Model Organisms and Model Environments: A Rodent Laboratory in Science, Medicine and Society

In recent years there has been increasing interest in the role of animals in science and medicine. While historians have tended to focus on the processes of standardisation, increasing attention is being given to the surprising and unexpected elements of the model organism. Experimental organisms are, simultaneously, both artefacts and samples of nature. Rachel Ankeny and Sabina Leonelli put it clearly and succinctly: ‘they are systems that have been engineered and modified to enable the controlled investigation of specific phenomena, yet at the same time they remain largely mysterious products of millennia of evolution, whose behaviours, structures, and physiology are for the most part still relatively ill-understood by scientists.’ In continuously generating new questions, organisms provide novelty so essential to successful experimental systems. They are, as Hans-Jörg Rheinberger would argue, scientific objects or ‘epistemic things’, not merely predictable ‘technical objects’.

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“What You Need, Baby, I Got It”: Transposable Elements as Suppliers of Cis-Operating Sequences in Drosophila

Biology ◽

10.3390/biology9020025 ◽

2020 ◽

Vol 9 (2) ◽

pp. 25 ◽

Cited By ~ 1

Author(s):

Roberta Moschetti ◽

Antonio Palazzo ◽

Patrizio Lorusso ◽

Luigi Viggiano ◽

René Massimiliano Marsano

Keyword(s):

Transposable Elements ◽

Transcriptional Control ◽

Environmental Changes ◽

Model Organism ◽

Model Organisms ◽

Regulatory Sequences ◽

Transcriptional Pattern ◽

Constitutive Components ◽

Host Genes

Transposable elements (TEs) are constitutive components of both eukaryotic and prokaryotic genomes. The role of TEs in the evolution of genes and genomes has been widely assessed over the past years in a variety of model and non-model organisms. Drosophila is undoubtedly among the most powerful model organisms used for the purpose of studying the role of transposons and their effects on the stability and evolution of genes and genomes. Besides their most intuitive role as insertional mutagens, TEs can modify the transcriptional pattern of host genes by juxtaposing new cis-regulatory sequences. A key element of TE biology is that they carry transcriptional control elements that fine-tune the transcription of their own genes, but that can also perturb the transcriptional activity of neighboring host genes. From this perspective, the transposition-mediated modulation of gene expression is an important issue for the short-term adaptation of physiological functions to the environmental changes, and for long-term evolutionary changes. Here, we review the current literature concerning the regulatory and structural elements operating in cis provided by TEs in Drosophila. Furthermore, we highlight that, besides their influence on both TEs and host genes expression, they can affect the chromatin structure and epigenetic status as well as both the chromosome’s structure and stability. It emerges that Drosophila is a good model organism to study the effect of TE-linked regulatory sequences, and it could help future studies on TE–host interactions in any complex eukaryotic genome.

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Super models

Physiological Genomics ◽

10.1152/physiolgenomics.00075.2002 ◽

2003 ◽

Vol 13 (1) ◽

pp. 15-24 ◽

Cited By ~ 57

Author(s):

Maureen M. Barr

Keyword(s):

Model Organism ◽

Model System ◽

Biological Pathways ◽

Cellular Biology ◽

Model Organisms ◽

Biological Processes ◽

Nematode Caenorhabditis Elegans ◽

Yeast Saccharomyces Cerevisiae ◽

Experimental Systems ◽

Genomics And Proteomics

Model organisms have been used over a century to understand basic, conserved biological processes. The study of these experimental systems began with genetics and development, moved into molecular and cellular biology, and most recently propelled into functional genomics and proteomics. The goal of this review is simple: to discuss the place of model organisms in “The Age of the Ome”: the genome, the transcriptome, and the proteome. This review will address the following questions. What exactly is a model organism? What characteristics make an excellent model system? Using the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans as examples, this review will discuss these issues with the aim of demonstrating how model organisms remain indispensable scientific tools for understanding complex biological pathways and human disease.

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Are Model Organisms Theoretical Models?

Disputatio ◽

10.1515/disp-2017-0015 ◽

2017 ◽

Vol 9 (47) ◽

pp. 471-498

Author(s):

Veli-Pekka Parkkinen

Keyword(s):

Animal Models ◽

Causal Structure ◽

Model Organism ◽

Theoretical Models ◽

Theoretical Modelling ◽

Model Organisms ◽

Target System ◽

Inductive Step ◽

Epistemic Role

AbstractThis article compares the epistemic roles of theoretical models and model organisms in science, and specifically the role of non-human animal models in biomedicine. Much of the previous literature on this topic shares an assumption that animal models and theoretical models have a broadly similar epistemic role—that of indirect representation of a target through the study of a surrogate system. Recently, Levy and Currie (2015) have argued that model organism research and theoretical modelling differ in the justification of model-to-target inferences, such that a unified account based on the widely accepted idea of modelling as indirect representation does not similarly apply to both. I defend a similar conclusion, but argue that the distinction between animal models and theoretical models does not always track a difference in the justification of model-to-target inferences. Case studies of the use of animal models in biomedicine are presented to illustrate this. However, Levy and Currie’s point can be argued for in a different way. I argue for the following distinction. Model organisms (and other concrete models) function as surrogate sources of evidence, from which results are transferred to their targets by empirical extrapolation. By contrast, theoretical modelling does not involve such an inductive step. Rather, theoretical models are used for drawing conclusions from what is already known or assumed about the target system. Codifying assumptions about the causal structure of the target in external representational media (e.g. equations, graphs) allows one to apply explicit inferential rules to reach conclusions that could not be reached with unaided cognition alone (cf. Kuorikoski and Ylikoski 2015).

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Homeostasis in the Central Dogma of Molecular Biology: the importance of mRNA instability

10.1101/599050 ◽

2019 ◽

Author(s):

José E. Pérez-Ortín ◽

Vicente Tordera ◽

Sebastián Chávez

Keyword(s):

Molecular Biology ◽

Model Organism ◽

Model Organisms ◽

Published Data ◽

Central Dogma ◽

E Coli ◽

Response Capacity ◽

Cultured Human Cells ◽

The Cost

AbstractCell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organismS. cerevisiae. Here we extend this study by comparing published data from three other model organisms:E. coli, S. pombeand cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A constant ratio appears between the average decay and dilution rates during cell growth for mRNA, but not for proteins. We postulate that this is due to a trade-off between the cost of synthesis and the response capacity. This compromise takes place at the transcription level, but is not possible at the translation level as the high stability of proteins,versusthat of mRNAs, precludes it. We hypothesize that the middle-place role of mRNA in theCentral Dogmaof Molecular Biology and its chemical instability make it more suitable than proteins for the fast changes needed for gene regulation.Graphical Abstract

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Insights into LIS1 function in cargo-adapter-mediated dynein activation in vivo

10.1101/683995 ◽

2019 ◽

Author(s):

Rongde Qiu ◽

Jun Zhang ◽

Xin Xiang

Keyword(s):

Aspergillus Nidulans ◽

Mechanism Of Action ◽

Developmental Disorder ◽

Model Organism ◽

Cytoplasmic Dynein ◽

Significant Extent ◽

Experimental Systems ◽

Microtubule Motor

AbstractDeficiency of the LIS1 protein causes lissencephaly, a brain developmental disorder. Although LIS1 binds the microtubule motor cytoplasmic dynein and has been linked to dynein function in many experimental systems, its mechanism of action remains unclear. Here we revealed the function of LIS1 in cargo-adapter-mediated dynein activation in the model organism Aspergillus nidulans. Specifically, we found that overexpressed cargo adapter HookA (Hook in A. nidulans) missing its cargo-binding domain (ΔC-HookA) causes dynein and its regulator dynactin to relocate from the microtubule plus ends to the minus ends, and this dramatic relocation requires LIS1 and its binding protein NudE. Astonishingly, the requirement for LIS1 or NudE can be bypassed to a significant extent by specific mutations that open the auto-inhibited “phi-dynein” in which the motor domains of the dynein dimer are held close together. Our results suggest a novel mechanism of LIS1 action: it promotes the switch of dynein from the auto-inhibited state to an open state to facilitate dynein activation.SummaryThis study reveals the role of Lissencephaly 1 (LIS1) in cargo-adapter-mediated dynein activation. Furthermore, it discovers a novel mechanism of LIS1 action involving a switch of dynein from an auto-inhibited state to an active state.

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The past, present and future of Dictyostelium as a model system

The International Journal of Developmental Biology ◽

10.1387/ijdb.190128sb ◽

2019 ◽

Vol 63 (8-9-10) ◽

pp. 321-331 ◽

Cited By ~ 2

Author(s):

Salvatore Bozzaro

Keyword(s):

Dictyostelium Discoideum ◽

Social Evolution ◽

Model Organism ◽

Model Organisms ◽

Human Genes ◽

The Social ◽

Microbial Infections ◽

Technological Developments ◽

Soil Amoeba

The social amoeba Dictyostelium discoideum has been a preferred model organism during the last 50 years, particularly for the study of cell motility and chemotaxis, phagocytosis and macropinocytosis, intercellular adhesion, pattern formation, caspase-independent cell death and more recently autophagy and social evolution. Being a soil amoeba and professional phagocyte, thus exposed to a variety of potential pathogens, D. discoideum has also proven to be a powerful genetic and cellular model for investigating host-pathogen interactions and microbial infections. The finding that the Dictyostelium genome harbours several homologs of human genes responsible for a variety of diseases has stimulated their analysis, providing new insights into the mechanism of action of the encoded proteins and in some cases into the defect underlying the disease. Recent technological developments have covered the genetic gap between mammals and non-mammalian model organisms, challenging the modelling role of the latter. Is there a future for Dictyostelium discoideum as a model organism?

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In Search of Species-Specific SNPs in a Non-Model Animal (European Bison (Bison bonasus))—Comparison of De Novo and Reference-Based Integrated Pipeline of STACKS Using Genotyping-by-Sequencing (GBS) Data

Animals ◽

10.3390/ani11082226 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2226

Author(s):

Sazia Kunvar ◽

Sylwia Czarnomska ◽

Cino Pertoldi ◽

Małgorzata Tokarska

Keyword(s):

Reference Genome ◽

De Novo ◽

Bos Taurus ◽

Model Organism ◽

Genotyping By Sequencing ◽

Model Organisms ◽

European Bison ◽

Model Animal ◽

Pcr Duplicates ◽

Species Specific

The European bison is a non-model organism; thus, most of its genetic and genomic analyses have been performed using cattle-specific resources, such as BovineSNP50 BeadChip or Illumina Bovine 800 K HD Bead Chip. The problem with non-specific tools is the potential loss of evolutionary diversified information (ascertainment bias) and species-specific markers. Here, we have used a genotyping-by-sequencing (GBS) approach for genotyping 256 samples from the European bison population in Bialowieza Forest (Poland) and performed an analysis using two integrated pipelines of the STACKS software: one is de novo (without reference genome) and the other is a reference pipeline (with reference genome). Moreover, we used a reference pipeline with two different genomes, i.e., Bos taurus and European bison. Genotyping by sequencing (GBS) is a useful tool for SNP genotyping in non-model organisms due to its cost effectiveness. Our results support GBS with a reference pipeline without PCR duplicates as a powerful approach for studying the population structure and genotyping data of non-model organisms. We found more polymorphic markers in the reference pipeline in comparison to the de novo pipeline. The decreased number of SNPs from the de novo pipeline could be due to the extremely low level of heterozygosity in European bison. It has been confirmed that all the de novo/Bos taurus and Bos taurus reference pipeline obtained SNPs were unique and not included in 800 K BovineHD BeadChip.

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Alliance of Genome Resources Portal: unified model organism research platform

Nucleic Acids Research ◽

10.1093/nar/gkz813 ◽

2019 ◽

Vol 48 (D1) ◽

pp. D650-D658 ◽

Cited By ~ 36

Author(s):

◽

Julie Agapite ◽

Laurent-Philippe Albou ◽

Suzi Aleksander ◽

Joanna Argasinska ◽

...

Keyword(s):

Gene Ontology ◽

Model Organism ◽

Model Organisms ◽

Data Types ◽

Primary Model ◽

Genomic Studies ◽

Health And Disease ◽

Extensive Body ◽

Access To Data ◽

Model Organism Databases

Abstract The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource.

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GC-TOF/MS-based metabolomics analysis to investigate the changes driven by N-Acetylcysteine in the plant-pathogen Xanthomonas citri subsp. citri

Scientific Reports ◽

10.1038/s41598-021-95113-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Simone Cristina Picchi ◽

Mariana de Souza e Silva ◽

Luiz Leonardo Saldanha ◽

Henrique Ferreira ◽

Marco Aurélio Takita ◽

...

Keyword(s):

Amino Acids ◽

Cell Proliferation ◽

Plant Pathogen ◽

Model Organism ◽

Citrus Canker ◽

Bacterial Cells ◽

Xanthomonas Citri ◽

Canker Disease ◽

Potential Use

AbstractN-Acetylcysteine (NAC) is an antioxidant, anti-adhesive, and antimicrobial compound. Even though there is much information regarding the role of NAC as an antioxidant and anti-adhesive agent, little is known about its antimicrobial activity. In order to assess its mode of action in bacterial cells, we investigated the metabolic responses triggered by NAC at neutral pH. As a model organism, we chose the Gram-negative plant pathogen Xanthomonas citri subsp. citri (X. citri), the causal agent of citrus canker disease, due to the potential use of NAC as a sustainable molecule against phytopathogens dissemination in citrus cultivated areas. In presence of NAC, cell proliferation was affected after 4 h, but damages to the cell membrane were observed only after 24 h. Targeted metabolite profiling analysis using GC–MS/TOF unravelled that NAC seems to be metabolized by the cells affecting cysteine metabolism. Intriguingly, glutamine, a marker for nitrogen status, was not detected among the cells treated with NAC. The absence of glutamine was followed by a decrease in the levels of the majority of the proteinogenic amino acids, suggesting that the reduced availability of amino acids affect protein synthesis and consequently cell proliferation.

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Stroke Genetics: Turning Discoveries into Clinical Applications

Stroke ◽

10.1161/strokeaha.121.032616 ◽

2021 ◽

Author(s):

Martin Dichgans ◽

Nathalie Beaufort ◽

Stephanie Debette ◽

Christopher D. Anderson

Keyword(s):

Mendelian Randomization ◽

Association Studies ◽

Clinical Applications ◽

Risk Scores ◽

Genome Wide Association Studies ◽

Neuroprotective Agents ◽

Experimental Systems ◽

Genome Wide ◽

Rapid Pace

The field of medical and population genetics in stroke is moving at a rapid pace and has led to unanticipated opportunities for discovery and clinical applications. Genome-wide association studies have highlighted the role of specific pathways relevant to etiologically defined subtypes of stroke and to stroke as a whole. They have further offered starting points for the exploration of novel pathways and pharmacological strategies in experimental systems. Mendelian randomization studies continue to provide insights in the causal relationships between exposures and outcomes and have become a useful tool for predicting the efficacy and side effects of drugs. Additional applications that have emerged from recent discoveries include risk prediction based on polygenic risk scores and pharmacogenomics. Among the topics currently moving into focus is the genetics of stroke outcome. While still at its infancy, this field is expected to boost the development of neuroprotective agents. We provide a brief overview on recent progress in these areas.

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