Theo Humphreys

Structural Polymorphism of Solid Lipid Nanoparticles (LNPs) containing Natural Cholesterol Analogs

Lead Institution

Oregon State University

Principal Investigator

Gaurav Sahay

Lipid-based nanoparticles (LNPs) are the most advanced nanotherapeutics for the delivery of ribonucleic acids (RNA) for gene therapy. They are the only nanoparticles being used in the clinic for RNA…

Investigating the divergence of the major capsid protein within very closely related phage

Lead Institution

University of Connecticut

Principal Investigator

Simon White

The objective is to begin to understand the evolution of the HK97-like major capsid protein in the closely related actinobacteriophage (viruses that infect the Actinobacteria phylum). It will have…

Interrogating human immune response to vaccination

Lead Institution

Duke University

Principal Investigator

Priyamvada Acharya

The goal for HIV-1 vaccine design is to induce HIV-1–reactive broadly neutralizing antibodies (bnAbs). In this study we are focused on eliciting antibodies that target the binding site of the CD4…

Development of Copper Storage Protein Csp1 as an Electron-Dense “Bio Tag” for Facilitating Structural Determination of Small (< 100 kDa) Proteins by single-particle Cryo EM Methods.

Lead Institution

Oregon Health & Science University

Principal Investigator

David Farrens

Small (< 100 kDa) proteins are challenging to study by standard single-particle cryo-EM techniques, due to their very low signal to noise ratios in images. Heavy atoms could potentially overcome…

Conformational changes in Rag GTPases orchestrate signaling activities of mTORC1

Lead Institution

Whitehead Institute

Principal Investigator

David Sabatini

The mTORC1 protein kinase is a growth regulator that responds to stimuli, including nutrients and growth factors. Amino acids promote its translocation to the lysosomal surface, where it interacts…

Analysis of two dimensional crystals of membrane-bound HIV-1 proteins

Lead Institution

Oregon Health & Science University

Principal Investigator

Eric Barklis

Despite advances in AIDS diagnosis and treatment, the continuing AIDS epidemic demands continuing efforts to understand all aspects of HIV replication and to develop new methods for its inhibition…

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…

Structures of secondary membrane transporters

Lead Institution

New York University School of Medicine

Principal Investigator

Da-Neng Wang

We aim to determine the structures of several nutrient and drug transporter proteins. These membrane transporters play major physiological or pharmacological roles, and high resolution structural…

Cryo-EM studies of YiiP

Lead Institution

New York University School of Medicine

Principal Investigator

David Stokes

Cation Diffusion Facilitators are membrane transporters responsible for homeostasis of transition metals, such as Zn, Mn and Co. We are studying a bacterial homolog called YiiP, which like Znt…

Understanding the Molecular Mechanisms of P2X7 Receptor Signal Transduction

Lead Institution

Oregon Health & Science University

Principal Investigator

Steven Mansoor

P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP to modulate processes in the cardiovascular and immune systems. P2X7 receptor, the most structurally and…

The structural basis of histone variant H2A.Z-dependent chromatin regulation

Lead Institution

Stony Brook University

Principal Investigator

Dongyan Tan

The structural integrity and structural-dynamics of chromatin is of fundamental importance to all eukaryotes during normal development. Key factors in many genome regulation pathways exert their…

Investigation of Lipid Nanoparticle Internal Structure and Its Effect on Epithelial Cell Transfection

Lead Institution

Oregon State University

Principal Investigator

Gaurav Sahay

Lipid-based nanoparticles (LNPs) are a highly efficient way to encapsulate and safely transport nucleic acids past the cellular wall. In the last decade, nucleic acid therapeutics have expanded…

Structural and mechanistic studies of the CARD8 inflammasome

Lead Institution

Boston Children's Hospital

Principal Investigator

Hao Wu

Innate immunity comprises ancient and evolutionarily conserved biological pathways that are imperative for the recognition of pathogens and endogenous damage. One such major signaling axis termed the…

Structural characterization of inositol triphosphate receptors

Lead Institution

Vanderbilt University

Principal Investigator

Erkan Karakas

The overall goal of the research studies proposed here is to structurally characterize the inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs). IP3Rs are tetrameric intracellular Ca2+ channels that…

Structural investigation of the PI3K-gamma isoform kinase

Lead Institution

University of British Columbia

Principal Investigator

Calvin Yip

One of the major developments in cancer treatment has been the use of cancer immunotherapy to utilize the immune system to target and destroy cancer cells. The phosphoinositide 3-kinase (PI3K)…

Structure determination of non-coding RNAs

Lead Institution

University of California, San Diego

Principal Investigator

Navtej Toor

Non-coding RNAs (ncRNA) play many diverse but essential roles in biology. Among the first characterized ncRNAs are transfer RNAs, ribosomal RNAs, and the spliceosomal RNAs. Later on, researchers…

Structural studies on chromatin assembly complexes

Lead Institution

Korea Advanced Institute of Science and Technology (KAIST)

Principal Investigator

Ji-Joon Song

Nucleosome is the fundamental unit of DNA high-order structure called chromatin. Nucleosome is a complicated structure composed of four different histones and DNA. The assembly of nucleosome is…

Elucidating Native Structures of Enveloped Virus Glycoproteins using Cryo-EM and Tomography

Lead Institution

University of British Columbia

Principal Investigator

Sriram Subramaniam

We seek to understand the entry mechanisms of enveloped viruses for three viral families having broad health impact worldwide: coronaviruses such as SARS CoV 2, retroviruses such as HIV 1, and…

Structural characterization of restriction/modification enzyme BsaXI complex with DNA target for structure-based design of gene-targeting reagents

Lead Institution

Fred Hutchinson Cancer Research Center

Principal Investigator

Betty Shen

Genome engineering and targeted gene modification is a rapidly maturing discipline in which genomes within cell lines, tissues or organisms are manipulated and altered at specified individual loci…

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…

Structure and mechanism of human diacylglycerol O-acyltransferase-1

Lead Institution

Baylor College of Medicine

Principal Investigator

Ming Zhou

Diacylglycerol O-acyltransferase-1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in mammals. DGAT1 belongs to the superfamily of membrane-bound O…

Solving the Structure of Eukaryotic Type III Glutamine Synthetase Assembles

Lead Institution

Environmental Molecular Sciences Laboratory

Principal Investigator

James Evans

There are three major classes of the enzyme Glutamine Synthetase (GS) that share widely conserved active-site residues but vary in average protein length, oligomeric assembly state and cofactor…

Structure determination of full-length amyloid fibrils of protein tau seeded by fibrils extracted from brains of Alzheimer’s Disease (AD) patients

Lead Institution

University of California, Los Angeles

Principal Investigator

David Eisenberg

The accumulation of amyloid fibrils in the brain is associated with physiological events that trigger cascades of numerous neurodegenerative diseases. Here, we aim to use cryo-EM to determine the…

Structures and gating mechanisms of the inward rectifier potassium channel Kir7.1

Lead Institution

University of Michigan

Principal Investigator

Alys Peisley

Inwardly rectifying K+ (Kir) channels are an important class of K+ channels that conduct K+ ions on hyperpolarization, rather than on depolarization as in other K+ channels. We are using cryo-EM to…

Cryo-EM studies of novel antibiotics bound to the ribosome of the multi-drug resistant organism Acinetobacter Baumannii

Lead Institution

Case Western Reserve University

Principal Investigator

Edward Yu

The global rise in Multiple Drug Resistant (MDR) bacteria promises to make curing common infections impossible, claiming a spot on the Top Ten Threats to Global Health list published by the World…

Structure and conformational dynamics of biologically important RNAs

Lead Institution

University of Colorado Anschutz Medical Campus

Principal Investigator

Jeffrey Kieft

RNA’s remarkable functional diversity is conferred by its ability to adopt a seemingly endless variety of structures and undergo programmed conformational dynamics. The emergence of cryo-EM as a…

Novel biochemical methods for facilitating GPCR tertiary and quaternary structure determination by cryo-EM.

Lead Institution

Oregon Health & Science University

Principal Investigator

David Farrens

GPCRs are the largest family of membrane proteins in the human genome, and a major target of pharmaceutical drugs. However, relatively few GPCR structures are known. Moreover, many GPCRs are known…

Visualizing a dynamically tethered DEAD-box ATPase-rRNA complex during ribosome maturation-

Lead Institution

University of Texas Southwestern Medical Center

Principal Investigator

Jan Erzberger

The assembly of ribosomes is a critical process in cells, and its dysregulation contributes to a range of human diseases termed ribosomopathies. Ribosome maturation relies on numerous enzymes, most…

Structural studies of the targeting factor Get3

Lead Institution

California Institute of Technology

Principal Investigator

William Clemons

Tail-anchored (TA) proteins, accounting for approximately 2% of the genome, are a class of proteins with various functions but all with a single transmembrane domain near their C-terminus. Due to the…

COVID19: Structure of COVID19 SARS-CoV-2 Spike protein in complex with monoclonal antibodies.

Lead Institution

Fred Hutchinson Cancer Research Center

Principal Investigator

Marie Pancera

The ongoing global outbreak of atypical pneumonia (COVID-19) is caused by a newly emerged zoonotic beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1). On March 11th,…

Structural Characterization of Schistosome Vault Particles

Lead Institution

University of Chicago

Principal Investigator

Minglei Zhao

Schistosomiasis is a disease caused by parasitic flatworm schistosome, and affects about 252 million people each year. In tropical countries, schistosomiasis is second only to malaria among parasitic…

Structural Analysis of human retinal ABCA4 using single particle cryo-electron microscopy

Lead Institution

University of British Columbia

Principal Investigator

Robert Molday

Stargardt disease (STGD1) is an autosomal recessive, early-onset macular dystrophy associated with reduced visual acuity and a progressive loss in vision. The gene responsible for STGD1 encodes ABCA4…

Characterization of Novel Biocompatible Carbon Nanomaterials

Lead Institution

University of Oregon

Principal Investigator

Benjamin McMorran

Carbon nanohoops ([n]cycloparaphenylenes or CPPs) are tunable building blocks with applications in fluorescence microscopy, nanotechnology, and electronics. The nanohoop units are biocompatible…

Determination of RAD52 and replication fork DNA complex

Lead Institution

University of Iowa

Principal Investigator

Maria Spies

RAD52 is an emerging target for drug discovery targeting DNA repair-deficient tumors. The exact cellular functions and structural mechanisms of RAD52, however, remain unresolved. This proposed…

Structural investigation of transcription reprogramming by E. coli stringent starvation protein A

Lead Institution

Duke University

Principal Investigator

Maria Schumacher

Stringent starvation protein A (SspA) is a global transcriptional regulator that associates with RNA polymerase (RNAP) and plays roles in the activation of the stringent response and pathogenesis in…

Structural studies of chromatin complexes involved in human diseases

Lead Institution

Pennsylvania State University

Principal Investigator

Song Tan

The nucleosome is a fundamental unit of chromatin and the target of a host of gene regulatory chromatin enzymes and proteins. It consists of DNA wrapped around a protein core, composed of histones…

Understanding the evolution of the coat protein fold using P22-like phages

Lead Institution

University of Connecticut

Principal Investigator

Carolyn Teschke

Despite very low sequence homology, the major capsid proteins of dsDNA bacteriophages, some archaeal viruses and the herpesviruses, share a common structural motif - the HK97-fold. My group is…

Synthesis and rational design of next-generation ribosome-targeting inhibitors

Lead Institution

University of California, San Francisco

Principal Investigator

James Fraser

Antibiotic resistance is an urgent threat to public health. CryoEM of the bacterial ribosome affords insight into the interactions between organic inhibitor scaffolds, the RNA, and even the nascent…

Structural studies of a bacterial siderophore ABC importer YbtPQ

Lead Institution

University of Colorado Anschutz Medical Campus

Principal Investigator

Hongjin Zheng

Iron (Fe) is an essential element for not only the well-being of hosts, but also the growth and virulence of microbes(Begg, 2019). One of the major Fe uptake processes in bacteria is through…

Cryo-EM of Metabolic Enzymes for Drug Design

Lead Institution

University of British Columbia

Principal Investigator

Sriram Subramaniam

Given the high failure rate of drug candidates that enter clinical trials and the length of time involved, there is an urgent need to develop new approaches to lower failure rates. Some of the…

Projects