Biology subjects

Cooper, O.

Publications and source records attributed to Cooper, O..

3 recordsLinked to original sources

bioRxiv2026

GPNMB and glycosphingolipid measurements in cerebrospinal fluid and plasma from Parkinson's disease patients in the BioFind cohort

BackgroundParkinsons disease (PD) is a prevalent neurodegenerative disorder characterized by progressive motor dysfunction and broad cellular impairment, including significant disruptions in lysosomal function, lipid metabolism, and intracellular trafficking. Glycosphingolipids (GSLs), critical for various cellular processes, depend on effective lysosomal degradation. Aberrant GSL metabolism has been linked to PD pathology, and glycoprotein non-metastatic melanoma protein B (GPNMB) has emerged as a biomarker associated with lysosomal dysfunction and lipid imbalance in PD ObjectivesTo assess the relationship between GPNMB and GSL levels in cerebrospinal fluid (CSF) and plasma from PD patients and controls within the BioFIND cohort. We also investigated potential sex differences and associations with PD-related biomarkers such as -synuclein MethodsGSL species and GPNMB protein levels were quantified using high-performance liquid chromatography (HPLC) and ELISA assays, respectively, in matched CSF and plasma samples from PD patients and controls ResultsLevels of the paraglobosides GSL species, alpha-2,3SpG and pGb were significantly elevated in the plasma of PD patients compared to healthy controls, while levels of the ganglioside GD1a and the lacto-series GSL, Leb combined (GD1a + Leb), were significantly reduced in PD. GPNMB levels positively correlated with several GSL species in both plasma and CSF. Plasma GSLs and GPNMB concentrations were significantly higher in females compared to males, independent of PD diagnosis. CSF GPNMB correlated positively with age and -synuclein concentrations InterpretationOur findings confirm that GSL metabolism is altered in PD. They also highlight significant sex-based biochemical variations in GSL and GPNMB levels, emphasizing the need for sex-specific analyses in PD biomarker research. The relationship between GSLs and GPNMB supports their potential as interconnected biomarkers of lipid pathology in PD.

neuroscience↗

bioRxiv2023

Identification of Lactuca sativa transcription factors impacting resistance to Botrytis cinerea through predictive network inference

Lettuce is susceptible to a wide range of plant pathogens including the fungal pathogens Botrytis cinerea and Sclerotinia sclerotiorum, causal agents of grey mould and lettuce drop, respectively. Chemical control is routinely used but there is an urgent need to develop varieties with enhanced resistance given the economic and environmental costs of preventative pesticide sprays, the prevalence of fungicide-resistant isolates of both pathogens in the field, and the increasing withdrawal of approved fungicides through legislation. Resistance against Botrytis cinerea and Sclerotinia sclerotiorum is quantitative, governed by multiple small-medium impact loci, with plant responses involving large-scale transcriptional reprogramming. The elucidation of the gene regulatory networks (GRNs) mediating these responses will not only identify key transcriptional regulators but also interactions between regulators and show how the defence response is fine-tuned to a particular pathogen. We generated high-resolution (14 time points) time series expression data from lettuce leaves following mock-inoculation or inoculation with B. cinerea, capturing the dynamics of the transcriptional response to infection. Integrating this data with a time series dataset from S. sclerotiorum infection of lettuce identified a core set of 4362 genes similarly differentially expressed in response to both pathogens. Using the expression data for these core genes (with additional single time point data from 21 different lettuce accessions) we inferred a GRN underlying the lettuce defence response to these pathogens. Using the GRN, we have predicted and validated key regulators of lettuce immunity, identifying both positive (LsBOS1) and negative (LsNAC53) regulators of defence against B. cinerea, as well as downstream target genes. These data provide a high level of detail on defence-induced transcriptional change in a crop species and a GRN with the ability to predict transcription factors mediating disease resistance both in lettuce and other species.

plant biology↗

bioRxiv2021

Bacteriophage adaptation to a mammalian mucosa reveals a trans-domain evolutionary axis

The majority of viruses within the human gut are obligate bacterial viruses known as bacteriophages (phages)1. Their bacteriotropism underscores the study of phage ecology in the gut, where they sustain top-down control2-4 and co-evolve5 with gut bacterial communities. Traditionally, these were investigated empirically via in vitro experimental evolution6-8 and more recently, in vivo models were adopted to account for gut niche effects4,9. Here, we probed beyond conventional phage-bacteria co-evolution to investigate the potential evolutionary interactions between phages and the mammalian "host". To capture the role of the mammalian host, we recapitulated a life-like mammalian gut mucosa using in vitro lab-on-a-chip devices (to wit, the gut-on-a-chip) and showed that the mucosal environment supports stable phage-bacteria co-existence. Next, we experimentally evolved phage populations within the gut-on-a-chip devices and discovered that phages adapt by de novo mutations and genetic recombination. We found that a single mutation in the phage capsid protein Hoc - known to facilitate phage adherence to mucus10 - caused altered phage binding to fucosylated mucin glycans. We demonstrated that the altered glycan-binding phenotype provided the evolved mutant phage a competitive fitness advantage over their ancestral wildtype phage in the gut-on-a-chip mucosal environment. Collectively, our findings revealed that phages - in addition to their evolutionary relationship with bacteria - are also able to engage in evolution with the mammalian host.

microbiology↗