Biology subjects

Daniels, E.

Publications and source records attributed to Daniels, E..

4 recordsLinked to original sources

bioRxiv2026

Integrated luminescence and phenotypic profiling for drug discovery in a zebrafish model of Marfan syndrome

BackgroundMarfan syndrome (MFS) is a life-threatening heritable connective tissue disorder caused by pathogenic variants in fibrillin-1, characterized by progressive cardiovascular disease. Current medical therapies slow disease progression but do not prevent major complications, underscoring the need for new treatment strategies and unbiased discovery approaches. MethodsWe used a zebrafish model of MFS lacking fibrillin-3 (fbn3-/-), which recapitulates key cardiovascular phenotypes including cardiac stress, valvular defects, arrhythmia, and aortic dilation. To enable sensitive, quantitative assessment of cardiac stress, we generated a novel transgenic zebrafish reporter expressing secreted nanoluciferase under control of the stress-responsive nppb promoter. This reporter was combined with morphological phenotyping and bulbus arteriosus (BA) imaging. We evaluated standard MFS therapies, targeted modulators of TGF-{beta} signaling, and performed an unbiased high-throughput drug screen of over 1 500 clinically approved compounds across multiple developmental treatment windows. Resultsfbn3-/- larvae exhibited markedly elevated nppb activity that correlated with phenotypic severity and peaked during stages of highest mortality. The nanoluciferase reporter provided a [~]1 000-fold dynamic range, substantially outperforming Firefly luciferase-based assays. Pharmacological inhibition of TGF-{beta} signaling produced transient or deleterious effects, while {beta}-blockers, losartan, and allopurinol failed to consistently improve cardiac stress, pericardial edema, or BA dilation. The unbiased high-throughput drug screen identified a small number of primary and secondary hits; however, none demonstrated reproducible phenotypic rescue upon rigorous multi-dose, multi-time window validation. ConclusionsThis study establishes a sensitive zebrafish-based platform for early, quantitative assessment of cardiovascular stress in MFS. Our findings highlight the limited efficacy of current therapies, the context-dependent nature of TGF-{beta} modulation, and the biological complexity underlying MFS pathogenesis. Although no definitive therapeutic candidates were identified, this work lays a robust foundation for expanded unbiased discovery efforts aimed at identifying disease-modifying interventions for MFS.

pharmacology and toxicology↗

bioRxiv2023

Fast and efficient root phenotyping via pose estimation

Image segmentation is commonly used to estimate the location and shape of plants and their external structures. Segmentation masks are then used to localize landmarks of interest and compute other geometric features that correspond to the plants phenotype. Despite its prevalence, segmentation-based approaches are laborious (requiring extensive annotation to train), and error-prone (derived geometric features are sensitive to instance mask integrity). Here we present a segmentation-free approach which leverages deep learning-based landmark detection and grouping, also known as pose estimation. We use a tool originally developed for animal motion capture called SLEAP (Social LEAP Estimates Animal Poses) to automate the detection of distinct morphological landmarks on plant roots. Using a gel cylinder imaging system across multiple species, we show that our approach can reliably and efficiently recover root system topology at high accuracy, few annotated samples, and faster speed than segmentation-based approaches. In order to make use of this landmark-based representation for root phenotyping, we developed a Python library (sleap-roots) for trait extraction directly comparable to existing segmentation-based analysis software. We show that landmark-derived root traits are highly accurate and can be used for common downstream tasks including genotype classification and unsupervised trait mapping. Altogether, this work establishes the validity and advantages of pose estimation-based plant phenotyping. To facilitate adoption of this easy-to-use tool and to encourage further development, we make sleap-roots, all training data, models, and trait extraction code available at: https://github.com/talmolab/sleap-roots and https://osf.io/k7j9g/.

plant biology↗

bioRxiv2019

Progress toward the identification and stacking of crucial domestication traits in pennycress

The oilseed species Thlaspi arvense (pennycress) is being domesticated as a new crop that can provide both important ecosystem services and intensify farmland output. Through the use of high throughput sequencing and phenotyping, along with classical mutagenesis key traits needed for pennycress domestication have been identified. Domestication traits identified herein include reduced pod shatter, early maturity, reduced seed glucosinolate levels, and improved oil fatty acid content. By taking advantage of pennycress close genetic relationship with Arabidopsis thaliana, the causative mutations responsible for each of these traits have been identified. These mutations have been used to develop molecular markers to begin to stack the traits into individual lines.

plant biology↗

bioRxiv2017

Spring flowering habit in field pennycress (Thlaspi arvense) has arisen multiple independent times

- Pennycress (Thlaspi arvense L.) is currently being developed as a new cold-season oilseed crop. Like many Brassicaceae, pennycress can exhibit either a winter or spring annual phenotype. In Arabidopsis, mutations in negative regulators of flowering, including FLOWERING LOCUS C (FLC) and FRIGIDA can cause the transition to a spring annual habit. The genetics underlying the difference between spring and winter annual pennycress are currently unknown.\n\n- Using whole genome sequencing across wild spring annual pennycress accessions, co-segregation analyses, and comparative genomics approaches, we identify new alleles of TaFLC and explore their geographic distribution.\n\n- We report that loss of function mutations in TaFLC confer the spring annual phenotype in pennycress. We have also identified four natural alleles of TaFLC that confer a spring annual growth habit. The two spring annual FLC alleles present in European accessions were only identified in accessions collected in Montana, USA.\n\n- In pennycress, the spring annual habit has arisen several independent times. Accessions harboring the two European alleles were introduced to North America, likely after the species became a widespread on the continent. These findings provide new information on the natural history of the introduction and spread of the spring annual phenotype in pennycress.

plant biology↗