A5014951960- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Protein purification and stability
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- DNA and Nucleic Acid Chemistry
- Advanced Biosensing Techniques and Applications
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- RNA Interference and Gene Delivery
- Growth Hormone and Insulin-like Growth Factors
- Bacteriophages and microbial interactions
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Genetics, Aging, and Longevity in Model Organisms
- Biomedical Text Mining and Ontologies
- Animal Genetics and Reproduction
- Malaria Research and Control
- Complement system in diseases
- Immunotherapy and Immune Responses
- COVID-19 epidemiological studies
St Vincent's Clinic
2012-2025
UNSW Sydney
2012-2025
Garvan Institute of Medical Research
2015-2025
Medical College of Wisconsin
2021
The Kinghorn Cancer Centre
2019
University of California, Berkeley
2017-2018
QB3
2017-2018
Cpf1 is a novel class of CRISPR-Cas DNA endonucleases, with wide range activity across different eukaryotic systems. Yet, the underlying determinants this variability are poorly understood. Here, we demonstrate that LbCpf1, but not AsCpf1, ribonucleoprotein complexes allow efficient mutagenesis in zebrafish and Xenopus. We show temperature modulates by controlling its ability to access genomic DNA. This effect stronger on explaining lower efficiency ectothermic organisms. capitalize property...
Significance Antibodies are selected to bind microbial but not self-antigens, because binding self would compete with microbes, shorten antibody half-life, and cause autoimmunity. Self-tolerance is actively acquired in part by discarding self-binding antibodies before the body exposed a microbe or vaccine. The experiments here provide evidence of an opposite mechanism, allowing that initially both foreign self-antigens acquire self/non-self discrimination during course immune response...
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...
The availability of stable human antibody reagents would be considerable advantage for research, diagnostic, and therapeutic applications. Unfortunately, variable heavy light domains (V H V L ) that mediate the interaction with antigen have propensity to aggregate. Increasing their aggregation resistance in a general manner has proven difficult persistent problem, due high level sequence diversity observed requirement maintain binding. Here we outline such an approach. By using phage display...
CRISPR-Cas RNA-guided endonucleases hold great promise for disrupting or correcting genomic sequences through site-specific DNA cleavage and repair. However, the lack of methods cell- tissue-selective delivery currently limits both research clinical uses these enzymes. We report design in vitro evaluation S. pyogenes Cas9 proteins harboring asialoglycoprotein receptor ligands (ASGPrL). In particular, we demonstrate that resulting ribonucleoproteins (Cas9-ASGPrL RNP) can be engineered to...
Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence antibody titers declining rapidly after infection and reports reinfection. Here, we monitor responses SARS-CoV-2 receptor-binding domain (RBD) for up 6 months infection. While are maintained, ∼13% cohort's neutralizing return background. However, encouragingly, in a selected subset 13 participants, 12 have detectable RBD-specific...
Abstract Emerging variants of concern (VOCs) are threatening to limit the effectiveness SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing strategies for their identification therefore urgently required. Here we demonstrate that can be isolated from peripheral blood mononuclear cells convalescent patients using receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, epitope class 1,...
Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse receptor-binding domains (RBDs) identify targeting of vulnerability. Antibodies broad reactivity clade B RBDs class 4 epitope, recurring IGHV/IGKV pairs, were readily elicited but...
Human VH single domains represent a promising class of antibody fragments with applications as therapeutic modalities. Unfortunately, isolated human also generally display poor biophysical properties and propensity to aggregate. This has encouraged the development non-human alternative means antigen recognition and, in particular, camelid (VHH) domains. Naturally devoid light chain partners, these are characterized by favorable for cleft binding, highly desirable characteristic, allowing...
Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and implications infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in circulating T cell compartment children mild/asymptomatic COVID-19 compared adult household contacts same severity who had more evidence of systemic...
Antibodies against coronavirus spike protein potently protect infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This exemplified by a set of iconic well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, including mAbs m396, CR3022, CR3014 80R, which neutralize SARS-CoV-1, not SARS-CoV-2. Here, we explore antibody engineering strategies change broaden their specificity, enabling nanomolar binding potent...
SUMMARY The continued threat of SARS-CoV-2 to global health necessitates development improved research tools and vaccines. We present an spike ectodomain, “VFLIP”, bearing five proline substitutions, a flexible cleavage site linker, inter-protomer disulfide bond. VFLIP displays significantly stability, high-yield production retains its trimeric state without exogenous trimerization motifs. High-resolution cryo-EM glycan profiling reveal that the quaternary structure glycosylation mimic...
Abstract DNA i-motif structures are formed in the nucleus of human cells and believed to provide critical genomic regulation. While existence has been demonstrated by immunofluorescent staining characterisation select model genes, abundance distribution such genome remained unclear. Here we utilize high affinity immunoprecipitation followed sequencing map i-motifs DNA. Validated biolayer interferometry circular dichroism spectroscopy, our approach identified over 650,000 The widely...
The emergence of SARS-CoV-2 variants concern (VOCs) has greatly diminished the neutralizing activity previously FDA-approved monoclonal antibodies (mAbs), including that antibody cocktails and first-generation broadly such as S309 (Sotrovimab). In contrast, targeting cryptic conformational epitopes receptor binding domain (RBD) have demonstrated broad against emerging variants, but exert only moderate activity, which so far hindered clinical development. Here, we utilize in vitro display...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome highly metastatic KPC (
Merozoite surface protein 2 (MSP2) is an intrinsically disordered, membrane-anchored antigen of the malaria parasite Plasmodium falciparum. MSP2 can elicit a protective, albeit strain-specific, antibody response in humans. Antibodies are generated to conserved N- and C-terminal regions but many these react poorly with native on surface. Here we demonstrate that recognition N-terminal epitope by mAb 6D8 incompatible membrane-bound conformation region, suggesting mechanism which escapes...