scholarly journals New Roles for Model Genetic Organisms in Understanding and Treating Human Disease: Report From The 2006 Genetics Society of America Meeting

Genetics ◽  
2006 ◽  
Vol 172 (4) ◽  
pp. 2025-2032
Author(s):  
Allan Spradling ◽  
Barry Ganetsky ◽  
Phil Hieter ◽  
Mark Johnston ◽  
Maynard Olson ◽  
...  
Keyword(s):  
Human Disease ◽  
Medical Science ◽  
Genetic Research ◽  
Model Organism ◽  
Model Systems ◽  
Neurological Dysfunction ◽  
Model Organisms ◽  
Biological Knowledge ◽  
Medical Disorders ◽  
The Future

Abstract Fundamental biological knowledge and the technology to acquire it have been immeasurably advanced by past efforts to understand and manipulate the genomes of model organisms. Has the utility of bacteria, yeast, worms, flies, mice, plants, and other models now peaked and are humans poised to become the model organism of the future? The Genetics Society of America recently convened its 2006 meeting entitled “Genetic Analysis: Model Organisms to Human Biology” to examine the future role of genetic research. (Because of time limitations, the meeting was unable to cover the substantial contributions and future potential of research on model prokaryotic organisms.) In fact, the potential of model-organism-based studies has grown substantially in recent years. The genomics revolution has revealed an underlying unity between the cells and tissues of eukaryotic organisms from yeast to humans. No uniquely human biological mechanisms have yet come to light. This common evolutionary heritage makes it possible to use genetically tractable organisms to model important aspects of human medical disorders such as cancer, birth defects, neurological dysfunction, reproductive failure, malnutrition, and aging in systems amenable to rapid and powerful experimentation. Applying model systems in this way will allow us to identify common genes, proteins, and processes that underlie human medical conditions. It will allow us to systematically decipher the gene–gene and gene–environment interactions that influence complex multigenic disorders. Above all, disease models have the potential to address a growing gap between our ability to collect human genetic data and to productively interpret and apply it. If model organism research is supported with these goals in mind, we can look forward to diagnosing and treating human disease using information from multiple systems and to a medical science built on the unified history of life on earth.

scholarly journals An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models

2022 ◽  
Vol 9 ◽  
Author(s):  
Timothy J. Hines ◽  
Cathleen Lutz ◽  
Stephen A. Murray ◽  
Robert W. Burgess
Keyword(s):  
Human Disease ◽  
Neuromuscular Diseases ◽  
Trna Synthetase ◽  
Genetically Engineered ◽  
Model Systems ◽  
Model Organisms ◽  
Cellular Mechanisms ◽  
Disease Mechanisms

As sequencing technology improves, the identification of new disease-associated genes and new alleles of known genes is rapidly increasing our understanding of the genetic underpinnings of rare diseases, including neuromuscular diseases. However, precisely because these disorders are rare and often heterogeneous, they are difficult to study in patient populations. In parallel, our ability to engineer the genomes of model organisms, such as mice or rats, has gotten increasingly efficient through techniques such as CRISPR/Cas9 genome editing, allowing the creation of precision human disease models. Such in vivo model systems provide an efficient means for exploring disease mechanisms and identifying therapeutic strategies. Furthermore, animal models provide a platform for preclinical studies to test the efficacy of those strategies. Determining whether the same mechanisms are involved in the human disease and confirming relevant parameters for treatment ideally involves a human experimental system. One system currently being used is induced pluripotent stem cells (iPSCs), which can then be differentiated into the relevant cell type(s) for in vitro confirmation of disease mechanisms and variables such as target engagement. Here we provide a demonstration of these approaches using the example of tRNA-synthetase-associated inherited peripheral neuropathies, rare forms of Charcot-Marie-Tooth disease (CMT). Mouse models have led to a better understanding of both the genetic and cellular mechanisms underlying the disease. To determine if the mechanisms are similar in human cells, we will use genetically engineered iPSC-based models. This will allow comparisons of different CMT-associated GARS alleles in the same genetic background, reducing the variability found between patient samples and simplifying the availability of cell-based models for a rare disease. The necessity of integrating mouse and human models, strategies for accomplishing this integration, and the challenges of doing it at scale are discussed using recently published work detailing the cellular mechanisms underlying GARS-associated CMT as a framework.

scholarly journals OMAMO: orthology-based model organism selection

2021 ◽  
Author(s):  
Alina Nicheperovich ◽  
Adrian M Altenhoff ◽  
Christophe Dessimoz ◽  
Sina Majidian
Keyword(s):  
Literature Review ◽  
Biological Process ◽  
Model Organism ◽  
Complex Model ◽  
Model Systems ◽  
Human Model ◽  
Model Organisms ◽  
Human Biology ◽  
Traditional Model ◽  
Ethical Concerns

The conservation of pathways and genes across species has allowed scientists to use non-human model organisms to gain a deeper understanding of human biology. However, the use of traditional model systems such as mice, rats, and zebrafish is costly, time-consuming and increasingly raises ethical concerns, which highlights the need to search for less complex model organisms. Existing tools only focus on the few well-studied model systems, most of which are higher animals. To address these issues, we have developed Orthologous Matrix and Model Organisms, a software and a website that provide the user with the best simple organism for research into a biological process of interest based on orthologous relationships between the human and the species. The outputs provided by the database were supported by a systematic literature review.

scholarly journals Honey bee as an alternative model invertebrate organism

2025 ◽  
Vol 74 (10) ◽  
pp. 6140-2025
Author(s):  
ALEKSANDRA ŁOŚ ◽  
MAŁGORZATA BIEŃKOWSKA ◽  
ANETA STRACHECKA
Keyword(s):  
Collective Intelligence ◽  
Lethal Dose ◽  
Genetic Research ◽  
Model Organism ◽  
Model Organisms ◽  
Cellular Mechanisms ◽  
Bee Colony ◽  
Proboscis Extension ◽  
The Individual ◽  
Explosive Devices

Insects perfectly fit the flagship principle of animal research – 3R: to reduce (the number of animals), to replace (animals with alternative models) and to refine (methods). Bees have the most important advantages of a model organism: they cause minimal ethical controversy, they have a small and fully known genome, and they permit the use of many experimental techniques. Bees have a fully functional DNMT toolkit. Therefore, they are used as models in biomedical/genetic research, e.g. in research on the development of cancer or in the diagnostics of mental and neuroleptic diseases in humans. The reversion of aging processes in bees offers hope for progress in gerontology research. The cellular mechanisms of learning and memory coding, as well as the indicators of biochemical immunity parameters, are similar or analogous to those in humans, so bees may become useful in monitoring changes in behavior and metabolism. Bees are very well suited for studies on the dose of the substance applied to determine the lethal dose or the effect of a formula on life expectancy. Honeybees have proven to be an effective tool for studying the effects of a long-term consumption of stimulants, as well as for observing behavioral changes and developing addictions at the individual and social levels, as well as for investigating the effects of continuously delivering the same dose of a substance. The genomic and physiological flexibility of bees in dividing tasks among workers in a colony makes it possible to create a Single- Cohort Colony (SCC) in which peers compared perform different tasks. Moreover behavioral methods (e.g. Proboscis Extension Reflex – PER, Sting Extension Reflex – SER, free flying target discrimination tasks or the cap pushing response) make it possible to analyse changes occurring in honeybee brains during learning and remembering. Algorithms of actions are created based on the behavior of a colony or individual, e.g. Artificial Bee Colony Algorithm (ABCA). Honeybees are also model organisms for profiling the so-called intelligence of a swarm or collective intelligence. Additionally, they serve as models for guidance systems and aviation technologies. Bees have inspired important projects in robotics, such as B-droid, Robobee and The Green Brain Project. It has also been confirmed that the apian sense of smell can be used to detect explosive devices, such as TNT, or drugs (including heroin, cocaine, amphetamines and cannabis). This inconspicuous little insect can revolutionize the world of science and contribute to the solution of many scientific problems as a versatile model.

scholarly journals Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1303
Author(s):  
Tiziana Cervelli ◽  
Alvaro Galli
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Variability ◽  
Human Disease ◽  
Human Genetics ◽  
Model Organism ◽  
Model Organisms ◽  
Gene Variants ◽  
Yeast Saccharomyces Cerevisiae ◽  
Next Generation Dna Sequencing ◽  
Sequencing Technologies

At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due to its genetic tractability, the yeast Saccharomyces cerevisiae represents a valuable model organism for understanding human genetic variability. In the present review, we show how S. cerevisiae has been used to study variants of genes involved in different diseases and in different pathways, highlighting the versatility of this model organism.

scholarly journals An Electrochemical Investigation of Interfacial Electron Uptake by the Sulfur Oxidizing Bacterium Thioclava electrotropha ElOx9

2019 ◽  
Author(s):  
Amruta Karbelkar ◽  
Annette R Rowe ◽  
Moh El-Naggar
Keyword(s):  
Microbial Fuel Cells ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Sulfur Oxidation ◽  
Model Systems ◽  
Model Organisms ◽  
Extracellular Electron Transfer ◽  
Solid State Electron ◽  
Marine Microbe ◽  
Sulfur Oxidizing

Extracellular electron transfer (EET) allows microbes to acquire energy from solid state electron acceptors and donors, such as environmental minerals. This process can also be harnessed at electrode interfaces in bioelectrochemical technologies including microbial fuel cells, microbial electrosynthesis, bioremediation, and wastewater treatment. Improving the performance of these technologies will benefit from a better fundamental understanding of EET in diverse microbial systems. While the mechanisms of outward (i.e. microbe-to-anode) EET is relatively well characterized, specifically in a few metal-reducing bacteria, the reverse process of inward EET from redox-active minerals or cathodes to bacteria remains poorly understood. This knowledge gap stems, at least partly, from the lack of well-established model organisms and general difficulties associated with laboratory studies in existing model systems. Recently, a sulfur oxidizing marine microbe, <i>Thioclava electrotropha</i> ElOx9, was demonstrated to perform electron uptake from cathodes. However, a detailed analysis of the electron uptake pathways has yet to be established, and electrochemical characterization has been limited to aerobic conditions. Here, we report a detailed amperometric and voltammetric characterization of ElOx9 cells coupling cathodic electron uptake to reduction of nitrate as the sole electron acceptor. We demonstrate that this inward EET by ElOx9 is facilitated by a direct-contact mechanism through a redox center with a formal potential of -94 mV vs SHE, rather than soluble intermediate electron carriers. In addition to the implications for understanding microbial sulfur oxidation in marine environments, this study highlights the potential for ElOx9 to serve as a convenient and readily culturable model organism for understanding the molecular mechanisms of inward EET.

scholarly journals An Electrochemical Investigation of Interfacial Electron Uptake by the Sulfur Oxidizing Bacterium Thioclava electrotropha ElOx9

2019 ◽  
Author(s):  
Amruta Karbelkar ◽  
Annette R Rowe ◽  
Moh El-Naggar
Keyword(s):  
Microbial Fuel Cells ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Sulfur Oxidation ◽  
Model Systems ◽  
Model Organisms ◽  
Extracellular Electron Transfer ◽  
Solid State Electron ◽  
Marine Microbe ◽  
Sulfur Oxidizing

Extracellular electron transfer (EET) allows microbes to acquire energy from solid state electron acceptors and donors, such as environmental minerals. This process can also be harnessed at electrode interfaces in bioelectrochemical technologies including microbial fuel cells, microbial electrosynthesis, bioremediation, and wastewater treatment. Improving the performance of these technologies will benefit from a better fundamental understanding of EET in diverse microbial systems. While the mechanisms of outward (i.e. microbe-to-anode) EET is relatively well characterized, specifically in a few metal-reducing bacteria, the reverse process of inward EET from redox-active minerals or cathodes to bacteria remains poorly understood. This knowledge gap stems, at least partly, from the lack of well-established model organisms and general difficulties associated with laboratory studies in existing model systems. Recently, a sulfur oxidizing marine microbe, <i>Thioclava electrotropha</i> ElOx9, was demonstrated to perform electron uptake from cathodes. However, a detailed analysis of the electron uptake pathways has yet to be established, and electrochemical characterization has been limited to aerobic conditions. Here, we report a detailed amperometric and voltammetric characterization of ElOx9 cells coupling cathodic electron uptake to reduction of nitrate as the sole electron acceptor. We demonstrate that this inward EET by ElOx9 is facilitated by a direct-contact mechanism through a redox center with a formal potential of -94 mV vs SHE, rather than soluble intermediate electron carriers. In addition to the implications for understanding microbial sulfur oxidation in marine environments, this study highlights the potential for ElOx9 to serve as a convenient and readily culturable model organism for understanding the molecular mechanisms of inward EET.

scholarly journals Eastern red-backed salamanders: A comprehensive review of an undervalued model in evolution, ecology, & behavior

2021 ◽  
Author(s):  
M. Caitlin Fisher-Reid ◽  
Kristine Grayson ◽  
Sara R. Grouleff ◽  
Madelyn A. Hair ◽  
Tanya J. Hawley Matlaga ◽  
...  
Keyword(s):  
Collaborative Research ◽  
Model Organism ◽  
Plethodon Cinereus ◽  
Model Systems ◽  
Inclusive Development ◽  
Research Network ◽  
Model Organisms ◽  
Future Directions ◽  
Comprehensive Review ◽  
And Behavior

What makes a model organism? Identifying the qualities of a model organism has been given a great deal of attention in the biomolecular sciences, but less so in the fields of evolution, ecology, and behavior (EEB). In EEB, biotic and abiotic variation are features to understand, not bugs to get rid of, and EEB scientists often select organisms to study which best suit the scientific question at hand. Successful EEB model organisms can be studied at multiple biological scales and have a wealth of accumulated knowledge on which current research programs build. A recent call within EEB to invest in the inclusive development of diverse model systems and scientists has led us to evaluate the standing of the widespread, abundant, terrestrial salamander we study, the eastern red-backed salamander (Plethodon cinereus). We first look at salamanders as EEB models more generally, to determine where P. cinereus fits in this broader context. We next present a comprehensive review of the literature on the eastern red-backed salamander (Plethodon cinereus) since the last comprehensive review was completed in 1998. The core of our paper reviews 410 recent studies and highlights inconsistencies, gaps in our knowledge, and future directions in the context of the 1998 review. Finally, we present a collaborative research network, SPARCnet, as a nascent infrastructure for continued research on P. cinereus. Here, we especially discuss how this type of infrastructure can be broadly applied not just to other salamanders, but to other model systems, so that the future of EEB research may benefit from models which accurately represent, in Darwin’s words, “endless forms most beautiful and most wonderful.”

Model systems inform rare disease diagnosis, therapeutic discovery and pre-clinical efficacy

2019 ◽  
Vol 3 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Adebola Enikanolaiye ◽  
Monica J. Justice
Keyword(s):  
Rare Disease ◽  
Genetic Diagnosis ◽  
Model Organism ◽  
Basic Research ◽  
Disease Diagnosis ◽  
Disease Suppression ◽  
Model Systems ◽  
Model Organisms ◽  
Chemical Screening ◽  
Entry Points

Abstract Model systems have played a large role in understanding human diseases and are instrumental in taking basic research findings to the clinic; however, for rare diseases, model systems play an even larger role. Here, we outline how model organisms are crucial for confirming causal associations, understanding functional mechanisms and developing therapies for disease. As diseases that have been studied extensively through genetics and molecular biology, cystic fibrosis and Rett syndrome are portrayed as primary examples of how genetic diagnosis, model organism development and therapies have led to improved patient health. Considering which model to use, yeast, worms, flies, fish, mice or larger animals requires a careful evaluation of experimental genetic tools and gene pathway conservation. Recent advances in genome editing will aid in confirming diagnoses and developing model systems for rare disease. Genetic or chemical screening for disease suppression may reveal functional pathway members and provide candidate entry points for developing therapies. Model organisms may also be used in drug discovery and as preclinical models as a prelude to testing treatments in patient populations. Now, model organisms will increasingly be used as platforms for understanding variation in rare disease severity and onset, thereby informing therapeutic intervention.

The future of model organisms in human disease research

2011 ◽  
Vol 12 (8) ◽  
pp. 575-582 ◽  
Author(s):  
Timothy J. Aitman ◽  
Charles Boone ◽  
Gary A. Churchill ◽  
Michael O. Hengartner ◽  
Trudy F. C. Mackay ◽  
...  
Keyword(s):  
Human Disease ◽  
Model Organisms ◽  
Disease Research ◽  
The Future

scholarly journals A novel workflow to improve multi-locus genotyping of wildlife species: an experimental set-up with a known model system

2019 ◽  
Author(s):  
Mark A.F. Gillingham ◽  
B. Karina Montero ◽  
Kerstin Wihelm ◽  
Kara Grudzus ◽  
Simone Sommer ◽  
...  
Keyword(s):  
Sequence Data ◽  
Model Organism ◽  
Model Systems ◽  
Model Organisms ◽  
Amplification Efficiency ◽  
Amplification Bias ◽  
Link Type ◽  
Multiple Loci ◽  
Number Variation ◽  
Set Up

ABSTRACTGenotyping novel complex multigene systems is particularly challenging in non-model organisms. Target primers frequently amplify simultaneously multiple loci leading to high PCR and sequencing artefacts such as chimeras and allele amplification bias. Most next-generation sequencing genotyping pipelines have been validated in non-model systems whereby the real genotype is unknown and the generation of artefacts may be highly repeatable. Further hindering accurate genotyping, the relationship between artefacts and copy number variation (CNV) within a PCR remains poorly described. Here we investigate the latter by experimentally combining multiple known major histocompatibility complex (MHC) haplotypes of a model organism (chicken, Gallus gallus, 43 artificial genotypes with 2-13 alleles per amplicon). In addition to well defined “optimal” primers, we simulated a non-model species situation by designing “naive” primers, with sequence data from closely related Galliform species. We applied a novel open-source genotyping pipeline (ACACIA) to the data, and compared its performance with another, previously published, pipeline. ACACIA yielded very high allele calling accuracy (>98%). Non-chimeric artefacts increased linearly with increasing CNV but chimeric artefacts leveled when amplifying more than 4-6 alleles. As expected, we found heterogeneous amplification efficiency of allelic variants when co-amplifying multiple loci. Using our validated ACACIA pipeline and the example data of this study, we discuss in detail the pitfalls researchers should avoid in order to reliably genotype complex multigene systems. ACACIA and the datasets used in this study are publicly available at GitLab and FigShare (https://gitlab.com/psc_santos/ACACIAandhttps://figshare.com/projects/ACACIA/66485).

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