Biology subjects

Bird, C. E.

Publications and source records attributed to Bird, C. E..

3 recordsLinked to original sources

bioRxiv2025

Anthropocene genetic diversity loss in the marine tropics

Genetic diversity is a crucial component of biodiversity, and as such, its maintenance and preservation is of high conservation concern. Tropical environments are undergoing intense rates of environmental change, and these changes may be driving large declines in genetic diversity. However, data on genetic diversity are highly skewed towards temperate regions. The degree to which diversity loss has occurred in tropical species, particularly marine species, remains an open and important question. Here, we directly compare genomic data from modern and museum collections of two commercially-harvested nearshore marine fishes (Equulites laterofenestra and Gazza minuta) gathered from a single location in the Philippines, spanning a century of intense environmental change. These data reveal a marked loss in genetic diversity and evidence for multiple orders of magnitude reductions in effective population size (Ne) in both species, indicating substantial genomic erosion. Such a decline highlights the long-lasting genomic consequences of anthropogenic activity and sheds light on an, until-now, invisible loss of diversity from the most biodiverse ocean region. Significance StatementRecent reports have shown that genetic diversity in marine fishes has declined either slightly or not at all during the Anthropocene. However, almost all studies investigating marine genetic diversity loss have been from temperate latitudes, whereas tropical marine environments experience some of the most intense human impacts. Here, we directly compare genomic data from modern and historical specimens of two commercially-harvested fishes from the Philippines. We show that marine species in the tropics have already lost substantial genetic diversity and may have undergone severe bottlenecks over the past century. These results shine a light on the previously invisible loss of genetic diversity in the most biodiverse region of the ocean, and they emphasize the evolutionary consequences of the Anthropocene.

ecology↗

bioRxiv2021

Semi-automated computational assessment of cancer organoid viability using rapid live-cell microscopy

The creation of patient-derived cancer organoids represents a key advance in preclinical modeling and has recently been applied to a variety of human solid tumor types. However, conventional methods used to assess cellular viability in tissue specimens are poorly suited for the evaluation of cancer organoids because they are time-intensive and involve tissue destruction. To address this issue, we established a suite of 3-dimensional patient-derived glioma organoids, treated them with chemoradiotherapy, stained organoids with non-toxic cell dyes, and imaged them using a rapid laser scanning confocal microscopy method termed "Apex Imaging". We then developed and tested a fragmentation algorithm to quantify heterogeneity in the topography of the organoids as a potential surrogate marker of viability. This algorithm, SSDquant, provides a 3-dimensional visual representation of the organoid surface and a numerical measurement of the sum-squared distance (SSD) from the derived mass center of the organoid. We tested whether SSD scores correlate with traditional immunohistochemistry-derived cell viability markers (cellularity and cleaved caspase 3 expression) and observed statistically significant associations between them using linear regression analysis. Our work describes a quantitative, non-invasive approach for the serial measurement of patient-derived cancer organoid viability, thus opening new avenues for the application of these models to studies of cancer biology and therapy.

bioinformatics↗

bioRxiv2021

De Novo Pyrimidine Synthesis is a Targetable Vulnerability in IDH Mutant Glioma

Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they appear less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1 mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH mutant gliomas. Mechanistically, this vulnerability selectively applies to de novo pyrimidine, but not purine, synthesis because glioma cells engage disparate programs to produce these nucleotide species and because IDH oncogenes increase DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation.

cancer biology↗