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9873 documents

Towards high-resolution structural biology of membrane protein complexes in their native lipid environment

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Doreen Matthies · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · 2021 · $987,868 — (1) Structural and functional investigation of CXCR3 chemokine receptor in its role in recurrent miscarriage Recurrent miscarriage (RM) is usually defined as the loss of three or more consecutive pregnancies prior to the 20th week of gestation affecting approximately 1% of women of reproductive age.…

Micro Analytical Immunochemistry

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Heather Kalish · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · 2021 · $741,947 — Sub-project #1 MALDI imaging of tissue samples to identify novel proteins MALDI-TOF Imaging is an emerging tool for the label free measurement of peptides, proteins, lipids, drugs and metabolites. The tissue can be imaged directly be the MALDI-TOF and combined with other modalities to study the mo…

Paramyxoviruses as Vaccine Vectors Against Highly Pathogenic Viruses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Ursula Buchholz · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $215,100 — We previously constructed a first-generation construct called HPIV3-EbovZ GP, in which the complete genome of the JS strain of HPIV3 was modified by the addition of the Ebov GP gene in the third gene position, between the HPIV3 P and M genes. The JS strain is thought to be an attenuated HPIV3, based…

Biobehavioral Imaging and Molecular Neuropsychopharmacology of Substance Abuse Mechanisms

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Michael Michaelides · NATIONAL INSTITUTE ON DRUG ABUSE · 2021 · $1,630,210 — The societal and economic burden of substance use disorders is vast and ever-increasing. To address this requires developing innovative therapeutics, an approach necessitating a deep understanding of behavior and its neurobiological basis. Fortunately, the last decade has witnessed a surge of breakt…

Pre-clinical Vaccine Development for Emerging and Re-emerging Infectious Diseases

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

John Mascola · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $3,934,150 — The Virology Core has collaborated with other intramural NIAID labs to develop a MERS-CoV Spike protein subunit vaccine. A vaccine of adjuvanted MERS-CoV Spike protein subunit vaccine confers complete protection from MERS-CoV disease in alpaca and results in reduced and delayed viral shedding in the…

Biological Sequence Quality Control and Organization

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Eric Nawrocki · NATIONAL LIBRARY OF MEDICINE · 2021 · $187,304 — During the past year, we improved our software package VADR (https://github.com/nawrockie/vadr) for viral sequence annotation using models based on RefSeq annotation. VADR aligns complete input sequences to their nearest RefSeq sequence and uses that alignment to map the RefSeq annotation onto the i…

Structural and functional studies of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts)

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Nadine Samara · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · 2021 · $467,822 — GalNAc-Ts are Golgi-membrane anchored enzymes containing 2 luminal domains that dictate substrate specificity: a catalytic domain and a C-terminal lectin domain consisting of 3 repeats (alpha, beta, gamma) that can potentially recognize and bind extant GalNAcs on glycoprotein or glycopeptide substra…

Pathogenesis, Treatment and Prevention of Emerging Infectious Diseases

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

H. Clifford Lane · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $155,251 — Research in this project is currently focused on six areas. These are: characterization of the survivors of the anthrax attacks of 2001; characterization of emerging respiratory infections including SARS, COVID-19, and influenza; evaluation of experimental vaccines and treatments for Ebola virus; c…

COVID-19: Identification and Development of Clinical Candidates to Treat SARS-CoV-2

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Donald Lo · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2021 · $3,643,319 — We have worked in collaboration with experts in and outside of NIH on the development of 8 assays for use in repurposing screens of approved drug collections to identify compounds active against SARS-CoV-2. The compounds identified from such screens have potential for clinical trials as single agent…

Molecular imaging of viral infections

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Dima A Hammoud · CLINICAL CENTER · 2021 — Sars-Cov-2 project: We have started our experiments by developing the LPS lung injury model by administering LPS intratracheally. We are using male and female mice, including WT and ACE2 Transgenic mice. At this stage we are imaging the lung infiltrates and assessing ACE2 levels in the various group…

COVID-19: Assay Development, HTS and Drug Repurposing to identify potential therapeutics against SARS-CoV-2

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Matthew Hall · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2021 · $462,178 — During this past reporting period, NCATS began development of over a dozen novel assays to screen for potential therapeutic agents against SARS-CoV-2. Optimized assays were then screened against a panel of drug repurposing, clinical candidate and antiviral libraries that have been assembled at NCAT…

Development of COVID-19 cell entry inhibitors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Nadya Tarasova · DIVISION OF BASIC SCIENCES - NCI · 2021 · $61,708 — The reliability, and consequently success of virtual screening depends heavily on the accuracy of the x-ray structure depiction of the target protein structure in solution. Crystal packing can distort conformation of flexible parts of the protein thus leading to misrepresentation of the protein stru…

Antagonism of Coronavirus Spike Proteins by Cellular Host Factors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

eric freed · DIVISION OF BASIC SCIENCES - NCI · 2021 · $18,681 — In a structural and functional analysis of the SARS-CoV-2 S protein that we recently started, we have determined that MARCH8, but not a catalytically inactive MARCH8 mutant, targets the S proteins of SARS-CoV, MERS-CoV, and SARS-CoV-2 for degradation. We also showed that human airway epithelial cell…

Transgenic Resources for Neuroscience Research

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

James Pickel · NATIONAL INSTITUTE OF MENTAL HEALTH · 2021 · $2,338,230 — Summary 1) Production of rodent transgenics Metrics of production over the past year include the following projects: a) 19 transgenic rodent projects produced by CRISPR constructs, with multiple lines produced for each project in rats (4) or mice (15). b) only 4 projects used legacy methods to make…

Serologic studies of persons with COVID-19 infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Jeffrey Cohen · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $11,170 — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is associated with respiratory-related disease and death. Assays to detect virus-specific antibodies are important to understand the prevalence of infection and the course of the immune re…

COVID-19 Serosurveys and Vaccine Study Site Preparations

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Patrick Duffy · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $780,824 — LMIV produced and obtained antigens for multiple COVID-19 serology assays. First, plasmids were obtained for production of full-length spike and RBD used in the assay developed by Florian Krammer at Mount Sinai Hospital in New York. After 3 successful production runs of COVID-19 spike proteins used…

The Glycan Shield of the SARS-Cov-2 Spike; Antigenicity and Function

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

JAMES L ARTHOS · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $92,584 — We have produced various versions of a recombinant SARS-CoV-2 Spike glycoproteins that differ in their glycan content. We then characterized the way in which these differentially glycosylated forms of the spike interact with ACE2, and various lectin receptors (e.g L-SIGN, DC-SIGN). In addition, we a…

COVID vaccine-associated allergic reactions

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Pamela Guerrerio · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $35,184 — The SARS-CoV-2 virus has incited a global pandemic leading to profound loss of human life and tremendous economic and social upheaval. In late 2020, the FDA issued emergency use authorizations (EUAs) for mRNA vaccines produced by Pfizer-BioNTech and Moderna that were found to be highly effective in …

Coronavirus vaccine development

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Barney Graham · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $522,460 — When the MERS CoV outbreak raised global health concerns, we initiated a program to develop a candidate vaccine. Based on prior studies to solve the spike structure of HKU1 (an endemic betacoronavirus) and finding stabilizing mutations that also stabilized MERS-CoV and SARS-CoV spike proteins, and p…

Design of Antigenically-Specific Probes for Sera Analysis and MAb Isolation

NIH Pandemic-Era Grants · Pandemic Era Grants / 2021

Tongqing Zhou · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2021 · $157,844 — An understanding of the serum responses of virus-infected individuals and vaccinees is critical for the development of effective vaccines against HIV-1, SARS-CoV-2 and other viral pathogens. Perhaps the most important biological aspect of a serum response is its neutralizing activity, with a close s…