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Taylor, R.

Publications and source records attributed to Taylor, R..

At least 19 recordsLinked to original sources

Eyes on the prize: Mice deploy task-driven saccades during naturalistic foraging

Active sensing allows organisms to shape incoming sensory information through self-generated actions, and saccadic eye movements provide a key readout of this process in vision. In primates, saccades are strongly modulated by cognitive variables such as uncertainty, value, and behavioural goals, particularly in complex, naturalistic settings. In rodents, by contrast, saccades have largely been interpreted as reflexive or compensatory, and evidence that they are modulated by cognitive state, such as trial outcome, expectation, or task demands, has remained sparse. Here, we examined how mice use saccades during a vision-dependent foraging task in a traversable immersive virtual environment with naturalistic stimuli. We correlated their saccade dynamics with behavioural strategies observed within the virtual environment. Target-directed saccades emerged specifically when informative sensory evidence was available, but also occurred anticipatorily when animals could rely on previously learned spatial contingencies, indicating that saccades were guided not only by immediate visual input but also by internal representations. Strikingly, the temporal structure of inter-saccade intervals resembled signatures previously reported in primates and lengthened with increased processing demand following changes in task contingencies. Together, these findings show that mouse saccades are not merely reflexive gaze corrections, but form part of a cognitively modulated active sampling strategy. More broadly, they suggest that key principles of active visual sensing may be conserved across species and establish mouse oculomotor behaviour as a tractable readout of internal cognitive state.

neuroscience↗

Radioligand therapy in combination with CAR T cells overcomes the heterogeneous immunosuppressive prostate tumor microenvironment

177Lu-PSMA-617 (PluvictoTM, Lu-177 RLT) is an FDA-approved targeted radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC), but its durability of response to this singular approach poses a challenge to the field. Chimeric antigen receptor (CAR) T cell therapy has revolutionized clinical practice for hematological malignancies, but its clinical development for solid tumors, including mCRPC, has been encumbered by antigen heterogeneity and the immunosuppressive tumor microenvironment (TME). Here, we evaluate the therapeutic combination of Lu-177 RLT and PSCA-CAR T cells to overcome these barriers. In human xenograft and mouse syngeneic prostate cancer models with homogeneous or heterogeneous antigen expression, the sequential administration of Lu-177 RLT, cyclophosphamide (Cy), and PSCA-CAR T cells improves tumor control and prolongs survival compared to monotherapies. Mechanistically, Lu-177 RLT alone or with Cy remodels the TME by promoting pro-inflammatory myeloid responses and activating endogenous T cells, while enhancing CAR T cell activation and effector function. We additionally evaluated 225Ac-PSMA-617 RLT as an emerging approach in combination with CAR T cells and observed anti-tumor responses, supporting its potential as an alternative RLT partner. These findings support RLT as an immune priming strategy to enhance CAR T cell therapy and provide a rationale for clinical translation of this combination in mCRPC. One Sentence SummaryCombining 177Lu-PSMA-617 radioligand therapy with PSCA-CAR T cells improves tumor control and survival in prostate cancer models by overcoming the antigen heterogeneity and reshaping the immunosuppressive tumor microenvironment.

cancer biology↗

Ryanodine receptor 1 ( RYR1 ) patient-derived muscle cells recapitulate disease phenotypes in 2D and 3D culture models

The Ryanodine Receptor 1 (RyR1) is the major Ca2+ release channel in skeletal muscle and plays a crucial role in excitation-contraction coupling. Pathogenic variants in RYR1 are the most common cause of congenital myopathy, for which there are no approved treatments. Patient-centric disease models may help to facilitate the design and screening of novel therapeutics in a human genomic context. In this report, we describe the differentiation of five dominant RYR1-related myopathy patient-derived induced pluripotent stem cell (iPSC) lines into muscle progenitor cells (MPCs), and subsequently into multinucleated myotubes in 2- and 3- Dimensional (D) culture models. In 2D, we show significantly reduced Ca2+ release in a patient line compared to a healthy control following stimulation with caffeine. In 3D engineered muscle tissues (EMTs), patient-relevant phenotypes including reduced twitch amplitude, delayed relaxation and altered force-frequency relationships were observed in a patient line compared to two healthy controls. We also show that the 2D cultures are a suitable platform for screening the efficacy and cellular toxicity of antisense oligonucleotide therapeutics. Together, these results suggest that iPSC-derived skeletal muscle cultures are useful models for understanding the pathobiology of RYR1-related myopathies and as a testbed for emerging treatments.

Cell Biology↗

Mapping memory-guided saccade population receptive fields reveals principles of cortical organization along the human intraparietal sulcus

The intraparietal sulcus is a central hub for motor planning and sensorimotor integration. Its responses are known to support coordinate transformations across reference frames and modalities--for example, eye-position gain fields that convert retinotopic, fovea-centred signals into head-centred representations. In the oculomotor domain, the human intraparietal sulcus is sensitive to eye-movement planning and has been extensively studied using memory-guided saccade paradigms. These classic approaches have revealed topographic organization and contralateral sensitivity for preferred direction in saccade planning and execution. However, such designs provide detailed information about preferred direction; they do not probe tuning width: how narrowly or broadly a given cortical location responds around its preferred direction. At present, it remains unclear whether and how tuning width is organized along the human intraparietal sulcus. Critically, neurophysiological studies in non-human primates do not offer systematic and extensive measurements of tuning width. Moreover, the relationship between tuning width and preferred direction at the population level in human intraparietal cortex is unknown. Here, we address these questions using a forward-modelling approach combined with high-field (7-Tesla) functional MRI. We observe contralateral preference for preferred direction in saccade planning and execution, as well as a novel large-scale organization of preferred saccade tuning width, in vivo, in humans. Highlightssaccade planning and execution tuning width is arranged topographically along human early visual cortex and human intraparietal sulcus; specificity of voxel-level saccade planning and execution decreases along the visual hierarchy; specificity of population-level saccade planning and execution increases along the visual hierarchy; forward modelling applied to memory-guided saccade paradigm outperforms the standard phase-encoding approach;

neuroscience↗

Specific deletion of interleukin-1 beta in microglia improves acute outcome and modulates neurogenesis after ischemic stroke

Interleukin-1 (IL-1) signaling is a major driver of post-ischemic neuroinflammation, yet the cell- and isoform-specific roles of the two major IL-1 receptor type 1 agonists, IL-1 and IL-1{beta}, remain incompletely defined in the context of stroke. Microglia rapidly express IL-1 after cerebral ischemia, whereas IL-1{beta} expression is delayed and restricted to a small subset of microglia and infiltrating immune cells. Here, we investigated for the first time the specific contribution of microglial-derived IL-1{beta} to acute injury and post-stroke neurorepair after transient middle cerebral artery occlusion in male and female mice, through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Deletion of microglial IL-1{beta} improved acute neurological outcome, reduced neutrophil accumulation in the ischemic brain and dampened systemic inflammatory cytokines. These effects were most evident during the acute phase and in female in mice. In contrast, long-term functional recovery was largely unaffected. However, microglial IL-1{beta} deletion differentially regulated post-stroke neurogenesis, enhancing subventricular zone neurogenic responses and ectopic neuroblast migration while limiting hippocampal neurogenesis. Together, these findings identify microglial IL-1{beta} as a key amplifier of early inflammatory injury after stroke, exerting region-specific effects on neurogenic niches, and highlight distinct, non-redundant roles for microglial IL-1 isoforms in ischemic brain injury and repair.

neuroscience↗

Pharmacological activation of AMPK rescues mitophagy defects in models of FBXL4-related mitochondrial DNA depletion syndrome

Distinct mitophagy pathways can eliminate not only damaged mitochondria but also healthy ones. In Mitochondrial DNA Depletion Syndrome 13 (MTDPS13), dysregulated BNIP3/NIX-driven mitophagy of functional mitochondria is thought to be the key pathological driver. Patient mutations in the E3 ubiquitin ligase FBXL4 impair the proteasomal degradation of the mitophagy receptors BNIP3 and NIX, causing their accumulation and excessive mitophagy. As a result, mitochondrial content and oxidative phosphorylation decline sharply across multiple tissues, leading to early mortality, with no effective treatments currently existing. In this study, we demonstrate that activating AMPK markedly suppresses BNIP3/NIX-dependent mitophagy and restores mitochondrial respiration in FBXL4-deficient cells. Using both fibroblasts derived from MTDPS13 patients and a chemically-induced in vivo model, we show that small molecule AMPK activation inhibits BNIP3/NIX-mediated mitophagy and recovers mitochondrial content. This work therefore highlights the therapeutic potential of targeting AMPK in MTDPS13.

cell biology↗

Directing fratricide within T cell products using an anti-uPAR chimeric antigen receptor to drive the production of potent therapeutic cells

Cell therapy manufacturing of primary T cells often results in heterogeneous cell populations within a final product, with many cells lacking desired of receptor expression or those that have exhausted or other dysfunctional phenotypes. Here, we design a novel cell-intrinsic strategy to genetically reprogram primary human T cells to autonomously detect and eliminate dysfunctional cells. This integrated detection and elimination process, known as directed fratricide, is programmed via nonviral CRISPR genome-editing to eliminate the T cell receptor (TCR) alpha chain (TRAC gene knockout) and integrate a chimeric antigen receptor (CAR) against the urokinase-type plasminogen activator receptor (uPAR), also known as CD87. Within these cell products, strong T cell stimulation or activation during manufacturing causes a small subset of cells to express uPAR, which subsequently triggers CAR-mediated killing by a separate subset of cells within the product. This fratricide induces proliferation in the desired cells and destroys undesired cells, a process that could be modeled computationally and controlled robustly via supplements to the culture media. The strategy enabled enrichment of anti-uPAR and anti-GD2 CAR T cell products up to [≥]99% CAR+/TCR-, favoring a stem cell memory-like phenotype (CD45RAhigh/CD62Lhigh). Understanding growth dynamics among T cell subsets and reprogramming them via CRISPR could accelerate the biomanufacturing of potent cell products without extensive selection methods. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/684419v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@199d85forg.highwire.dtl.DTLVardef@14c638aorg.highwire.dtl.DTLVardef@1b3322org.highwire.dtl.DTLVardef@1ba253d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Enhancing CRISPR Education: A Plug-And-Play Framework for Teaching Gene Editing in Plant Biology

Modern molecular biology tools and technologies such as CRISPR have sped up scientific discovery. From an educational perspective, these advancements are both exciting and overwhelming. Educators shaping these future scientists face the ongoing challenge of staying compliant with the latest developments in molecular biology while finding effective ways to teach these discoveries. As the use of CRISPR gene editing technology continues to expand globally, there is an increasing need for a workforce that is both knowledgeable about its theoretical foundations and trained in its practical use. While advanced, technology-driven STEM courses have the potential to improve student retention, they are often lecture-heavy and lack intentional engagement strategies that support deeper learning. Moreover, agriculture is the second most impacted sector by this technology, yet there is a significant lack of teaching materials focused on CRISPR in plant biology. To address these gaps, we developed a framework for teaching gene editing that incorporates multiple engagement strategies beyond traditional lecture-based instruction. This framework was implemented over two semesters in an Introduction to Gene Editing course at Tennessee State University, offered to both undergraduate and graduate students enrolled in a degree in Agricultural Sciences. This manuscript outlines the various strategies used in the course including active learning, multimodal instructional approaches and experiential learning strategies that can be adopted in other classrooms to effectively teach gene editing. Survey-based results from the course indicate a measurable increase in student comfort with designing and executing CRISPR-Cas based experiments. Societal Impact StatementPlant biology lacks accessible teaching materials for CRISPR, a powerful gene-editing technology widely used to improve agriculture. We developed an engaging framework to teach CRISPR concepts to advanced undergraduates and graduate students in plant sciences, which can be readily adopted by other instructors. The approach increased self-reported confidence in students and comfort in explaining CRISPR. Since instructors often have limited time to design interactive lessons, this framework offers a ready-to-use, effective strategy that makes CRISPR more widely available in classrooms, ultimately strengthening CRISPR literacy in the future agricultural workforce.

scientific communication and education↗

Bottom-up investigation of spatiotemporal glycocalyx dynamics with interferometric scattering microscopy

Over recent decades, the glycocalyx, an extracellular organelle comprised of a multitude of glycolipids, glycoproteins, proteoglycans and glycoRNA, has gained considerable interest in cellular biology. While research in this field has revealed its tremendous importance in evermore aspects of physiological and pathological cellular processes, many of the principles that govern the role of the glycocalyx in these processes on a molecular level are still unknown. In order to unravel the fundamental laws underlying glycocalyx function, new technologies are required that enable the distinction between individual subprocesses within the intricate environment of the glycocalyx. Here, we establish an experimental platform to investigate the dynamics of the glycocalyx at the nanometer and microsecond length and time scales in a bottom-up fashion. We synthesized defined model glycans and installed them on supported lipid bilayers, assembling glycocalyx model systems with tunable properties. By investigating these tunable model systems with interferometric scattering (iSCAT) microscopy, we gain access to the required spatiotemporal resolution. We found a strong correlation between the molecular structure of several investigated model glycans and global dynamics of the system. Our findings are corroborated by atomistic and coarsegrained molecular dynamics simulations. Our results provide the first direct experimental evidence on the relationship between glycan structure, organization, and dynamics, offering a robust and versatile basis for a quantitative understanding of glycocalyx biology and physics at the molecular level.

biophysics↗

The novel RNA polymerase I transcription inhibitor PMR-116 exploits a critical therapeutic vulnerability in a broad-spectrum of high MYC malignancies.

Ribosome biogenesis (RiBi) is a key determinant of cell growth and proliferation and is highly elevated in cancer due to the activation by oncogenes such as MYC. First-generation RiBi inhibitor CX-5461, while demonstrating clinical potential for cancer treatment, also induces DNA damage through off-target inhibition of TOP2 and potentially other mechanisms, bringing into question RiBi as a target for cancer therapy. In this study, we test second-generation RiBi inhibitor, PMR-116. PMR-116 exhibits improved drug-like properties compared to first-generation RiBi inhibitors and has robust anti-tumour activity in the absence of global DNA damage signalling in a broad range of pre-clinical models of haematologic and solid cancers, particularly in malignancies where MYC is either the driver of disease or is elevated. Thus, our work demonstrates that RiBi is a genuine target for cancer therapy and highlights the potential to exploit a critical therapeutic vulnerability in high-MYC human cancers with dismal therapeutic outcomes. Statement of significanceDespite the development of new cancer therapies, most advanced malignancies remain incurable. We demonstrate that PMR-116, a second-generation RiBi inhibitor, has robust therapeutic efficacy in preclinical models of cancer, offering great promise to treat a broad spectrum of human solid and haematologic malignancies, especially where MYC is a driver.

cancer biology↗

Sharing the Spotlight: Uncovering common attentional dynamics across species

Sustained attention is a key underlying process to many natural behaviours that are shared by multiple species. Yet the way it is commonly studied in a lab context precludes any meaningful cross-species comparisons. Here, we engaged mice, monkeys, and humans in the exact same, natural perceptual decision task in a VR environment. We captured their behaviour into several parameters along the speed/accuracy axes along which sustained attention is classically defined, and used HMMs to infer four attentional states. We show that the dynamics of these states, both in terms of their durations as well as the transitions between them, are much more similar between the species than might have been expected. Moreover, attentional state fluctuations seem to be internally generated. The task and analyses developed here represent a new approach to compare sustained attention across species in an objective, data-driven way.

animal behavior and cognition↗

The DREAM implant: A Lightweight, Modular and Cost-Effective Implant System for Chronic Electrophysiology in Head-fixed and Freely Behaving Mice

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. However, current methods for chronically implanting probes present steep trade-offs between cost, ease of use, size, adaptability and long-term stability. SUMMARYIntroducing a lightweight, cost-effective probe implant system for chronic electrophysiology in rodents, optimized for ease of use, probe recovery, experimental versatility and compatibility with behavior. This protocol introduces a novel chronic probe implant system for mice called the DREAM (Dynamic, Recoverable, Economical, Adaptable and Modular), designed to overcome the trade-offs associated with currently available options. The system provides a lightweight, modular and cost-effective solution with standardized hardware elements that can be combined and implanted in straightforward steps and explanted safely for recovery and multiple re-use of probes, significantly reducing experimental costs. The DREAM implant system integrates three hardware modules: (1) a microdrive that can carry all standard silicon probes, allowing experimenters to adjust recording depth across a travel distance of up to 7mm; (2) a 3D-printable, open-source design for a wearable Faraday cage covered in copper mesh for electrical shielding, impact protection and connector placement, and (3) a miniaturized head-fixation system for improved animal welfare and ease of use. The corresponding surgery protocol was optimized for speed (total duration: 2 hours), probe safety and animal welfare. The resulting implants had minimal impact on animals behavioral repertoire, were easily applicable in freely moving and head-fixed contexts and delivered clearly identifiable spike waveforms and healthy neuronal responses for weeks of data collection post-implant. Infections and other surgery complications were extremely rare. As such, the DREAM implant system is a versatile, cost-effective solution for chronic electrophysiology in mice, enhancing animal well-being, and enabling more ethologically sound experiments. Its design simplifies experimental procedures across various research needs, increasing accessibility of chronic electrophysiology in rodents to a wide range of research labs.

neuroscience↗

Thoughtful faces: inferring internal states across species using facial features

Animal behaviour is shaped to a large degree by internal cognitive states, but it is unknown whether these states are similar across species. To address this question, here we develop a virtual reality setup in which male mice and macaques engage in the same naturalistic visual foraging task. We exploit the richness of a wide range of facial features extracted from video recordings during the task, to train a Markov-Switching Linear Regression (MSLR). By doing so, we identify, on a singletrial basis, a set of internal states that reliably predicts when the animals are going to react to the presented stimuli. Even though the model is trained purely on reaction times, it can also predict task outcome, supporting the behavioural relevance of the inferred states. The relationship of the identified states to task performance is comparable between mice and monkeys. Furthermore, each state corresponds to a characteristic pattern of facial features that partially overlaps between species, highlighting the importance of facial expressions as manifestations of internal cognitive states across species.

animal behavior and cognition↗

Modelling the impact of rainfall events on increasing Vibrio vulnificus concentrations in Pacific oysters (Crassostrea gigas)

Vibrio vulnificus occurs naturally in seawater and causes debilitating, often fatal illnesses, particularly in people with underlying health issues such as liver disease. The illness can occur when raw molluscan shellfish that have bio-accumulated the organism are consumed. New Zealand seafood is not known to have caused any illnesses, although there have been wound infections. This study sought to better understand the effect of environmental conditions on concentrations of V. vulnificus in Pacific oysters in three harbours over the summer months of 2016-19. Fortnightly sampling at two harbours only once gave a most probable number (MPN) of >10 per g of oyster meat, while the third harbour regularly produced much higher counts (up to 220,000 per g). From 2017-19, weekly samples from three sites in this harbour (four in 2018) were tested. Eleven peaks in concentration were observed, all when seawater temperatures exceeded 20{degrees}C and after heavy rainfall had reduced the seawater salinity, usually to <25{per thousand} from the average of 32{per thousand}. A fitted structural equation model with temperature and salinity terms accounted for 60% of the variance in concentrations and rates of decline after concentration peaks averaged 1.05 log10 MPN per week. The rate of decline was highly variable so microbiological testing would be required to confirm this rate for use in food safety management. However, the results of the study will enable better risk management. ImportanceVibrio vulnificus is a deadly bacterium that naturally occurs in some seawater and can be concentrated in shellfish such as oysters. Consumers with underlying health issues who eat contaminated shellfish may suffer serious illnesses. New Zealand shellfish have never been known to cause such illnesses although the species is present in our seawater. The strains present may not be able to cause foodborne illness. We found that V. vulnificus could be present in high concentrations in farmed Pacific oysters in one of three studied harbours. This happened when seawater temperatures were warm and heavy rainfall reduced salinity. We developed a model based on seawater temperature and salinity that would be able to predict concentrations in shellfish, at least in this harbour. This will help industry and regulators manage the food safety risk should this organism become a public health issue. TweetWe modelled concentrations of Vibrio vulnificus in Pacific oysters after flood events and showed that seawater salinity and temperatures in previous 168 h affected them.

microbiology↗

Oligosaccharide production and signaling correlate with delayed flowering in an Arabidopsis genotype grown and selected in high

Since industrialization began, atmospheric CO2 ([CO2]) has increased from 270 to 415 ppm and is projected to reach 800-1000 ppm this century. Some Arabidopsis ecotypes delayed flowering in elevated [CO2] relative to current [CO2], while others showed no change or accelerations. To predict genotype-specific flowering behaviors, we must understand the mechanisms driving flowering response to rising [CO2]. [CO2] changes alter photosynthesis and carbohydrates in C3 plants. Plants sense carbohydrate levels and exogenous carbohydrate application influences flowering time and flowering transcript levels. We asked how organismal changes in carbohydrates and transcription correlate with changes in flowering time under elevated [CO2]. We used a genotype (SG) of Arabidopsis that was selected for high fitness at elevated [CO2] (700 ppm). SG delays flowering under elevated [CO2] (700 ppm) relative to current [CO2] (400 ppm). We compared SG to a closely related control genotype (CG) that shows no [CO2]- induced flowering change. We compared metabolomic and transcriptomic profiles in these genotypes at current and elevated [CO2] to assess correlations with flowering in these conditions. While both genotypes altered carbohydrates in response to elevated [CO2], SG had higher levels of sucrose than CG and showed a stronger increase in glucose and fructose in elevated [CO2]. Both genotypes demonstrated transcriptional changes, with CG increasing genes related to fructose 1,6-bisphosphate breakdown, amino acid synthesis, and secondary metabolites; and SG decreasing genes related to starch and sugar metabolism, but increasing genes involved in oligosaccharide production and sugar modifications. Genes associated with flowering regulation within the photoperiod, vernalization, and meristem identity pathways were altered in these genotypes. Elevated [CO2] may act through carbohydrate changes to influence transcription in both genotypes and delayed flowering in SG. Changes in the oligosaccharide pool may contribute to delayed flowering in SG. This work extends the literature exploring genotypic-specific flowering responses to elevated [CO2].

plant biology↗

Membrane and glycocalyx tethering of DNA nanostructures for enhanced uptake

DNA nanostructures (DNs) have been increasingly utilized in biosensing, drug delivery, diagnostics and therapeutics, because of their programmable assembly, control over size and shape, and ease of functionalization. However, the low cellular uptake of DNs has limited their effectiveness in these biomedical applications. Here we demonstrate the potential of membrane and glycocalyx binding as general strategies to enhance the cellular uptake of DNs. By targeting the plasma membrane and cell-surface glycocalyx, the uptake of all three distinct DNs is significantly enhanced as compared to uptake of bare DNs. We also demonstrate the viability of single-step membrane labeling by cholesterol-DNs as competitive with previous multistep approaches. Further, we show that the endocytic pathway of membrane-bound DNs is an interdependent process that involves scavenger receptors, clathrin-, and caveolinmediated endocytosis. Our findings may potentially expand the toolbox for effective cellular delivery of DNA nanostructured systems.

bioengineering↗

Biventricular interaction during acute left ventricular ischemia in mice: a combined in-vivo and in-silico approach

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n=3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.

bioengineering↗

From Multi-Allele Fish to Non-Standard Environments, How ZFIN Assigns Phenotypes, Human Disease Models, and Gene Expression Annotations to Genes

Danio rerio is a model organism used to investigate vertebrate development. Manipulation of the zebrafish genome and resultant gene products by mutation or targeted knockdown has made the zebrafish a good system for investigating gene function, providing a resource to investigate genetic contributors to phenotype and human disease. Phenotypic outcomes can be the result of gene mutation, targeted knockdown of gene products, manipulation of experimental conditions, or any combination thereof. Zebrafish have been used in various genetic and chemical screens to identify genetic and environmental contributors to phenotype and disease outcomes. The Zebrafish Information Network (ZFIN) is the central repository for genetic, genomic, and phenotypic data that result from research using Danio rerio. Here we describe how ZFIN annotates phenotype, expression, and disease model data across various experimental designs, how we computationally determine wild-type gene expression, the phenotypic gene, and how these results allow us to propagate gene expression, phenotype, and disease model data to the correct gene, or gene related entity.

bioinformatics↗