecture

Dr. Frank Bennett | Ionis Pharmaceuticals

Dr. Sidney Hecht

ABSTRACT

Antisense Oligonucleotide Therapeutics for Neurological Diseases

Antisense oligonucleotides (ASOs) are synthetic, chemical modified nucleic acid analogs designed to bind to RNA by Watson-Crick base paring and upon binding, modulate the function of the targeted RNA. There are a variety of mechanisms by which ASOs can modulate RNA function dependent on the chemical design of the ASO, the type of RNA and where on the RNA the ASO is designed to bind. Both protein coding, as well as non-coding RNAs, can be targets of ASO based drugs, significantly broadening therapeutic targets for drug discovery compared to small molecules and protein-based therapeutics. The recent approval of nusinersen (Spinraza™) as a treatment for spinal muscular atrophy (SMA) and inotersen (Tegsedi) for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR)  validates the utility of antisense drugs for the treatment of neurological  diseases. A summary of the progress, lessons learned and future challenges applying antisense technology for neurological diseases will be provided.

Membrane Partitioning by and for Cell Wall Synthesis

Dr. Sloan Siegrist | University of Massachusetts |

Professor Marcos Pires

Membrane Partitioning by and for Cell Wall Synthesis

Diffuse, sidewall patterning of cell wall peptidoglycan synthesis by the actin homolog MreB enables model organisms like Escherichia coli and Bacillus subtilis to maintain rod shape. Mycobacteria are also rods but grow from their poles and lack MreB. It is unclear how mycobacteria establish and propagate rod morphology. My lab has investigated the roles of the essential, cytoskeletal-like protein DivIVA (Wag31) and of inner membrane partitioning in polar growth and envelope assembly. Our work with the model organism M. smegmatis suggests that the membrane-cell wall axis is a self-organizing system in which DivIVA-directed cell wall synthesis organizes the inner membrane, and an organized inner membrane in turn makes cell wall synthesis more efficient and precise. These findings complement what has been reported for eukaryotic cell membranes, which can be partitioned by pinning to cytoplasmic structures such as the actin cytoskeleton and to external structures like extracellular matrix and cellulose. They are also congruent with the literature on model lipid bilayers, which can be phase separated by adhesive forces.

Manipulating Main Group Elements with Transition Metal Isocyanides

Dr. Joshua Figueroa | University of California, San Diego |

Professor Robert Gilliard

Manipulating Main Group Elements with Transition Metal Isocyanides

Abstract: Transition metal complexes supported by encumbering m-terphenyl isocyanides are adept platforms for the stabilization of unusual molecular species. It has recently been reported that an iron complex featuring two m-terphenyl isocyanide ligands can support a terminal boron monfluoride (BF) ligand. This simple 10e^– molecule is isoelectronic to carbon monoxide, but possesses vastly different electronic structure properties. In this presentation, the electronic features of metal-coordinated BF are discussed. In addition, the reactivity properties coordinated BF are detailed, with an emphasis on reactions where BF is the primary chemical protagonist. Highlighted are a series of reactions between the BF complex and nucleophilic substrates. In certain cases, nucleophiles are shown to displace fluoride from BF to generate new boron-containing ligands. These reactions are compared and contrasted with transformations where fluoride remains bound to the boron atom. Also presented are reactions between transition metal isocyanide anions and other substrates that generate uncommon metal-bound main group species.