Biology subjects

Buckley, J.

Publications and source records attributed to Buckley, J..

6 recordsLinked to original sources

bioRxiv2025

The 1000+ mouse project: large-scale spatiotemporal parametrization and modeling of preclinical cancer immunotherapies

Preclinical studies of chimeric antigen receptor (CAR)-T cell immunotherapies are often based on monitoring bioluminescent tumors implanted in mice to assess anti-tumor cytotoxicity. Here, we introduce maRQup (murine automatic Radiance Quantification and parametrization), an easy-to-use method that automatically processes bioluminescent tumor images for quantitative analysis. We demonstrate the ability of maRQup to analyze CAR-T cell treatments over >1,000 tumor-bearing mice. We compare CD19-targeting CAR-T cells comprising either a CD28 or a 4-1BB costimulatory domain, and found the former controlled the tumor burden better initially, while the latter reduced the frequency of tumor relapse. We also applied maRQup to demonstrate faster tumor growth during the initial growth phase as compared to the relapse phase and to spatiotemporally analyze the high variability in immunotherapeutic control of tumors, based on their anatomical location. maRQup provides quantitative and statistically-robust insights on preclinical experiments that will contribute to the optimization of immunotherapies.

immunology↗

bioRxiv2022

The Role of Glycocalyx Steric Effects on Viral Endocytosis

Understanding the mechanisms of viral entry is key to aiding the development of effective anti-viral treatments. In this work, we produce a simple thermodynamic model of viral entry, which is able to predict the differences between viruses. We also show that the glycocalyx, which is often neglected in studies of cell-entry, plays a key role, and the density and structure of the glycocalyx can determine whether or not a virus can enter the cell. We further find that co-receptors play not only a signalling role, but an important thermodynamic role in viral entry. We then show that this model can be used to calculate the cell-entry probabilities of a given virus, which can shine a light on the clinical observations associated with a virus.

biophysics↗

bioRxiv2021

The role of host cell glycans on virus infectivity: The SARS-CoV-2 case

Long and complex chains of sugars, called glycans, often coat both the cell and protein surface. Glycans both modulate specific interactions and protect cells. On the cell surface, these sugars form a cushion known as the glycocalyx. Here, we show that Heparan Sulfate (HS) chains - part of the glycocalyx - and other glycans - expressed on the surface of both host and virus proteins - have a critical role in modulating both attractive and repulsive potentials during viral infection. We analyse the SARS-CoV-2 virus, modelling its spike proteins binding to HS chains and two key entry receptors, ACE2 and TMPRSS2. We include the volume exclusion effect imposed on the HS chains impose during virus insertion into glycocalyx and the steric repulsion caused by changes in the conformation of the ACE2 glycans involved in binding to the spike. We then combine all these interactions, showing that the interplay of all these components is critical to the behaviour of the virus. We show that the virus tropism depends on the combinatorial expression of both HS chains and receptors. Finally, we demonstrate that when both HS chains and entry receptors express at high density, steric effects dominate the interaction, preventing infection.

biophysics↗

bioRxiv2019

Changing environments and genetic variation: inbreeding does not compromise short-term physiological responses

O_LISelfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce long-term evolutionary potential. However, short-term capacity to respond appropriately to new conditions might not require high levels of standing genetic variation. The purpose of this study was to directly test whether mating system variation and its associated changes in genetic variability in natural populations affected responses to short-term environmental challenges.\nC_LIO_LIWe compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a long-lived perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range.\nC_LIO_LIWe found no effect of mating system on survival or reproductive output, although several phenological traits showed different associations with latitude for outcrossing and inbreeding populations. Natural inbreeding had no effect on the plasticity of physiological responses, using either multivariate approaches or analysis of variation in individual metabolites. Moreover, while both growing environment and time significantly affected the relative abundance of individual metabolites, inbreeding populations responded similarly to outbreeding populations, suggesting adaptation to the outdoor environment, regardless of mating system.\nC_LIO_LIWe conclude that low genetic diversity in naturally inbred populations may not compromise fitness or short-term capacity for appropriate physiological responses to environmental change. The absence of natural costs of inbreeding could help to explain the global success of clonal or asexual mating strategies for adapting to a wide range of environments.\nC_LI

evolutionary biology↗

bioRxiv2018

Point of care influenza testing using Alere-i Influenza A & B assay: a practical assessment

We assessed the utility of the Alere i Influenza A & B point of care influenza test (Ai-POCIT) with laboratory testing using RT-PCR. 270 adult hospital patients had both Ai-POCIT and laboratory influenza tests conducted on the same sample. Overall, 30% and 32% influenza tests were positive by Ai-POCIT and RT-PCR, respectively. The sensitivity of the Ai-POCIT for influenza A, influenza B and any influenza were 93%, 100%, and 95%, respectively. Specificity was 100% for both viruses, but an 11% test failure rate indicates the need for better training of users. We believe that the use of nasopharyngeal (NP) swabs resulted in the observed high performance of the Ai-POCIT in comparison to other published studies. Ai-POCIT was regarded as very useful by front line clinical staff for clinical decision making and acute bed management.

microbiology↗

bioRxiv2018

Working memory availability affects neural indices of distractor processing during visual search

Working memory and selective attention are traditionally viewed as distinct processes in human cognition. However, increasing research demonstrates significant overlap between these constructs such that as working memory availability decreases, individuals perform worse on attention-based tasks. To date, the neural mechanisms involved in this interaction are unknown. We measured three candidate lateralized event-related potential components (N2pc, Ptc, and SPCN) to observe the effects of increased working memory load on selective processing of targets and distractors. We found that increased working memory load impaired the processing of distractors, but not targets, and this was reflected in attentuation of the Ptc to distractors. We also found that individual performance on the task is related to the neural response to both targets and distractors. This study suggests that working memory availability impacts individuals ability to disengage from irrelevant stimuli, and that individual differences in visual search ability under load are related to both target and distractor processing.

neuroscience↗