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9873 documents

Research and Development to Establish a Small Animal Model as a Significant Resource of High-Value Single-Domain Antibodies

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Milen Kirilov · INGENIOUS TARGETING LABORATORY, INC. · 2023 · $995,450 — Project Summary Genetically-modified mouse models have proven to be essential for the production of antibody-related biological drugs (biologics). To date, the majority of biologics originate from mouse models, and small animal models are used not only to generate the antibodies, but also as a platf…

Data Management for Molecule Simulation : A Throughput-Oriented Approach

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Yicheng Tu · UNIVERSITY OF SOUTH FLORIDA · 2023 · $285,048 — Project Summary We will design and develop a molecular simulation data management system, we call P2DMS, to analyze large dis- tributed molecular dynamics (MD) simulation data. The salient features of the system include: (1) a push-based local query engine design that handles data in a batch process…

Broadly neutralizing SARS-CoV-2 peptidic knobs

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Vaughn Vasil Smider · APPLIED BIOMEDICAL SCIENCE INSTITUTE · 2023 · $967,225 — Abstract Targeted therapeutic agents range in size from very small organic molecules (100’s of Da) to protein-based molecules like monoclonal antibodies (~150,000 Da). Small disulfide bonded peptides have evolved in many species, including plants and animals, to have ideal pharmacological properties…

Modeling Neurofibromatosis Type 2 with Inner Ear Organoids

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Matthew Reed Steinhart · INDIANA UNIVERSITY INDIANAPOLIS · 2023 · $55,194 — ABSTRACT Neurofibromatosis Type 2 (NF2) is a genetic condition in which specific types of tumors form in various locations throughout the body. Though the majority of these tumors grow slowly, the location of certain tumors can cause significant dysfunction. One of these tumor types grows on the ves…

Improving mRNA vaccines with extracellular vesicle-associated immunogens

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Michael R. Farzan · UNIVERSITY OF FLORIDA · 2023 · $82,817 — Abstract The central hypothesis of this proposal is that the efficacy of mRNA vaccines that deliver membrane-anchored immunogens can be improved by localizing the immunogen to extracellular vesicles (EVs, small membrane- limited structures shed by eukaryotic cells). Our rationale is that EVs provide…

Structural interrogation of vaccine- and infection-induced B cell responses

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Goran Bajic · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2023 · $782,700 — Immunodominance, the observation that epitopes on an antigen are not “born equal”, poses a major challenge for next-generation vaccines against rapidly evolving pathogens. An underlying premise of this proposal is that in order to engage in rational immunogen design for next-generation vaccines, we …

COVID-19 airway inflammation is due to Spike inhibition of CFTR signaling

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Harvey Bruce Pollard · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2023 · $663,601 — Abstract Over 860,000 COVID-19 deaths have occurred in the U.S., and more than 5.5 million deaths have occurred world-wide. Consequently, development of effective antiviral drugs that block infectivity and airway inflammation continue to be a global health priority. Inflammation in the COVID-19 air…

Proteomics-Driven Reverse Vaccinology for Gonorrhea

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Aleksandra Elzbieta Sikora · OREGON STATE UNIVERSITY · 2023 · $719,450 — ABSTRACT Neisseria gonorrhoeae (Ng), the gram-negative bacterium responsible for the sexually transmitted infection gonorrhea, is categorized as a high-priority pathogen for research and development efforts. In the US, over 50% of Ng isolates are resistant to at least one antimicrobial and the CDC h…

Comprehensive genomic and inflammatory profiling of vaccine-associated myocarditis

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Amy R. Kontorovich · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2023 · $253,500 — PROJECT SUMMARY The cardiac inflammatory disorder myocarditis is a rare but important complication following vaccination against COVID-19. Other than younger age and male sex, no risk factors for this adverse outcome have been found. Recognition of host factors that predispose to vaccine-associated …

Entry inhibition of SARS-CoV-2 by human LRRC15

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Sanghyun Lee · BROWN UNIVERSITY · 2023 · $217,338 — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 19 (COVID-19), representing a global health threat. The viral spike protein, anchored on the surface of the viral envelope as homotrimers, binds to angiotensin-converting enzyme 2 (ACE2) and me…

Mechanism of myosin motor-dependent filopodia formation

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

MARGARET A TITUS · UNIVERSITY OF MINNESOTA · 2023 · $14,187 — Abstract of Parent Project Cells migrating in tissues, including cancer cells, use filopodia to guide them through the 3D environment and increased formation of filopodia correlates strongly with the metastatic potential and invasiveness of cancer cells. Filopodia are slender actin-filled projectio…

Covid-19: Fast-tracking treatment by exploiting the steroid hormone receptor/TMPRSS2 axis

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Kerry L Burnstein · MIAMI VA HEALTH CARE SYSTEM · 2023 — COVID-19 poses a tremendous health threat, particularly to individuals overrepresented in the US Veteran community. COVID-19 mortality is greater in men than in women; while this disparity is at least partially due to factors such as higher rates of smoking, a hormonal link is likely and can be rapi…

CoVPN 3001

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Dan H. Barouch · FRED HUTCHINSON CANCER CENTER · 2023 · $305,278 — This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for continuing implementation of the first COVID-19 vaccine efficacy trial “A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the…

Rapid response for pandemics: single cell sequencing and deep learning to predict antibody sequences against an emerging antigen

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Jeniffer Bertha Hernandez · KECK GRADUATE INST OF APPLIED LIFE SCIS · 2023 · $1,219,945 — ABSTRACT One of the “holy grails” in immunology is to be able to directly predict tight-binding variable chain antibody sequences in silico against foreign or non-self `antigenic' proteins. Immunoglobulin chain rearrangement can potentially encode approximately 1016 different variants of antibody he…

Improving mRNA vaccines with extracellular vesicle-associated immunogens

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Michael R. Farzan · BOSTON CHILDREN'S HOSPITAL · 2023 · $189,627 — Abstract The central hypothesis of this proposal is that the efficacy of mRNA vaccines that deliver membrane-anchored immunogens can be improved by localizing the immunogen to extracellular vesicles (EVs, small membrane- limited structures shed by eukaryotic cells). Our rationale is that EVs provide…

Multi-color optical voltage imaging of neural activity in behaving animals

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

MARK J SCHNITZER · STANFORD UNIVERSITY · 2023 · $889,939 — Abstract Groundbreaking work within the NIH BRAIN Initiative has revealed many new types of neurons and their genetic signatures. The dividends from this research will include sophisticated tools allowing selective genetic access to these cell-types, such as for imaging, optogenetic or tracing studi…

Initiation of immune responses to SARS COV2 in the oral cavity and upper airway

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

GILL DIAMOND · UNIVERSITY OF MISSISSIPPI MED CTR · 2023 · $1 — Abstract Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a life-threatening illness with multi-system involvement in a subset of infected individuals. Oral and nasopharyngeal (NP) epithelial cells express the SARS-CoV-2 receptor…

Software for the complete characterization of antibody repertoires: from germline and mRNA sequence assembly to deep learning predictions of their protein structures and targets

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

FREDERICK R BLATTNER · DNASTAR, INC. · 2023 · $648,790 — The B cell population in each individual produces an estimated 1010 different antibodies, collectively known as the antibody repertoire. This extraordinary diversity is essential for responding to the unique history of infections, vaccinations and cancer encountered over an individual’s lifetime. Co…

The role of non-canonical neural codes in behavior

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

Masashi Tabuchi · CASE WESTERN RESERVE UNIVERSITY · 2023 · $250,000 — Project Summary/Abstract (Unchanged from the funded parent award) The idea that information processing depends on neuronal firing rate (rate coding) has long been a central dogma in neurobiology. However, other non-canonical coding schemes (temporal and “analog” codes) have been proposed to carry me…

COVID-19: SARS-CoV-2 Neutralizing Agents

NIH Pandemic-Era Grants · Pandemic Era Grants / 2023

SUBHRA MOHAPATRA · JAMES A. HALEY VA MEDICAL CENTER · 2023 — COVID-19 super pandemic is still suffering from the lack of a vaccine or infection control measures and the lack of any treatments against this new virus. One of the unique features of SARS-CoV-2 is that it has an R0=2.2 (the ability of an infected patient to spread the disease) vs R0=1 for SARS-CoV…