Use Of Model Organisms Research Articles

Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.

Mitochondria play a crucial role in maintaining the energy status and redox homeostasis of eukaryotic cells. They are responsible for the metabolic efficiency of cells, providing both ATP and intermediate metabolic products. They also regulate cell survival and death under stress conditions by controlling the cell response or activating the apoptosis process. This functional diversity of mitochondria indicates their great importance for cellular metabolism. Hence, dysfunctions of these structures are increasingly recognized as an element of the etiology of many human diseases and, therefore, an extremely promising therapeutic target. Mitochondrial dysfunctions can be caused by mutations in both nuclear and mitochondrial DNA, as well as by stress factors or replication errors. Progress in knowledge about the biology of mitochondria, as well as the consequences for the efficiency of the entire organism resulting from the dysfunction of these structures, is achieved through the use of model organisms. They are an invaluable tool for analyzing complex cellular processes, leading to a better understanding of diseases caused by mitochondrial dysfunction. In this work, we review the most commonly used model organisms, discussing both their advantages and limitations in modeling fundamental mitochondrial processes or mitochondrial diseases.

Variation to Biology: Optimizing Functional Analysis of Cancer Risk Variants.

Research conducted over the past 15+ years has identified hundreds of common germline genetic variants associated with cancer risk but understanding the biological impact of these primarily non-protein coding variants has been challenging [1]. The National Cancer Institute sought to better understand and address those challenges by requesting input from the scientific community via a survey and a 2-day virtual meeting, which focused on discussions among participants. Here, we discuss challenges identified through the survey as important to advancing functional analysis of common cancer risk variants: 1) When is a variant truly characterized; 2) Developing and standardizing databases and computational tools; 3) Optimization and implementation of high throughput assays; 4) Use of model organisms for understanding variant function; 5) Diversity in data and assays; and 6) Creating and improving large multidisciplinary collaborations. We define these six challenges, describe how success in addressing them may look, propose potential solutions, and note issues that span all the challenges. Implementation of these ideas could help develop a framework for methodically analyzing common cancer risk variants to understand their function and make effective and efficient use of the wealth of existing genomic association data.

Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections. To this end, Le Studium Institute of Advanced Studies organized a two-day conference to identify major gaps in our understanding of ascarid parasites with a view to setting research priorities that would allow for improved control. The participants identified several key areas for future focus, comprising of advances in genomic analysis and the use of model organisms, especially Caenorhabditis elegans, a more thorough appreciation of the complexity of host-parasite (and parasite-parasite) communications, a search for novel anthelmintic drugs and the development of effective vaccines. The participants agreed to try and maintain informal links in the future that could form the basis for collaborative projects, and to co-operate to organize future meetings and workshops to promote ascarid research.

Assessment of The Effect of Antidiarrheal Drugs and Plant Extracts on Drosophila melanogaster.

To study human gastrointestinal physiology, biomedical scientists have relied on the use of model organisms. Although many researchers have used mice as a model to study intestinal function, only a few reports have focused on Drosophila melanogaster (D. melanogaster). Compared to mice, fruit flies present many advantages, such as a short life cycle, cost-effective and simple maintenance, and no ethical issues. Furthermore, the mammalian gastrointestinal physiology, anatomy, and signaling pathways are highly conserved in D. melanogaster. Plant extracts have been used traditionally to treat diarrhea and constipation. For example, Psidium guajava (P. guajava) is one of the most known antidiarrheal agents in the tropics. However, no studies have evaluated the effect of antidiarrheal and laxative drugs and plant extracts in D. melanogaster, and it remains unknown if similar effects (e.g., smaller, more concentrated, and less abundant fecal deposits in the case of antidiarrheal drugs) can occur in the fruit flies compared to mammals. In this study, an antidiarrheal effect induced by P. guajava is demonstrated in a D. melanogaster strain that presents a diarrheic phenotype. Fecal sampling produced by flies is monitored using a dye-supplemented food. This protocol outlines the method used for preparing food with drugs, evaluating the fecal deposits of flies fed on these food preparations, and interpreting the data obtained.

Schmidtea mediterranea as a Model Organism to Study the Molecular Background of Human Motile Ciliopathies.

Cilia and flagella are evolutionarily conserved organelles that form protrusions on the surface of many growth-arrested or differentiated eukaryotic cells. Due to the structural and functional differences, cilia can be roughly classified as motile and non-motile (primary). Genetically determined dysfunction of motile cilia is the basis of primary ciliary dyskinesia (PCD), a heterogeneous ciliopathy affecting respiratory airways, fertility, and laterality. In the face of the still incomplete knowledge of PCD genetics and phenotype-genotype relations in PCD and the spectrum of PCD-like diseases, a continuous search for new causative genes is required. The use of model organisms has been a great part of the advances in understanding molecular mechanisms and the genetic basis of human diseases; the PCD spectrum is not different in this respect. The planarian model (Schmidtea mediterranea) has been intensely used to study regeneration processes, and-in the context of cilia-their evolution, assembly, and role in cell signaling. However, relatively little attention has been paid to the use of this simple and accessible model for studying the genetics of PCD and related diseases. The recent rapid development of the available planarian databases with detailed genomic and functional annotations prompted us to review the potential of the S. mediterranea model for studying human motile ciliopathies.

Establishing a model fish for the Neotropical region: The case of the yellowtail tetra Astyanax altiparanae in advanced biotechnology.

The use of model organisms is important for basic and applied sciences. Several laboratory species of fishes are used to develop advanced technologies, such as the zebrafish (Danio rerio), the medaka (Oryzias latipes), and loach species (Misgurnus spp.). However, the application of these exotic species in the Neotropical region is limited due to differences in environmental conditions and phylogenetic distances. This situation emphasizes the establishment of a model organism specifically for the Neotropical region with the development of techniques that may be applicable to other Neotropical fish species. In this work, the previous research efforts are described in order to establish the yellowtail tetra Astyanax altiparanae as a model laboratory species for both laboratory and aquaculture purposes. Over the last decade, starting with artificial fertilization, the yellowtail tetra has become a laboratory organism for advanced biotechnology, such as germ cell transplantation, chromosome set manipulation, and other technologies, with applications in aquaculture and conservation of genetic resources. Nowadays, the yellowtail tetra is considered the most advanced fish with respect to fish biotechnology within the Neotropical region. The techniques developed for this species are being used in other related species, especially within the characins class.

Sentinel species selection for monitoring microplastic pollution: A review on one health approach

Nowadays, global environmental pollution is one of the most topical issues we have to deal with on a daily basis. Due to the development of the current society including industrial and agricultural areas, pollution and waste have increased dramatically in recent years. Among all contaminants spread worldwide, the increased use of plastic is probably the most evident. Nevertheless, plastic objects which are released into environmental compartments are processed into smaller units of plastic debris, defined, based on their dimensions, as micro- (MP) and nano-plastics (NP). These particles are classified as some of the most hazardous current micro-pollutants. The use of model organisms as bioindicators is one of the most effective ways to monitor and assess the occurrence of plastic particles in the environment.This review aims to provide comprehensive knowledge about the behaviour and the effects of MP/NPs particles on animals, humans, and the environment through the “One Health” concept, which provides an innovative and suitable perspective focused on the intersection of the above-mentioned three areas. Moreover, the key point is the evaluation of the most efficient bioindicators for monitoring microplastic pollution in environmental compartments, in order to better understand the importance of being more eco-friendly through the reduction of plastics objects.Whereas the earth is composed of about 70% water, a special focus is placed on aquatic ecosystems and the relative bioindicators. In addition, this collection of information highlights a common issue that requires awareness, prevention, and solutions to take care of global environments.

Identification of Novel Regulators for GPCR‐signaling via Genome‐wide Analysis

G protein‐coupled receptors (GPCRs) are a large family of proteins responsible for receiving and responding to many signals such as smell, light, and hormones. GPCRs are also the target for approximately thirty‐four percent of all FDA approved drugs. Therefore, gaining new insight about GPCR signaling regulation can be useful for improving our understanding of cellular physiology and enhancing the effectiveness of the drugs we use. GPCR signaling is highly conserved, enabling the use of model organisms, such as budding yeast Saccharomyces cerevisiae, to study its regulation. Yeast responds to pheromone using a well‐characterized GPCR pathway. In this project, we screened a collection of yeast mutants that all had one gene deleted from their genome, using a well‐established assay that measures pheromone response. From this screen, we have identified seven novel mutants that clearly and consistently alter the pheromone response. Further analysis of these mutants indicates that some of them affect the pheromone response at the level of or upstream of MAP kinase Fus3. We are in the process of cloning these genes and examining if the abnormal pheromone response and Fus3 activation of these mutants can be rescued. Our analysis suggests that unbiased genome‐wide genetic screening remains a viable approach in identifying novel regulators for GPCR‐mediated signaling.

Zebrafish information network, the knowledgebase for Danio rerio research.

The Zebrafish Information Network (zfin.org) is the central repository for Danio rerio genetic and genomic data. The Zebrafish Information Network has served the zebrafish research community since 1994, expertly curating, integrating, and displaying zebrafish data. Key data types available at the Zebrafish Information Network include, but are not limited to, genes, alleles, human disease models, gene expression, phenotype, and gene function. The Zebrafish Information Network makes zebrafish research data Findable, Accessible, Interoperable, and Reusable through nomenclature, curatorial and annotation activities, web interfaces, and data downloads. Recently, the Zebrafish Information Network and 6 other model organism knowledgebases have collaborated to form the Alliance of Genome Resources, aiming to develop sustainable genome information resources that enable the use of model organisms to understand the genetic and genomic basis of human biology and disease. Here, we provide an overview of the data available at the Zebrafish Information Network including recent updates to the gene page to provide access to single-cell RNA sequencing data, links to Alliance web pages, ribbon diagrams to summarize the biological systems and Gene Ontology terms that have annotations, and data integration with the Alliance of Genome Resources.

The Neuroepigenetic Landscape of Vertebrate and Invertebrate Models of Neurodegenerative Diseases.

Vertebrate and invertebrate models of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, have been paramount to our understanding of the pathophysiology of these conditions; however, the brain epigenetic landscape is less well established in these disease models. DNA methylation, histone modifications, and microRNAs are among commonly studied mechanisms of epigenetic regulation. Genome-wide studies and candidate studies of specific methylation marks, histone marks, and microRNAs have demonstrated the dysregulation of these mechanisms in models of neurodegenerative diseases; however, the studies to date are scarce and inconclusive and the implications of many of these changes are still not fully understood. In this review, we summarize epigenetic changes reported to date in the brain of vertebrate and invertebrate models used to study neurodegenerative diseases, specifically diseases affecting the aging population. We also discuss caveats of epigenetic research so far and the use of disease models to understand neurodegenerative diseases, with the aim of improving the use of model organisms in this context in future studies.

Model Organisms for Studying Decision-Making: A Phylogenetically Expanded Perspective

This article explores the use of model organisms in studying the cognitive phenomenon of decision-making. Drawing on the framework of biological control to develop a skeletal conception of decision-making, we show that two core features of decision-making mechanisms can be identified by studying model organisms, such asE. coli, jellyfish,C. elegans, lamprey, and so on. First, decision mechanisms are distributed and heterarchically structured. Second, they depend heavily on chemical information processing, such as that involving neuromodulators. We end by discussing the implications for studying distinctively human decision-making.

Introducing nematodes and the use of model organisms: a practical class for undergraduate students

ABSTRACT Most undergraduate students do not have practical experience working with model organisms despite having theoretical knowledge of their importance. This practical was developed to offer students experience working with three species of nematode, including Caenorhabditis elegans. In the first task, students prepare slides of three previously fixed nematode samples and are asked to identify their feeding preferences based on information given to them in a short pre-practical presentation. The second and third tasks allow students to deduce the existence of a functional nervous system in Caenorhabditis elegans and then to measure the response of two genotypes, N2 and slo-1, to different concentrations of an ethanol solution. These tasks demonstrate the heterogeneity of different nematodes and enable students to gain experience in widely applicable skills including microscopy, slide preparation, assay design and data presentation. Students also gain experience in specialised skills such as worm picking, which is essential in Caenorhabditis elegans research. This practical can be completed as a standalone and would suit any early year biology course.

A guide to changing paradigms of glucocorticoid receptor function-a model system for genome regulation and physiology.

The glucocorticoid receptor (GR) is a bona fide ligand-regulated transcription factor. Cloned in the 80s, the GR has become one of the best-studied and clinically most relevant members of the nuclear receptor superfamily. Cooperative activity of GR with other transcription factors and a plethora of coregulators contribute to the tissue- and context-specific response toward the endogenous and pharmacological glucocorticoids (GCs). Furthermore, nontranscriptional activities in the cytoplasm are emerging as an additional function of GR. Over the past 40years, the concepts of GR mechanisms of action had been constantly changing. Different methodologies in the pregenomic and genomic era of molecular biological research and recent cutting-edge technology in single-cell and single-molecule analysis are steadily evolving the views, how the GR in particular and transcriptional regulation in general act in physiological and pathological processes. In addition to the development of technologies for GR analysis, the use of model organisms provides insights how the GR invivo executes GC action in tissue homeostasis, inflammation, and energy metabolism. The model organisms, namely the mouse, but also rats, zebrafish, and recently fruit flies carrying mutations of the GR became a major driving force to analyze the molecular function of GR in disease models. This guide provides an overview of the exciting research and paradigm shifts in the GR field from past to present with a focus on GR transcription factor networks, GR DNA-binding and single-cell analysis, and model systems.

CGAS-STING: insight on the evolution of a primordial antiviral signaling cassette.

Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2′3′-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. We review here recent advances in the remarkable history of cGAS-STING signaling, which establish that cGAS is a member of the family of cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize a wide range of cyclic oligonucleotide second messengers in response to bacteriophage infections, which in turn activate a variety of effector proteins to abort phage infection. Among these effectors, some are related to STING, revealing an ancestral function for the cGAS-STING cassette in antiviral host defense. Study of STING signaling in invertebrate animals is consistent with an early acquisition in the history of metazoans of CD-NTase- and STING-encoding genes to counter the universal threat of viruses. In particular, STING-dependent immunity appears to play a previously unsuspected important role in some insects. These discoveries open up interesting perspectives for the use of model organisms to decipher emerging aspects of cGAS-STING biology in mammals, such as the activation of interferon-independent responses or the function and regulation of cGAS in the nucleus.

Model Organisms in Cancer Research-Powers and Limitations

Background: Cancer is a term that is used to describe a wide range of diseases, but they all have some characteristics in common. The goal of this review is to highlight the most commonly used cancer models as well as their role in tumor biology. Although each model has inherent powers and limitations in faithfully mirroring the complexity of tumorigenesis, there is no perfect single model for cancer. Main body: Oncologists can learn about the tumor microenvironment, gene mutations, and complex physiological systems using model organisms for cancer research. The widespread use of model organisms in cancer research has greatly improved understanding of how mutations in humans lead to cancer. Human cancer cell lines, drosophila, yeast, and mice are among the model organisms used to study cancer. However, these model organisms have flaws that can cause the tumor microenvironment to be falsified and restrict the defined targets in translational studies. Conclusion: The overwhelming message from various animal models allows us to better understand the state of the disease and develop new cancer treatments. Mice are a good substitute and surrogate for patients in the evaluation of diagnosis and prognosis among the various model organisms used in cancer research.

The Making of Long-Lasting Memories: A Fruit Fly Perspective

Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.

Multi-omic and multi-species meta-analyses of nicotine consumption

Cross-species translational approaches to human genomic analyses are lacking. The present study uses an integrative framework to investigate how genes associated with nicotine use in model organisms contribute to the genetic architecture of human tobacco consumption. First, we created a model organism geneset by collecting results from five animal models of nicotine exposure (RNA expression changes in brain) and then tested the relevance of these genes and flanking genetic variation using genetic data from human cigarettes per day (UK BioBank N = 123,844; all European Ancestry). We tested three hypotheses: (1) DNA variation in, or around, the ‘model organism geneset’ will contribute to the heritability to human tobacco consumption, (2) that the model organism genes will be enriched for genes associated with human tobacco consumption, and (3) that a polygenic score based off our model organism geneset will predict tobacco consumption in the AddHealth sample (N = 1667; all European Ancestry). Our results suggested that: (1) model organism genes accounted for ~5–36% of the observed SNP-heritability in human tobacco consumption (enrichment: 1.60–31.45), (2) model organism genes, but not negative control genes, were enriched for the gene-based associations (MAGMA, H-MAGMA, SMultiXcan) for human cigarettes per day, and (3) polygenic scores based on our model organism geneset predicted cigarettes per day in an independent sample. Altogether, these findings highlight the advantages of using multiple species evidence to isolate genetic factors to better understand the etiological complexity of tobacco and other nicotine consumption.

Noble Crayfish Are More Sensitive to Terbuthylazine than Parthenogenetic Marbled Crayfish

We investigated the sensitivity of two freshwater crayfish species (Astacus astacus and Procambarus virginalis) during embryonic development to chronic exposure to the herbicide terbuthylazine under laboratory conditions. The assessed parameters included time of embryonic development, survival rate, hatching weight and histopathology of hepatopancreas. LC50 (median lethal concentration) and ED50 (median effective concentration) were estimated. We were able to determine effects of terbuthylazine for every investigated parameter. For noble crayfish, the LC50 value after 45 days was 0.11 mg/L, and the histology of the hepatopancreas showed effects starting from 0.025 mg/L. Other parameters revealed effects starting at concentrations of 1.6 mg/L for weight and 6.4 mg /L for embryonic development time and hatching rate. Marbled crayfish only showed effects concerning the hatching rate and survival rate at concentrations without a clear dose-effects curve. As a conclusion, our data shows the risk of terbuthylazine in existing concentrations in freshwater ecosystems to non-target organisms and also the need of toxicological studies on directly affected species in addition to the use of model organisms.

Animal models of sarcopenia.

Sarcopenia is the age‐related decline in muscle mass and function without any underlying disease. The exact molecular mechanisms responsible for this pathology remain unknown. The use of model organisms, such as mice, rats, flies, and worms, has advanced the field of sarcopenia research by identifying therapeutic strategies and genetic mutations that result in improved muscle mass and function of elderly animals. This review discusses molecular and therapeutic discoveries made using these model organisms and how these animals can be further utilized to better understand sarcopenia pathogenesis. In rodents, flies, and worms, dietary restriction improves muscle performance in old animals. In rodents and worms, exercise and a number of naturally occurring compounds alleviate sarcopenia. Reduction in the insulin/IGF1 receptor pathway, well known to promote longevity, improves sarcopenia in worms and flies. Mitochondrial dysfunction may contribute to the pathogenesis of sarcopenia: In rodents, there is age‐dependent reduction in mitochondrial mass and a change in morphology; in nematodes, there is age‐dependent fragmentation of mitochondria that precedes sarcomeric disorganization. In Drosophila and rats, components of the 26S proteasome are elevated in aged muscle. An advantage of the worm and fly models is that these organisms lack muscle stem cells, and thus processes that promote the maintenance of already assembled muscle, can be identified without the confounding influence of muscle regeneration. Zebrafish are an up and coming model of sarcopenia for future consideration. A better understanding of the molecular changes behind sarcopenia will help researchers develop better therapies to improve the muscle health of elderly individuals.

Host expression system modulates recombinant Hsp70 activity through post-translational modifications.

The use of model organisms for recombinant protein production results in the addition of model-specific post-translational modifications (PTMs) that can affect the structure, charge, and function of the protein. The 70-kDa heat shock proteins (Hsp70) were originally described as intracellular chaperones, with ATPase and foldase activity. More recently, new extracellular activities of Hsp70 proteins (e.g. as immunomodulators) have been identified. While some studies indicate an inflammatory potential for extracellular Hsp70 proteins, others suggest an immunosuppressive activity. We hypothesized that the production of recombinant Hsp70 in different expression systems would result in the addition of different PTMs, perhaps explaining at least some of these opposing immunological outcomes. We produced and purified Mycobacterium tuberculosis DnaK from two different systems, Escherichia coli and Pichia pastoris, and analyzed by mass spectrometry the protein preparations, investigating the impact of PTMs in an in silico and in vitro perspective. The comparisons of DnaK structures in silico highlighted that electrostatic and topographical differences exist that are dependent upon the expression system. Production of DnaK in the eukaryotic system dramatically affected its ATPase activity, and significantly altered its ability to downregulate MHC II and CD86 expression on murine dendritic cells (DCs). Phosphatase treatment of DnaK indicated that some of these differences related specifically to phosphorylation. Altogether, our data indicate that PTMs are an important characteristic of the expression system, with differences that impact interactions of Hsps with their ligands and subsequent functional activities.