Biology subjects

Navoly, G.

Publications and source records attributed to Navoly, G..

4 recordsLinked to original sources

bioRxiv2026

Transcriptome-wide association study and fly experiments uncover the role of CoA synthase in ageing across species.

While significant progress has been made in understanding the genetic architecture of ageing in model organisms, our understanding of human ageing remains limited. We performed a multi-tissue Transcriptome-wide association study (TWAS) on human lifespan, integrating GWAS data from >1 million parental lifespans with gene expression prediction models derived from reference transcriptomic datasets; followed by replication using healthspan and longevity phenotypes as additional readouts of ageing. The TWAS uncovered 563 significant gene associations, of which 139 replicated. TOMM40, encoding a component of the mitochondrial outer membrane translocase that is fundamental for mitochondrial function, had the strongest association with parental lifespan and longevity and was fine-mapped as a putatively causal lifespan gene at the APOE-TOMM40 region. Uniquely in our study, we identified fly orthologues of replicating genes and examined if modulating their expression impacts Drosophila longevity. The nine novel associations with all three ageing outcomes included COASY, encoding Coenzyme A synthase. Knocking down its fly orthologue, Ppat-dpck, resulted in significant lifespan extension in flies. Hence, in addition to discovering new genes associated with human ageing, by combining human TWAS with experimental Drosophila work, we provide evidence for the role of COASY (Ppat-dpck) in ageing across species. Significance statementExtensive research on ageing has been conducted in Drosophila and C.elegans due to their short lifespan and experimental tractability. However, in human genetic research, only a few loci have been consistently replicated. To bridge this gap, we conducted a transcriptome-wide association study (TWAS) followed by experimental validation in Drosophila. TWAS revealed 139 significant and replicating gene associations, including COASY. Knockdown of its fly orthologue (Ppat-dpck) significantly extended fly lifespan, validating its roles in ageing across species. Thus, integrating multiple ageing outcomes through TWAS in human genetic research can uncover robust associations and highlight genes involved in fundamental ageing mechanisms.

genetics↗

bioRxiv2023

Understanding Campylobacter coli isolates from the Vietnamese meat production network; a pilot study

Changing farming practices and the associated increase in the use of antibiotics are amongst the main drivers shaping the global increase of Campylobacter infections. The effects farming practices have on Campylobacter species, need to be studied at the global scale, particularly in emerging middle-income countries, where the demand for low-cost poultry meat is rising. While C. jejuni causes the majority of poultry associated diarrhoea, C. coli causes a significant amount of disease but are relatively understudied. In this study we characterised seven C. coli strains isolated from poultry farms and markets in Hanoi, Vietnam. Comprehensive data sets of bacterial Whole-Genome Sequencing; and phenotypic assays, such as, growth, motility, antimicrobial resistant testing along with virulence testing were performed to reveal the genetic relatedness and pathophysiological characteristics of seven C. coli strains. Six isolates were classified as multi-drug resistant, with all isolates resistant to ciprofloxacin, nalidixic acid and tetracycline, but susceptible to phenicols. All isolates had similar growth rates, while five were hyper-motile. Lethality of the isolates towards a tractable host-model system, larvae of the greater wax moth Galleria mellonella, often used to determine Campylobacter virulence was demonstrated for the first time for C. coli. Multilocus sequence typing data correlates with North American, European, and Asian isolates from patients suffering from gastroenteritis, emphasising the global spread of these strains. This work demonstrates that C. coli, with high levels of antimicrobial resistance, is an understudied global threat. Data summaryGenBank database with accession numbers JAKGTW000000000, JAKGTV000000000, JAKGTS000000000, JAKGTU000000000, JAKGTT000000000, JAKGTR000000000 and CP091310 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTW000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTV000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTS000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTU000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTT000000000 https://www.ncbi.nlm.nih.gov/nuccore/JAKGTR000000000 https://www.ncbi.nlm.nih.gov/nuccore/CP091310.1 The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2022

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗

bioRxiv2020

Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures.

Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remains unclear. Here, using a modified ex vivo organotypic culture system we show that donor ENSC-derived cells integrate across the colonic wall in a dynamic fashion, across a three-week period. We further show that donor cells display two integrative patterns; longitudinal migration and medial invasion which allow donor cells to populate colonic tissue. Moreover, we demonstrate that significant remodelling of the intestinal ECM, and musculature, occurs upon transplantation to facilitate donor cell integration. Thus, our results provide critical evidence on the timescale, and mechanisms, which regulate donor ENSC integration within recipient gut tissue.

cell biology↗