scholarly journals The rise to dominance of genetic model organisms and the decline of curiosity-driven organismal research

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243088
Author(s):  
Sarah M. Farris
Keyword(s):  
Biological Sciences ◽  
Genetic Model ◽  
Model Organism ◽  
National Institutes Of Health ◽  
Model Organisms ◽  
Biological Research ◽  
Health It ◽  
Living Things ◽  
Evolutionary Context ◽  
Diversity Of Life

Curiosity-driven, basic biological research “…performed without thought of practical ends…” establishes fundamental conceptual frameworks for future technological and medical breakthroughs. Traditionally, curiosity-driven research in biological sciences has utilized experimental organisms chosen for their tractability and suitability for studying the question of interest. This approach leverages the diversity of life to uncover working solutions (adaptations) to problems encountered by living things, and evolutionary context as to the extent to which these solutions may be generalized to other species. Despite the well-documented success of this approach, funding portfolios of United States granting agencies are increasingly filled with studies on a few species for which cutting-edge molecular tools are available (genetic model organisms). While this narrow focus may be justified for biomedically-focused funding bodies such as the National Institutes of Health, it is critical that robust federal support for curiosity-driven research using diverse experimental organisms be maintained by agencies such as the National Science Foundation. Using the disciplines of neurobiology and behavioral research as an example, this study finds that NSF grant awards have declined in association with a decrease in the proportion of grants funded for experimental, rather than genetic model organism research. The decline in use of experimental organisms in the literature mirrors but predates the shift grant funding. Today’s dominance of genetic model organisms was thus initiated by researchers themselves and/or by publication peer review and editorial preferences, and was further reinforced by pressure from granting agencies, academic employers, and the scientific community.

Ontogenetic development of the otic region in the new model organism, Leucoraja erinacea (Chondrichthyes; Rajidae)

2018 ◽  
Vol 109 (1-2) ◽  
pp. 105-114 ◽  
Author(s):  
Cathrin PFAFF ◽  
Jürgen KRIWET ◽  
Kyle MARTIN ◽  
Zerina JOHANSON
Keyword(s):  
Soft Tissues ◽  
Developmental Stages ◽  
Model Organism ◽  
Model Organisms ◽  
Biological Research ◽  
Developmental Studies ◽  
Micro Computed Tomography ◽  
Computed Tomography Scanning ◽  
Cartilaginous Fishes ◽  
Tomography Scanning

ABSTRACTCartilaginous fishes have a long evolutionary history dating back 440 million years and include model organisms in a number of fields of biological research. However, comparative developmental studies of these organisms, particularly neuroanatomical investigations, still remain sparse. Here, pre-hatching to adult developmental stages of the Little Skate, Leucoraja erinacea, are investigated using micro-computed tomography scanning in conjunction with staining procedures designed to improve visualisation of soft tissues. Within the ear, the anatomy of the skeletal labyrinth changes during ontogeny and differs substantially from the underlying membranous system, contrary to previous observations in sharks. Additionally, substantial morphological remodelling characterises the parietal fossa, which appears initially as a massive and hook-like structure and subsequently becomes slender and surrounded by soft tissue. The sizes of the vestibular system and neurocranium increase isometrically from pre- to post-hatching phases, and then exponentially after the post-hatching stages.

scholarly journals Rest Is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

2021 ◽  
Vol 15 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Yungyi Hsiao ◽  
Jeffrey B. Liu ◽  
Robert Huber ◽  
Leslie C. Griffith
Keyword(s):  
Operant Conditioning ◽  
Molecular Mechanisms ◽  
Genetic Model ◽  
Model Organism ◽  
Fruit Fly ◽  
Model Organisms ◽  
Valuable Insight ◽  
Reward Contingency ◽  
Neural Basis ◽  
Operant Task

Maladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. In the paradigm, flies walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, they receive a sucrose reward at the end of the hallway. Only flies that rest early in training learn the reward contingency normally. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced sleep does not promote learning, indicating that sleep itself is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning-impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.

scholarly journals A Genome for the Environment

2017 ◽  
Author(s):  
Dieter Ebert
Keyword(s):  
Phenotypic Plasticity ◽  
Natural History ◽  
Germ Cells ◽  
Model System ◽  
National Institutes Of Health ◽  
Model Systems ◽  
Model Organisms ◽  
Biological Research ◽  
System P ◽  
A Genome

Water fleas of the genus Daphnia are among the oldest model systems in biological research. Today, we know more about their natural history and ecology than of any other taxon. The Daphnia model also has left a notable mark on other fields. élie Metchnikoff used Daphnia to test his 1908 Nobel prize–winning idea that macrophages attack invading parasites as part of cellular immunity. August Weismann's studies of water fleas were instrumental in developing his theory that only germ cells transmit heritable information in animals. Richard Woltereck used Daphnia to develop the notion of phenotypic plasticity—that an organism can change its characteristics in response to the environment—an idea that still guides experiments with many organisms that distinguish genetic from environmental effects. With all of these historical achievements, why did the National Institutes of Health (NIH) only recently add Daphnia to its list of model organisms for biomedical research? Moreover, why has Daphnia, at this point in time, become NIH's 13th model system?

Evolution and Systematics

1999 ◽  
Vol 9 ◽  
pp. 95-118
Author(s):  
Sandra J. Carlson
Keyword(s):  
Biological Process ◽  
Vast Number ◽  
Common Descent ◽  
Living Things ◽  
Geological Past ◽  
Evolutionary Context ◽  
Similarity And Difference ◽  
Life On Earth ◽  
Diversity Of Life

The biological process of evolution – descent with modification – generates and structures the remarkable diversity of life on Earth today and in the geological past. Take a moment to consider the vast number of different kinds of living things: mushrooms, koalas, sunflowers, whales, mosquitoes, kelp, bacteria, tapeworms, lichens, clams, redwoods,…. the list could go on and on, seemingly forever. Without some understanding of how the diversity of life was generated, the scope of the diversity may seem overwhelming, perhaps even unknowable. Fortunately the structure of this extraordinary diversity, generated by the process of evolution, can be discovered using the methods of systematics. Evolution can be thought of as “an axiom from which systematic methods and concepts are deduced” (de Queiroz, 1988). Systematics, therefore, provides a way to organize the diversity surrounding us, and make sense of it in an evolutionary framework. Patterns of similarity and difference in morphology, genetics, and development — the evidence of evolution — can only be explained in an evolutionary context by means of systematics. No other method seeks to identify patterns that are evolutionary in origin, generated by the process of common descent.

scholarly journals Molecular characterization of frog vocal neurons using constellation pharmacology

2020 ◽  
Author(s):  
Ryota Thomas Inagaki ◽  
Shrinivasan Raghuraman ◽  
Kevin Chase ◽  
Theresa Steele ◽  
Erik Zornik ◽  
...  
Keyword(s):  
Genetic Model ◽  
Ex Vivo ◽  
Model Organism ◽  
Neuronal Cell ◽  
Model Organisms ◽  
Neural Basis ◽  
Specific Expression ◽  
Vocal Production ◽  
Similar Frequency

Identification and characterization of neuronal cell classes in motor circuits are essential for understanding the neural basis of behavior. It is a challenging task, especially in a non-genetic model organism, to identify cell-specific expression of functional macromolecules. Here, we performed constellation pharmacology, calcium imaging of dissociated neurons to pharmacologically identify functional receptors expressed by vocal neurons in adult male and female African clawed frogs, Xenopus laevis. Previously we identified a population of vocal neurons called fast trill neurons (FTNs) in the amphibian parabrachial nucleus (PB) that express NMDA receptors and GABA and/or glycine receptors. Using constellation pharmacology, we identified four cell classes of putative fast trill neurons (pFTNs, responsive to both NMDA and GABA/glycine applications). We discovered that some pFTNs responded to the application of substance P (SP), acetylcholine (ACh), or both. Electrophysiological recordings obtained from FTNs using an ex vivo preparation verified that SP and/or ACh depolarize FTNs. Bilateral injection of ACh, SP, or their antagonists into PBs showed that ACh receptors are not sufficient but necessary for vocal production, and SP receptors play a role in shaping the morphology of vocalizations. Additionally, we discovered that the PB of adult female X. laevis also contains all the subclasses of neurons at a similar frequency as in males, despite their sexually distinct vocalizations. These results reveal novel neuromodulators that regulate X. laevis vocal production, and demonstrate the power of constellation pharmacology in identifying the neuronal subtypes marked by functional expression of cell-specific receptors in non-genetic model organisms.

Evolution and Systematics

2002 ◽  
Vol 11 ◽  
pp. 77-96
Author(s):  
Sandra J. Carlson
Keyword(s):  
Biological Process ◽  
Vast Number ◽  
Common Descent ◽  
Living Things ◽  
Geological Past ◽  
Evolutionary Context ◽  
Similarity And Difference ◽  
Life On Earth ◽  
Diversity Of Life

The biological process of evolution—descent with modification—generates and structures the remarkable diversity of life on Earth today and in the geological past. Take a moment to consider the vast number of different kinds of living things: mushrooms, koalas, sunflowers, whales, mosquitoes, kelp, bacteria, tapeworms, lichens, clams, redwoods,…the list could go on and on, seemingly forever. Without some understanding of how the diversity of life was generated, the scope of the diversity may seem overwhelming, perhaps even unknowable. Fortunately the structure of this extraordinary diversity, generated by the process of evolution, can be discovered using the methods of systematics. Evolution can be thought of as “an axiom from which systematic methods and concepts are deduced” (de Queiroz, 1988). Systematics, therefore, provides a way to organize the diversity surrounding us, and make sense of it in an evolutionary framework. Patterns of similarity and difference in morphology, genetics, and development—the evidence of evolution—can only be explained in an evolutionary context by means of systematics. No other method seeks to identify patterns that are evolutionary in origin, generated by the process of common descent.

Integrative Physiology and Functional Genomics of Epithelial Function in a Genetic Model Organism

2003 ◽  
Vol 83 (3) ◽  
pp. 687-729 ◽  
Author(s):  
JULIAN A. T. DOW ◽  
SHIREEN A. DAVIES
Keyword(s):  
Functional Genomics ◽  
Genetic Model ◽  
Model Organism ◽  
Model Organisms ◽  
Integrative Physiology ◽  
Molecular Approaches ◽  
Physiological Analysis ◽  
Organ Level ◽  
And Control ◽  
Reductionist Approach

Dow, Julian A. T, and Shireen A. Davies. Integrative Physiology and Functional Genomics of Epithelial Function in a Genetic Model Organism. Physiol Rev 83: 687–729, 2003; 10.1152/physrev.00035.2002.—Classically, biologists try to understand their complex systems by simplifying them to a level where the problem is tractable, typically moving from whole animal and organ-level biology to the immensely powerful “cellular” and “molecular” approaches. However, the limitations of this reductionist approach are becoming apparent, leading to calls for a new, “integrative” physiology. Rather than use the term as a rallying cry for classical organismal physiology, we have defined it as the study of how gene products integrate into the function of whole tissues and intact organisms. From this viewpoint, the convergence between integrative physiology and functional genomics becomes clear; both seek to understand gene function in an organismal context, and both draw heavily on transgenics and genetics in genetic models to achieve their goal. This convergence between historically divergent fields provides powerful leverage to those physiologists who can phrase their research questions in a particular way. In particular, the use of appropriate genetic model organisms provides a wealth of technologies (of which microarrays and knock-outs are but two) that allow a new precision in physiological analysis. We illustrate this approach with an epithelial model system, the Malpighian (renal) tubule of Drosophila melanogaster. With the use of the beautiful genetic tools and extensive genomic resources characteristic of this genetic model, it has been possible to gain unique insights into the structure, function, and control of epithelia.

scholarly journals Semantic Multi-Classifier Systems Identify Predictive Processes in Heart Failure Models across Species

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 158
Author(s):  
Ludwig Lausser ◽  
Lea Siegle ◽  
Wolfgang Rottbauer ◽  
Derk Frank ◽  
Steffen Just ◽  
...  
Keyword(s):  
Heart Failure ◽  
Regulatory Networks ◽  
Large Scale ◽  
Genetic Model ◽  
Model Organism ◽  
Model Organisms ◽  
Classifier Systems ◽  
Experimental Conditions ◽  
Kegg Pathways ◽  
High Level

Genetic model organisms have the potential of removing blind spots from the underlying gene regulatory networks of human diseases. Allowing analyses under experimental conditions they complement the insights gained from observational data. An inevitable requirement for a successful trans-species transfer is an abstract but precise high-level characterization of experimental findings. In this work, we provide a large-scale analysis of seven weak contractility/heart failure genotypes of the model organism zebrafish which all share a weak contractility phenotype. In supervised classification experiments, we screen for discriminative patterns that distinguish between observable phenotypes (homozygous mutant individuals) as well as wild-type (homozygous wild-types) and carriers (heterozygous individuals). As the method of choice we use semantic multi-classifier systems, a knowledge-based approach which constructs hypotheses from a predefined vocabulary of high-level terms (e.g., Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways or Gene Ontology (GO) terms). Evaluating these models leads to a compact description of the underlying processes and guides the screening for new molecular markers of heart failure. Furthermore, we were able to independently corroborate the identified processes in Wistar rats.

scholarly journals The fruit fly at the interface of diagnosis and pathogenic mechanisms of rare and common human diseases

2019 ◽  
Vol 28 (R2) ◽  
pp. R207-R214 ◽  
Author(s):  
Hugo J Bellen ◽  
Michael F Wangler ◽  
Shinya Yamamoto
Keyword(s):  
Rare Disease ◽  
Gene Function ◽  
Rare Variants ◽  
Genetic Model ◽  
Model Organism ◽  
Model Organisms ◽  
Pathogenic Mechanisms ◽  
Disease Mechanisms ◽  
The Impact ◽  
Undiagnosed Diseases

Abstract Drosophila melanogaster is a unique, powerful genetic model organism for studying a broad range of biological questions. Human studies that probe the genetic causes of rare and undiagnosed diseases using massive-parallel sequencing often require complementary gene function studies to determine if and how rare variants affect gene function. These studies also provide inroads to disease mechanisms and therapeutic targets. In this review we discuss strategies for functional studies of rare human variants in Drosophila. We focus on our experience in establishing a Drosophila core of the Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) and concurrent fly studies with other large genomic rare disease research efforts such as the Centers for Mendelian Genomics. We outline four major strategies that use the latest technology in fly genetics to understand the impact of human variants on gene function. We also mention general concepts in probing disease mechanisms, therapeutics and using rare disease to understand common diseases. Drosophila is and will continue to be a fundamental genetic model to identify new disease-causing variants, pathogenic mechanisms and drugs that will impact medicine.

scholarly journals On the Modeling of the Three Types of Non-spiking Neurons of the Caenorhabditis elegans

2020 ◽  
pp. 2050063
Author(s):  
Loïs Naudin ◽  
Nathalie Corson ◽  
M. A. Aziz-Alaoui ◽  
Juan Luis Jiménez Laredo ◽  
Thibaut Démare
Keyword(s):  
Experimental Data ◽  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Biological Research ◽  
C Elegans ◽  
Living Things ◽  
One Step ◽  
Art Research ◽  
High Degree

The nematode Caenorhabditis elegans (C. elegans) is a well-known model organism in neuroscience. The relative simplicity of its nervous system, made up of few hundred neurons, shares some essential features with more sophisticated nervous systems, including the human one. If we are able to fully characterize the nervous system of this organism, we will be one step closer to understanding the mechanisms underlying the behavior of living things. Following a recently conducted electrophysiological survey on different C. elegans neurons, this paper aims at modeling the three non-spiking RIM, AIY and AFD neurons (arbitrarily named with three upper case letters by convention). To date, they represent the three possible forms of non-spiking neuronal responses of the C. elegans. To achieve this objective, we propose a conductance-based neuron model adapted to the electrophysiological features of each neuron. These features are based on current biological research and a series of in-silico experiments which use differential evolution to fit the model to experimental data. From the obtained results, we formulate a series of biological hypotheses regarding currents involved in the neuron dynamics. These models reproduce experimental data with a high degree of accuracy while being biologically consistent with state-of-the-art research.

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