Nancy Meyer

Structure / Function Analysis of Positive-Strand RNA Virus Replication Complexes

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Paul Ahlquist

Positive-strand RNA ((+)RNA) viruses, the largest genetic class of viruses, include numerous major pathogens such as the Zika, MERS, SARS and hepatitis C viruses. A key target for understanding and…

Dissecting bacterial secretion systems in situ with electron cryo-tomography

Lead Institution

California Institute of Technology

Principal Investigator

Grant Jensen

Pathogenic bacteria use specialized “nanomachines” to identify and interact with host cells. These machines are attractive drug targets because they are surface-exposed, widespread, and vital for…

KATP channel structures

Lead Institution

Oregon Health & Science University

Principal Investigator

Show-Ling Shyng

ATP-sensitive potassium (KATP) channels couple cell metabolism to membrane excitability and are important for regulating hormone secretion, neuronal activity, vascular tone, and adaptive response to…

Structural basis for recognition of receptor CSPG4 by Clostridium difficile toxin B

Lead Institution

University of California, Irvine

Principal Investigator

Rongsheng Jin

Clostridium difficile (C. diff) is an opportunistic pathogen, which establishes in the colon when the gut microbiota is disrupted by antibiotics or diseases. C. difficile infection (CDI) leads to…

Structural insights into the regulation of MDA5-mediated antiviral signaling activity

Lead Institution

Boston Children's Hospital

Principal Investigator

Sun Hur

Effective antiviral immunity involves the recognition of viral dsRNA by the innate immune receptor MDA5 and the subsequent interferon signaling cascade. Aberrant recognition of endogenous “self” RNAs…

Interactions of Adeno-associated virus (AAV) with its Cellular Receptor, RAAV

Lead Institution

University of Missouri - Columbia

Principal Investigator

Michael Chapman

AAV is a leading vector for gene therapy, and, through genomic screening, we recently identified the cellular receptor, AAVR. Biochemistry, and early cryo-EM indicate that the different serotype…

Active Structure of ClpX Bound to SsrA substrate

Lead Institution

University of Utah

Principal Investigator

Christopher Hill

AAA+ ATPases are involved in myriad cellular functions, including cell membrane reformation, chromatin remodeling, protein degradation and quality control. Our lab is investigating the mechanism,…

Structural basis for translocon modulation

Lead Institution

University of Helsinki

Principal Investigator

Ville Paavilainen

Nearly 95% of human secretory and integral membrane proteins are cotranslationally targeted to the Sec61 translocon, which facilitates transport of these proteins into the ER lumen or lipid bilayer…

Mapping the transport cycle of asymmetric ABC transporters.

Lead Institution

University of Arizona

Principal Investigator

Thomas Tomasiak

ATP binding cassette (ABC) transporters play vital roles in maintaining both the composition of cell membranes and the identity of molecules traveling across them. In particular, many ABC…

Cryo-EM study of alpha-synuclein fibrils with hereditary disease mutation

Lead Institution

University of California, Los Angeles

Principal Investigator

Lin Jiang

With recent advances of cryo-EM technologies, including direct electron detecting cameras, we are now able to probe a broad scope of amyloid fibril structures to a level of molecular detail that has…

Visualizing stimulated chromatin regulatory proteins bound to substrate

Lead Institution

New York University School of Medicine

Principal Investigator

Karim Armache

The regulation of gene activity is a key regulatory process during cellular differentiation and is a crucial requirement for development in multicellular organisms. A large number of mechanisms have…

Structural studies of large clostridium toxins

Lead Institution

University of California, Irvine

Principal Investigator

Rongsheng Jin

Bacterial toxins are virulence factors that manipulate host cell functions and cause a myriad of serious diseases. We propose two aims to study the structure and function of Clostridium difficile…

TheThe Streptococcus pneumoniae IgA1 Protease: from molecular mechanism to vaccine development.

Lead Institution

University of Colorado at Denver

Principal Investigator

Elan Eisenmesser

Streptococcus pneumoniae remains a “major global public health problem” according to the World Health Organization with an alarming increase in non-vaccine serotypes, prompting the immediate need to…

Molecular mechanisms and inhibition of metabolic acyltransferase enzymes

Lead Institution

University of Pennsylvania

Principal Investigator

Ronen Marmorstein

The goal of this project is to determine the cryo-EM structures of metabolic acyltransferase enzymes in functionally relevant reaction states and bound to inhibitors to elucidate their molecular…

Looking at the high-resolution structure of IRE1 inside cells using sub-tomogram averaging

Lead Institution

California Institute of Technology

Principal Investigator

Grant Jensen

The primary objective of our proposal is to image IRE1 foci using high-resolution cellular electron cryo-tomography (ECT). IRE1 is a member of the unfolded protein response (UPR). The UPR is an…

Structural characterization of the Helicobacter pylori Cag T4SS using single particle cryo-EM

Lead Institution

University of Michigan

Principal Investigator

Melanie Ohi

Using cryo-EM we determined the structure of the 5.6 MDa H. pylori Cag T4SS at a resolution of ~3.6 Å. The Hp T4SS is structurally different from T4SS structures seen in other species and has an…

Determining structural mechanisms of transporters and signaling networks in cellular stress responses

Lead Institution

University of Arizona

Principal Investigator

Thomas Tomasiak

Rapidly dividing or invasive cells tied to diseases such as cancer, fungal or bacterial infection require responses that enable their survival during nutrient deprivation and drug therapy. Tightly…

Imaging Transcriptional Complexes by CryoEM

Lead Institution

Emory University

Principal Investigator

Eric Ortlund

Nuclear receptors (NRs) sense changes in lipid metabolite levels to trigger specific patterns of gene regulation, which drive critical biological processes including metabolism, development, and…

Investigations of host-pathogen interactions and cellular structures with cryo-electron microscopy

Lead Institution

University of Wisconsin, Madison

Principal Investigator

Elizabeth Wright

The Wright laboratory uses cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) to study biological problems in structural cell biology and infectious disease. We are…

CryoEM structures of pancreatic KATP channels

Lead Institution

Oregon Health & Science University

Principal Investigator

Show-Ling Shyng

The ATP-sensitive potassium (KATP) channel formed by four Kir6.2 and four SUR1 subunits regulate insulin secretion in ?-cells by coupling glucose metabolism with membrane excitability. Mutations in…

Investigating substrate channeling and cooperativity in assembly-line terpenoid synthases.

Lead Institution

University of Pennsylvania

Principal Investigator

David Christianson

Bifunctional assembly-line terpenoid synthases catalyze a specific sequence of chemical reactions starting with simple 5-carbon precursors, and ending with 20- or 25-carbon polycyclic natural…

The cryoEM structures of the MMOH-MMOR complex

Lead Institution

University of Michigan

Principal Investigator

Uhn-soo Cho

Methane to methanol conversion is critical for environmental health, reducing greenhouse gas, and utilizing the natural gas as an alternative energy source. Methanotrophic bacteria utilize the…

Cryo-EM structure of the human ATP-citrate lyase (ACLY) bound to inhibitors

Lead Institution

University of Pennsylvania

Principal Investigator

Ronen Marmorstein

The goal of this project is to determine the cryo-EM structure of the human ATP-citrate lyase (ACLY) multimer bound to inhibitors to better understand the mechanism of ACLY activity and to generate a…

Cryo-EM structure of the FACT-histone complex

Lead Institution

University of Michigan

Principal Investigator

Uhn-soo Cho

The FACT complex, composed of hSpt16 and SSRP1 in human, was initially discovered as a factor that is essential for transcription elongation. It functions as an ATP-independent histone chaperone to…

Mechanism of translational regulation and mRNA quality control

Lead Institution

California Institute of Technology

Principal Investigator

Rebecca Voorhees

In all kingdoms of life proteins are synthesized by the large ribonucleoprotein particle known as the ribosome. However it is increasingly clear that the ribosome serves not only as a hub for protein…

Tom1/HUWE1 and its interaction with Spt6

Lead Institution

University of Utah

Principal Investigator

Christopher Hill

Our lab reported that the transcriptional regulator, Spt6, contains a tandem-SH2 domain that binds RNA pol II through a novel interaction that requires multiple phosphorylation site on the Rpb1…

Investigating the cytoplasmic domain architecture of the Legionella pneumophila type IV secretion system using sub-tomogram averaging

Lead Institution

California Institute of Technology

Principal Investigator

Grant Jensen

In fresh water environment, Legionella pneumophila relies on its Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effector proteins into its protozoan host. This process is…

IR-A agonist structures

Lead Institution

University of Utah

Principal Investigator

Christopher Hill

Our goal is to determine the structure of the insulin receptor (IR) ectodomain bound to non-insulin peptide modulators of the receptor. We are studying two peptides that share a high degree of…

Structure of the first purified manganese oxidase Mnx

Lead Institution

University of Washington

Principal Investigator

Bradley Tebo

Microbial production of manganese oxide (MnO2) is a globally important biomineralization process. MnO2 is a key component of the Mn cycle, which supports life through the Mn catalytic centers of many…

Collaborative Access Team: Pacific Northwest Cryo-EM Center (PNCC)

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

James Evans

PNNL will create and operate the Pacific Northwest Center for Cryo-EM (PNCC), a state-of-the-art national center for cryo-electron microscopy (Cryo-EM) that will rapidly and efficiently collect and…

Screening of a Candida albicans drug resistance transporter MLT1

Lead Institution

University of Arizona

Principal Investigator

Thomas Tomasiak

Fungal infections present a rising and underappreciated threat to health. The CDC identified one species of fungal infections, Candida, as one of 18 leading antibiotic resistant infection threats…

EMSL Science Overview

Nancy Meyer

Projects

Structure / Function Analysis of Positive-Strand RNA Virus Replication Complexes

Dissecting bacterial secretion systems in situ with electron cryo-tomography

KATP channel structures

Structural basis for recognition of receptor CSPG4 by Clostridium difficile toxin B

Structural insights into the regulation of MDA5-mediated antiviral signaling activity

Interactions of Adeno-associated virus (AAV) with its Cellular Receptor, RAAV

Active Structure of ClpX Bound to SsrA substrate

Structural basis for translocon modulation

Mapping the transport cycle of asymmetric ABC transporters.

Cryo-EM study of alpha-synuclein fibrils with hereditary disease mutation

Visualizing stimulated chromatin regulatory proteins bound to substrate

Structural studies of large clostridium toxins

TheThe Streptococcus pneumoniae IgA1 Protease: from molecular mechanism to vaccine development.

Molecular mechanisms and inhibition of metabolic acyltransferase enzymes

Looking at the high-resolution structure of IRE1 inside cells using sub-tomogram averaging

Structural characterization of the Helicobacter pylori Cag T4SS using single particle cryo-EM

Determining structural mechanisms of transporters and signaling networks in cellular stress responses

Imaging Transcriptional Complexes by CryoEM

Investigations of host-pathogen interactions and cellular structures with cryo-electron microscopy

CryoEM structures of pancreatic KATP channels

Investigating substrate channeling and cooperativity in assembly-line terpenoid synthases.

The cryoEM structures of the MMOH-MMOR complex

Cryo-EM structure of the human ATP-citrate lyase (ACLY) bound to inhibitors

Cryo-EM structure of the FACT-histone complex

Mechanism of translational regulation and mRNA quality control

Tom1/HUWE1 and its interaction with Spt6

Investigating the cytoplasmic domain architecture of the Legionella pneumophila type IV secretion system using sub-tomogram averaging

IR-A agonist structures

Structure of the first purified manganese oxidase Mnx

Collaborative Access Team: Pacific Northwest Cryo-EM Center (PNCC)

Screening of a Candida albicans drug resistance transporter MLT1