10000 documents

High throughput antibody discovery against cell membrane bound target proteins using innovative MOD technology for direct screening in single-cell assays

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Russell H Cole · SCRIBE BIOSCIENCES, INC. · 2023 · $300,000 — ABSTRACT Scribe Biosciences are leading experts in the field of droplet microfluidics and have developed a best-in-class droplet manipulation platform, Microenvironment on Demand (MOD), that can currently assemble >100k paired-cell assays in <3 hours, with proven proof of concept. Using this innovat…

Physics-based characterization of functionally relevant protein conformational dynamics

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Mahmoud Moradi · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · 2023 · $364,879 — PROJECT SUMMARY With recent advances in structural biology and supercomputing technology, all-atom molecular dynamics (MD) simulation technique has gained momentum as a prominent tool for the study of protein structural dynamics. Brute-force MD, however, is not capable of adequately sampling most fu…

Structural study of the HIV1 gp41 coat protein

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Adriaan Bax · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2023 · $1,513,712 — The envelope glycoprotein gp41 of the HIV-1 virus mediates its entry into the host cell. During this process, gp41 undergoes large conformational changes and the energy released in the remodeling events is utilized to overcome the barrier associated with fusing the viral and host membranes. Although…

Pattern Identification in Sequence Activity Data

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Vipul Periwal · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2023 · $339,647 — Current models for inferring co-evolutionary contacts from aligned protein sequence data use the principle of maximum-entropy (ME) which assumes that the sequences are in a state of equilibrium with respect to the evolutionary forces acting on them. This has two obvious issues. Firstly, HIV protein …

The role of conformational dynamics of enveloped virus spike proteins in cell entry

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Maolin Lu · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · 2023 · $372,500 — Research Abstract: The spike/fusion glycoproteins residing on the surface of human enveloped viruses are targets of immune response and are the focus of researchers developing vaccines and antiviral treatments. The conformational dynamics of spike proteins drive the entry of enveloped viruses into c…

Combining Molecular Simulations and Biophysical Methods to Characterize Conformational Dynamics of the HIV-1 Envelope Glycoprotein

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

CAMERON F ABRAMS · DREXEL UNIVERSITY · 2023 · $825,050 — PROJECT SUMMARY The HIV-1 envelope glycoprotein spike (Env) mediates viral entry into target cells. Because Env is the only viral protein on the virion surface, it is central to the development of potential vaccines and small-molecule entry inhibitors. Env is a uniquely flexible molecular machine, a…

Pathogenesis, Treatment and Prevention of Emerging Infectious Diseases

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

H. Clifford Lane · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $120,019 — 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…

Paramyxoviruses as Vaccine Vectors Against Highly Pathogenic Viruses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Ursula Buchholz · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $107,577 — 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…

SARS-CoV2 Immunity and Cell Biology

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Jonathan W Yewdell · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $301,514 — We have generated Sleeping Beauty transposase vectors that drive expression of the SARS-CoV-2 receptor ACE2 and or protease TMPRSS2 in host cells and use these vectors to create permanent transfected lines of A549, 293FT, and BHK-21 cells. We have generated a recombinant vesicular stomatitis virus t…

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

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Matthew Hall · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2023 · $2,626,150 — During this past reporting period, NCATS worked towards completing a number of SARS-CoV-2 assays, including target-based and live virus assays, to screen for potential hits against SARS-CoV-2. Optimized assays were screened against a panel of drug repurposing, clinical candidate and antiviral librar…

Neurodifferentiation/Stem Cell Unit

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

David Wang · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · 2023 · $895,783 — Specific aim 1: To develop in vitro 2D neuronal and 3D brain organoid models derived from human adult peripheral CD34+ cells to study neural development and degeneration and infectious diseases involving human brain. We set up a new brain-on-the-chip microfluidic culture equipment into our unit, we…

Scanning Probe Microscopy for the Intramural Research Community

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

EMILIOS K Dimitriadis · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · 2023 · $5,358,669 — Several of the collaborative projects carried over and continued from the previous year. New collaborations were initiated with NIDCR (Ten Hagen lab) and NCI (Rudloff lab). Our NCI collaborations with the Dalal Lab continued with further efforts to investigate the source of chromosome fragility upo…

Production Of HIV And HIV Related Proteins For Structural Studies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

PAUL T WINGFIELD · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · 2023 · $1,484,352 — In uninfected cells, RNA is transcribed from DNA, processed, and then transported out of the nucleus and translated into protein. In cells infected with HIV-1, the viral RNA genomes must be exported out of the nucleus without being processed so they can be packaged into new viral particles. To do th…

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

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Alex Compton · DIVISION OF BASIC SCIENCES - NCI · 2023 · $111,969 — We have successfully produced HIV-based and VSV-based pseudovirus bearing the spike protein of SARS-CoV-1 and SARS-CoV-2 variants 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 …

Structural vaccinology for infectious diseases

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Niraj Tolia · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $723,116 — Malaria is caused by eukaryotic parasites that display distinct surface antigens during three independent stages of the life cycle: 1) initial infection caused by the pre-erythrocytic stage, 2) clinical symptoms as a result of the blood stage, and 3) transmission by the mosquito stage. While both T-…

Countermeasures against COVID-19

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Andrea Marzi · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $222,715 — 1. Intranasal single-dose vaccination with VSV-based COVID-19 vaccines protects rodents from disease We designed, cloned, and recovered two replication-competent VSV-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the EBOV GP (VSV-SARS2-EBOV). EB…

Structural Biology and Biochemistry of Coronavirus

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Audray Harris · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · 2023 · $5,807 — Coronaviruses remain both a seasonal health burden and pandemic threat due to the antigenic variation of viral glycoproteins and the ability of animal coronaviruses to cause zoonotic infections in humans. Although conserved epitopes have been identified, there is a fundamental gap in understanding a…

Transgenic Resources for Neuroscience Research

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Susan Amara · NATIONAL INSTITUTE OF MENTAL HEALTH · 2023 · $1,496,655 — 1) Production of rodent transgenics Mouse transgenic production projects: 12 Rat transgenic production projects: 2 Cryopreservation projects: 35 Rederivation projects: 23 2) SARS-Cov2 Fibroblast cultures have been propagated using methods developed in the lab (see below) over several years. These c…

Inhibitors and Probes of HIV-1 Cell Fusion

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Carole Bewley · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · 2023 · $947,627 — The long term goals and objectives of our project "Inhibitors and Probes of HIV-1 Cell Fusion" are to identify and engineer protein and small molecule therapeutics, probes and vaccine immunogens that can be translated for the treatment and long acting inhibition of HIV/AIDS. Subprojects include desi…

Antibody discovery

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Anton Simeonov · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · 2023 · $125,849 — The antibody discovery project harnesses the therapeutic potential of small biologicals known as nanobodies. By constructing a humanized llama phage display library for use here at NCATS, it is possible to screen for therapeutically relevant nanobodies as needed. The small size of nanobodies makes t…