A5065406786- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Protein Structure and Dynamics
- Hemoglobin structure and function
- Monoclonal and Polyclonal Antibodies Research
- Evolution and Genetic Dynamics
- Neonatal Health and Biochemistry
- RNA and protein synthesis mechanisms
- vaccines and immunoinformatics approaches
- Respiratory viral infections research
- Erythrocyte Function and Pathophysiology
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- Hemoglobinopathies and Related Disorders
- Genetic Neurodegenerative Diseases
- COVID-19 Clinical Research Studies
- DNA Repair Mechanisms
- Neuroethics, Human Enhancement, Biomedical Innovations
- PARP inhibition in cancer therapy
- Regulation of Appetite and Obesity
- Bacillus and Francisella bacterial research
- Click Chemistry and Applications
- Photosynthetic Processes and Mechanisms
- Viral Infections and Immunology Research
University of Illinois Urbana-Champaign
2021-2024
University of Electronic Science and Technology of China
2024
Florida International University
2017-2022
Nanjing Agricultural University
2013
Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All vaccines in US encode with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering immunogens involve tedious experimental work and heavily rely structural information. Here, we establish a systematic unbiased method identifying that concomitantly improve expression conformation spike. Our integrates fluorescence-based fusion assay,...
Antigenic drift of SARS-CoV-2 is typically defined by mutations in the N-terminal domain and receptor binding spike protein. In contrast, whether antigenic occurs S2 remains largely elusive. Here, we perform a deep mutational scanning experiment to identify that affect three apex public antibodies. Our results indicate spatially diverse mutations, including D950N Q954H, which are observed Delta Omicron variants, respectively, weaken these Although antibodies known be nonneutralizing, show...
Abstract The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane during virus entry and part a broadly neutralizing epitope. However, sequence determinants at the its adjacent regions pathogenicity antigenicity remain elusive. In this study, we perform series deep mutational scanning (DMS) experiments on an S2 region spanning authentic in different cell lines presence antibodies. We identify mutations residue 813 that reduced TMPRSS2-mediated with decreased...
Abstract The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D D190N in the have coevolved two recent human H3N2 clades. X-ray crystallography results show these coordinately drive evolution receptor binding mode. Epistasis between is further demonstrated by glycan thermostability analyses. Immunization neutralization experiments using mouse samples indicate mode...
As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA recently emerged as an effective vaccine target, biophysical constraints on antigenic evolution remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing characterize local fitness landscape region six different human strains that were isolated around 10 apart. The correlates well among...
Increasing the expression level of SARS-CoV-2 spike (S) protein has been critical for COVID-19 vaccine development. While previous efforts largely focused on engineering receptor-binding domain (RBD) and S2 subunit, amino-terminal (NTD) long overlooked because limited understanding its biophysical constraints. In this study, effects thousands NTD single mutations S were quantified by deep mutational scanning. Our results revealed that in terms expression, tolerability residues was inversely...
Influenza neuraminidase (NA) has received increasing attention as an effective vaccine target. However, its mutational tolerance is not well characterized. Here, the fitness effects of >6,000 mutations in human H3N2 NA are probed using deep scanning. Our result shows that while antigenic regions have high tolerance, there solvent-exposed with low tolerance. We also find protein stability a major determinant fitness. The scanning correlates inferred from natural sequences language model,...
Immune imprinting is a driver known to shape the anti-hemagglutinin (HA) antibody landscape of individuals born within same birth cohort. With HA and neuraminidase (NA) proteins evolving at different rates under immune selection pressures, anti-HA anti-NA responses since childhood influenza virus infections have not been evaluated in parallel individual level. This partly due limited knowledge changes NA antigenicity, as seasonal vaccines focused on generating neutralizing antibodies against...
The Cu(I)- or Ag(I)-catalyzed cycloaddition between 8-ethynyladenine guanine nucleosides and TMSN3 gave 8-(1-H-1,2,3-triazol-4-yl) in good yields. On the other hand, reactions of 5-ethynyluracil cytosine with led to chemoselective formation triazoles via Cu(I)-catalyzed vinyl azides hydroazidation. These a minimalistic triazolyl modification showed excellent fluorescent properties 8-(1-H-1,2,3-triazol-4-yl)-2′-deoxyadenosine (8-TrzdA), exhibiting quantum yield 44%. 8-TrzdA 5′-triphosphate...
Despite decades of antibody research, it remains challenging to predict the specificity an solely based on its sequence. Two major obstacles are lack appropriate models and inaccessibility datasets for model training. In this study, we curated a dataset >5,000 influenza hemagglutinin (HA) antibodies by mining research publications patents, which revealed many distinct sequence features between HA head stem domains. We then leveraged develop lightweight memory B cell language (mBLM)...
This paper will focus on analyzing the argument with appealing to nature against synthetic biology and provide a counter-argument it through demonstrating ambiguity of concept nature, denying existence morally significant line between natural non/unnatural, disproving allegations raised by nature. The consists two parts following brief introduction. first part describe biology, identify deficiencies per se , e.g., ‘nature’; problems in non/unnatural. second discuss stemming from this...
Abstract Here, we report the preparation and photo-physical characterization of hexa-coordinated vertebrate globins, human neuroglobin (hNgb) cytoglobin (hCygb), with native iron protoporphyrin IX (FePPIX) cofactor replaced by a fluorescent isostructural analogue, zinc (ZnPPIX). To facilitate insertion ZnPPIX into apoproteins prepared via butanone extraction were unfolded addition GuHCl subsequently slowly refolded in presence ZnPPIX. The absorption/emission spectra reconstituted hCygb are...
Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All vaccines in US encode with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering immunogens involve tedious experimental work and heavily rely structural information. Here, we established a systematic unbiased method identifying that concomitantly improve expression conformation spike. Our integrated fluorescence-based fusion assay,...
Abstract Neuraminidase (NA) of human influenza H3N2 virus has evolved rapidly and been accumulating mutations for more than half-century. However, biophysical constraints that govern the evolutionary trajectories NA remain largely elusive. Here, we show among 70 natural are present in a recent strain, >10% deleterious an ancestral strain. By mapping permissive using combinatorial mutagenesis next-generation sequencing, extensive epistatic network is revealed. Biophysical structural...
IGHV1-69 is frequently utilized by broadly neutralizing influenza antibodies to the hemagglutinin (HA) stem. These HA stem have diverse complementarity-determining region (CDR) H3 sequences. Besides, their light chains minimal no contact with epitope. Consequently, sequence determinants that confer specificity remain largely elusive. Using high-throughput experiments, this study reveals importance of light-chain for antibody CR9114, which broadest known date. Moreover, we demonstrate CDR...
Trinucleotide repeat (TNR) instability is associated with human neurodegenerative diseases and cancer. Recent studies have pointed out that DNA base excision repair (BER) mediated by polymerase β (pol β) plays a crucial role in governing somatic TNR damage-location dependent manner. It has been shown the activities function of BER enzymes cofactors can be modulated their polymorphic variations. This could alter regulating instability. However, roles polymorphism modulating remain to...
Abstract The authors argue that in preventing and controlling the pandemic of Covid‐19, we should have taken an offensive or proactive strategy rather than a defensive reactionary one because former type approach can bring about more health benefits fewer harms latter. consists two parts: first part is to preemptively establish barrier between novel virus humans order prevent spillover into humans, second that, when fails be prevented, take public interventions, such as contact tracing,...
ABSTRACT Increasing the expression level of SARS-CoV-2 spike (S) protein has been critical for COVID-19 vaccine development. While previous efforts largely focused on engineering receptor-binding domain (RBD) and S2 subunit, N-terminal (NTD) long overlooked due to limited understanding its biophysical constraints. In this study, effects thousands NTD single mutations S were quantified by deep mutational scanning. Our results revealed that in terms expression, tolerability residues was...
Antibody discovery is crucial for developing therapeutics and vaccines as well understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents major bottleneck antibody discovery. Here, we presented oPool + display, cell-free platform that combined oligo pool synthesis mRNA display rapidly construct characterize many natively paired parallel. As proof-of-concept, applied probe binding specificity >300...