10000 documents

Cleaved, stabilized HIV-1 Env trimers for structural and vaccine studies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

JOHN P MOORE · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $3,108,766 — Overall Abstract This HIVRAD Program Project renewal application is made in response to PAR-18-319. It contains two Research Projects, one Scientific Core and an Administrative Core, under the direction of Principal Investigator, John P. Moore, PhD (Weill Cornell Medical College; WCMC) and co-Princi…

Biophysical Mechanisms of Hyperoxia-Induced Lung Injury

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

CHRISTOPHER M WATERS · UNIVERSITY OF KENTUCKY · 2020 · $522,331 — Acute lung injury and its more severe form, acute respiratory distress syndrome (ARDS), are devastating illnesses with high rates of incidence and mortality. Patients with acute lung injury are typically provided supplemental oxygen using positive pressure mechanical ventilation, but this can lead t…

Discovery of Novel Epitopes for Antibody Dependent Cell-mediated Cytotoxicity Against HIV-1 Infected Cells

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Cynthia Ann Derdeyn · EMORY UNIVERSITY · 2020 · $267,750 — Project Summary/Abstract HIV research efforts are strongly focused on developing vaccines that can elicit highly protective antibody responses. There is evidence from human and nonhuman vaccine studies that both neutralizing and non- neutralizing antibody activities contribute to protection against …

Development of a safe and effective RBD-based vaccine against MERS-CoV

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

PETER J HOTEZ · BAYLOR COLLEGE OF MEDICINE · 2020 · $549,181 — Abstract: In response to the NIH's call for countermeasures to prevent emerging infectious diseases, we will develop, test and manufacture the Middle East Respiratory Syndrome Coronavirus receptor binding protein (MERS-CoV RBD) vaccine as an innovative countermeasure. According to the WHO, MERS-CoV …

Glycan dependent epitopes of HIV broadly neutralizing antibodies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

JAMES C PAULSON · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $887,498 — PROJECT SUMMARY/ABSTRACT There is as yet no effective vaccine to HIV despite concerted efforts by numerous groups worldwide to produce one. The target for vaccines is the envelope spike protein (gp120/gp41), which mediates binding to receptors on the surface of CD4 T cells. The problem from a vaccin…

Competition and morphogenesis in tip cell-mediated branching of tubular networks

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

AMIN S GHABRIAL · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $335,807 — Ghabrial – Project Summary To build a functional vascular system, a network of endothelial tubes must be generated through a combination of vasculogenesis and angiogenesis. During sprouting angiogenesis, endothelial tip cells lead the outgrowth of new branches. Tip cells anastomose with other tip ce…

Structural study of the HIV1 gp41 coat protein

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Adriaan Bax · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2020 · $995,227 — The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers an…

Computational Chemistry and Macromolecular Modeling

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

William Copeland · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · 2020 · $472,295 — During this fiscal year we continued to devote major effort to work aimed at applications of molecular dynamics and quantum mechanics/molecular mechanics simulations required to help support the computational chemistry and molecular modeling needs of NIEHS scientists. Some projects involved creatio…

Finding Protein Sequence Motifs--methods And Applications

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Eugene V Koonin · NATIONAL LIBRARY OF MEDICINE · 2020 · $413,126 — The rapid accumulation of genome sequences and protein structures during the last decade has been paralleled by major advances in sequence database search methods. The powerful Position-Specific Iterating BLAST (PSI-BLAST) method developed at the NCBI forms the basis of our work on protein motif ana…

COVID-19 biomarker discovery

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Aleksandra Nita-Lazar · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $5,612 — The focus of the proteomic approach is to identify and quantify viral structural proteins, specifically spike (S) glycoprotein as well as envelope (E) protein, membrane (M) protein, and nucleocapsid (N) protein in patient samples. The S protein mediates attachment of the virus to the host cell surfa…

Recombinant Engineering of SARS-CoV-2 Spike and N proteins

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

David Margulies · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $38,570 — Our goal in this project is to explore published structures of the SARS-CoV-2 Spike protein with a focus on its receptor binding domain (RBD), in efforts to generate recombinant molecules of increased thermal stability. To this end we have examined published structures and bioinformatically have mad…

SARS-CoV-2 Immunology and Therapeutics

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

KIM HASENKRUG · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $72,116 — A primary goal of this project is to understand the basic immunological responses involved in the recovery from COVID-19 using animal models including mice, hamsters and non-human primates. To date we have completed the first phase of testing SARS-CoV-2-infected rhesus macaques that were depleted of…

Human monoclonal antibodies against SARS-CoV-2

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Joshua Hoong Yu Tan · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $3,181,843 — The overarching goal of this project is to study the immune response to COVID-19 at the monoclonal level to increase our understanding of basic biology and develop new tools to combat disease. This project has started recently, so most of our findings are still preliminary. We have screened plasma f…

Development of COVID-19 cell entry inhibitors

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Nadya Tarasova · DIVISION OF BASIC SCIENCES - NCI · 2020 · $303,572 — 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…

Deciphering the Double-Edged Role of IFITM3 during SARS-CoV-2 Infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Alex Compton · DIVISION OF BASIC SCIENCES - NCI · 2020 · $265,660 — We have successfully produced HIV-based pseudovirus bearing the spike protein of SARS-CoV-1 and SARS-CoV-2 and produced cell lines that are permissive to these pseudoviruses. We have developed a protocol for transiently transfecting human ACE2 (the receptor for SARS-CoV-1 and SARS-CoV-2) and TMPRSS2…

Disease Modeling of Influenza and Other Emerging Respiratory Viral Pathogens

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Heinrich Feldmann · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $856,485 — Over the past fiscal year, we have performed studies on four viral pathogens causing respiratory disease in humans, Nipah virus, influenza virus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). From February to July 2020, only…

Cell biology of SARS-CoV-2 infection

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Ted Hackstadt · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $18,479 — We are using cell culture models to study SARS-CoV-2 replication. African Green Monkey Kidney (Vero) cells are being used as a model system to study interactions with the host cell. A time course of viral replication was first evaluated by immunofluorescence and electron microscopy. Using commerci…

Novel SARS-CoV-2 vaccine candidates: Live, recombinant Leishmania

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

David Sacks · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $22,137 — In order to overexpress SARS CoV-2 spike protein (S) in Leishmania, the full length S gene sequence was amplified by PCR from plasmid pCAGGS containing the Wuhan-Hu-1 spike and inserted into plasmid pSSU-NEO using a Gibson Assembly reaction, with the addition of an N-terminal myc tag and a C-termi…

Coronavirus vaccine development

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Barney Graham · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2020 · $1,394,275 — When the MERS CoV outbreak raised global health concerns, we initiated a program to develop a candidate vaccine. Starting from Spike glycoprotein (S) sequences, we developed an immunization strategy consisting of a full-length S DNA prime and a S1 subunit protein boost that elicited high titers of n…

Study the pathogenesis of neurological disorders using human neural cultures derived from patient peripheral blood CD34 cells

NIH Pandemic-Era Grants · Pandemic Era Grants / 2020

Avindra Nath · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · 2020 · $1,054,273 — Specific aim 1: Develop in vitro 3D brain organoid models derived from human adult peripheral CD34+ cells to study neural development and degeneration and infectious diseases involving human brain. We continued to characterize the 3D brain organoids with multiple cell types including neurons, glial …