A5054703904- Aquaculture disease management and microbiota
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- interferon and immune responses
- Immune Response and Inflammation
- Invertebrate Immune Response Mechanisms
- Animal Vocal Communication and Behavior
- Primate Behavior and Ecology
- SARS-CoV-2 and COVID-19 Research
- Animal Behavior and Reproduction
- Erythrocyte Function and Pathophysiology
- Ichthyology and Marine Biology
- Atherosclerosis and Cardiovascular Diseases
- Immunotherapy and Immune Responses
- Genomics and Phylogenetic Studies
- Protein purification and stability
- Complement system in diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Hemoglobin structure and function
- Animal Virus Infections Studies
- Identification and Quantification in Food
- SARS-CoV-2 detection and testing
University of Maryland, Baltimore
2010-2024
Institut de Ciències del Mar
2022
Footscray Hospital
2019
University of Aberdeen
1998-2019
The University of Western Australia
2007-2014
Pfizer (United Kingdom)
2011-2013
Pfizer (United States)
2011
Scripps Research Institute
2004
National Aquarium
2004
Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of vertebrate adaptive immune system. Key their response heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which variable (V) domains recognize antigens with only a single immunoglobulin domain, akin camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure type I IgNAR domain complex hen egg-white lysozyme (HEL) reveals minimal antigen-binding...
Despite rapid and ongoing vaccine therapeutic development, SARS-CoV-2 continues to evolve evade, presenting a need for next-generation diverse modalities. Here we show that nurse sharks immunized with recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit set of new antigen antibody (IgNAR) molecules target two non-overlapping conserved epitopes on the RBD. Representative shark variable NAR-Fc chimeras (ShAbs) targeting...
The cartilaginous fish are the oldest phylogenetic group in which all of molecular components adaptive immune system have been found. Although early studies clearly showed that sharks could produce an IgM-based response following immunization, evidence for memory, affinity maturation and roles other isotypes (notably IgNAR) this remained inconclusive. data presented here illustrate nurse shark (Ginglymostoma cirratum) is able to not only IgM response, but we also show first time a highly...
Interferons orchestrate host antiviral responses in jawed vertebrates. They are categorized into three classes; IFN1 and IFN3 the primary cytokine lineages, while IFN2 responds to a broader variety of pathogens. The evolutionary relationships within between these classes have proven difficult resolve. Here, we reassess interferon evolution, considering key phylogenetic pitfalls including taxon sampling, alignment quality, model adequacy, outgroup choice. We reveal that cartilaginous fishes,...
The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the types present shark spleen, RNAscope provide situ cellular resolution key marker gene expression following immunization R-phycoerythrin (PE). We tracked PE splenic follicles...
The cartilaginous fish are the oldest phylogenetic group in which Igs have been found. Sharks produce a unique Ig isotype, IgNAR, heavy-chain homodimer that does not associate with light chains. Instead, variable (V) regions of IgNAR bind antigen as soluble single domains. Our has shown plays an integral part humoral response nurse sharks ( Ginglymostoma cirratum ) upon challenge. Here, we generated phage-displayed libraries V from immunized animal and found family clones derived same...
Chondrichthyes (cartilaginous fishes) are fundamental for understanding vertebrate evolution, yet their genomes understudied. We report long-read sequencing of the whale shark genome to generate best gapless chondrichthyan assembly with higher contig contiguity than all other cartilaginous fish genomes, and studied genomic evolution ancestral gene families, immunity, gigantism. found a major increase in families at origin gnathostomes (jawed vertebrates) independent duplication. pathogen...
Adult cartilaginous fish express three immunoglobulin (Ig) isotypes, IgM, IgNAR and IgW. Newborn nurse sharks, Ginglymostoma cirratum, produce 19S (multimeric) IgM monomeric/dimeric IgM1gj, a germline-joined, IgM-related VH, very low amounts of 7S (monomeric) proteins. VH mRNAs are diverse in the complementarity-determining region 3 (CDR3) with non-templated nucleotide (N-region) addition, which suggests that, unlike many other vertebrates, terminal deoxynucleotidyl transferase (TdT)...
B-lymphocyte-induced maturation protein 1 (Blimp-1) is the master regulator of plasma cell development, controlling genes such as those encoding J-chain and secretory Ig heavy chain. However, some mammalian cells do not express J-chain, B1 secrete "natural" IgM antibodies without upregulating Blimp-1. While these results have been controversial in systems, here we describe subsets normally occurring Blimp-1(-) antibody-secreting nurse sharks, found lymphoid tissues at all ontogenic stages....
The cartilaginous fishes diverged from other jawed vertebrates ~ 450 million years ago (mya). Despite this key evolutionary position, the only high-quality fish genome available is for elephant shark (Callorhinchus milii), a chimaera whose ancestors split elasmobranch lineage 420 mya. Initial analysis of resource led to proposals that components adaptive immune system, most notably their array T cell subsets, was primitive compared mammals. This proposal at odds with robust, antigen-specific...
Antibody fragments have the potential to be used as sensitive and specific binding agents in a broad range of industrial applications. Genetic manipulation has been design series antibody fragment configurations with flexible linker and/or disulphide bond between heavy chain light an against herbicide atrazine. The thermostability stability denaturants, polar non-polar solvents, surfactants proteases compared. It found that novel construct (STAB: stabilized antibody) containing both can...
As of 8 August 2022, SARS-CoV-2, the causative agent COVID-19, has infected over 585 million people and resulted in more than 6.42 deaths worldwide. While approved SARS-CoV-2 spike (S) protein-based vaccines induce robust seroconversion most individuals, dramatically reducing disease severity risk hospitalization, poorer responses are observed aged, immunocompromised individuals patients with certain pre-existing health conditions. Further, it is difficult to predict protection conferred...