InterMOD: integrated data and tools for the unification of model organism research

Abstract Model organisms are widely used for understanding basic biology and have significantly contributed to the study of human disease. In recent years, genomic analysis has provided extensive evidence of widespread conservation of gene sequence and function amongst eukaryotes, allowing insights from model organisms to help decipher gene function in a wider range of species. The InterMOD consortium is developing an infrastructure based around the InterMine data warehouse system to integrate genomic and functional data from a number of key model organisms, leading the way to improved cross-species research. So far including budding yeast, nematode worm, fruit fly, zebrafish, rat and mouse, the project has set up data warehouses, synchronized data models and created analysis tools and links between data from different species. The project unites a number of major model organism databases, improving both the consistency and accessibility of comparative research, to the benefit of the wider scientific community.

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Chromatin Structure and Function in Mosquitoes

Frontiers in Genetics ◽

10.3389/fgene.2020.602949 ◽

2020 ◽

Vol 11 ◽

Author(s):

Óscar M. Lezcano ◽

Miriam Sánchez-Polo ◽

José L. Ruiz ◽

Elena Gómez-Díaz

Keyword(s):

Drosophila Melanogaster ◽

Regulatory Networks ◽

Genome Structure ◽

Nuclear Architecture ◽

Model Organism ◽

Fruit Fly ◽

Model Organisms ◽

Epigenetic Mechanisms ◽

West Nile Fever ◽

And Function

The principles and function of chromatin and nuclear architecture have been extensively studied in model organisms, such as Drosophila melanogaster. However, little is known about the role of these epigenetic processes in transcriptional regulation in other insects including mosquitoes, which are major disease vectors and a worldwide threat for human health. Some of these life-threatening diseases are malaria, which is caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes; dengue fever, which is caused by an arbovirus mainly transmitted by Aedes aegypti; and West Nile fever, which is caused by an arbovirus transmitted by Culex spp. In this contribution, we review what is known about chromatin-associated mechanisms and the 3D genome structure in various mosquito vectors, including Anopheles, Aedes, and Culex spp. We also discuss the similarities between epigenetic mechanisms in mosquitoes and the model organism Drosophila melanogaster, and advocate that the field could benefit from the cross-application of state-of-the-art functional genomic technologies that are well-developed in the fruit fly. Uncovering the mosquito regulatory genome can lead to the discovery of unique regulatory networks associated with the parasitic life-style of these insects. It is also critical to understand the molecular interactions between the vectors and the pathogens that they transmit, which could hold the key to major breakthroughs on the fight against mosquito-borne diseases. Finally, it is clear that epigenetic mechanisms controlling mosquito environmental plasticity and evolvability are also of utmost importance, particularly in the current context of globalization and climate change.

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Quantitative investigation reveals distinct phases in Drosophila sleep

Communications Biology ◽

10.1038/s42003-021-01883-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Xiaochan Xu ◽

Wei Yang ◽

Binghui Tian ◽

Xiuwen Sui ◽

Weilai Chi ◽

...

Keyword(s):

Drosophila Melanogaster ◽

General Pattern ◽

Model Organism ◽

Infrared Camera ◽

Fruit Fly ◽

Genetic Dissection ◽

Power Law Distribution ◽

Quantitative Investigation ◽

Waking Up ◽

Set Up

AbstractThe fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

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

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.681593 ◽

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.

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Model and Non-model Insects in Chronobiology

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2020.601676 ◽

2020 ◽

Vol 14 ◽

Author(s):

Katharina Beer ◽

Charlotte Helfrich-Förster

Keyword(s):

Circadian Clock ◽

Genetic Manipulation ◽

Model Organism ◽

Fruit Fly ◽

Sun Compass ◽

Clock Networks ◽

The Social ◽

And Function ◽

Circadian Behavior ◽

Photoperiodic Diapause

The fruit fly Drosophila melanogaster is an established model organism in chronobiology, because genetic manipulation and breeding in the laboratory are easy. The circadian clock neuroanatomy in D. melanogaster is one of the best-known clock networks in insects and basic circadian behavior has been characterized in detail in this insect. Another model in chronobiology is the honey bee Apis mellifera, of which diurnal foraging behavior has been described already in the early twentieth century. A. mellifera hallmarks the research on the interplay between the clock and sociality and complex behaviors like sun compass navigation and time-place-learning. Nevertheless, there are aspects of clock structure and function, like for example the role of the clock in photoperiodism and diapause, which can be only insufficiently investigated in these two models. Unlike high-latitude flies such as Chymomyza costata or D. ezoana, cosmopolitan D. melanogaster flies do not display a photoperiodic diapause. Similarly, A. mellifera bees do not go into “real” diapause, but most solitary bee species exhibit an obligatory diapause. Furthermore, sociality evolved in different Hymenoptera independently, wherefore it might be misleading to study the social clock only in one social insect. Consequently, additional research on non-model insects is required to understand the circadian clock in Diptera and Hymenoptera. In this review, we introduce the two chronobiology model insects D. melanogaster and A. mellifera, compare them with other insects and show their advantages and limitations as general models for insect circadian clocks.

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The Drosophila Larval Locomotor Circuit Provides a Model to Understand Neural Circuit Development and Function

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.684969 ◽

2021 ◽

Vol 15 ◽

Author(s):

Iain Hunter ◽

Bramwell Coulson ◽

Aref Arzan Zarin ◽

Richard A. Baines

Keyword(s):

Neural Circuits ◽

Neural Circuit ◽

Fruit Fly ◽

Model Organisms ◽

Generic Model ◽

Critical Periods ◽

Neuroscience Research ◽

Circuit Development ◽

And Function ◽

Model Circuit

It is difficult to answer important questions in neuroscience, such as: “how do neural circuits generate behaviour?,” because research is limited by the complexity and inaccessibility of the mammalian nervous system. Invertebrate model organisms offer simpler networks that are easier to manipulate. As a result, much of what we know about the development of neural circuits is derived from work in crustaceans, nematode worms and arguably most of all, the fruit fly, Drosophila melanogaster. This review aims to demonstrate the utility of the Drosophila larval locomotor network as a model circuit, to those who do not usually use the fly in their work. This utility is explored first by discussion of the relatively complete connectome associated with one identified interneuron of the locomotor circuit, A27h, and relating it to similar circuits in mammals. Next, it is developed by examining its application to study two important areas of neuroscience research: critical periods of development and interindividual variability in neural circuits. In summary, this article highlights the potential to use the larval locomotor network as a “generic” model circuit, to provide insight into mammalian circuit development and function.

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The Resource Identification Initiative: A cultural shift in publishing

F1000Research ◽

10.12688/f1000research.6555.2 ◽

2015 ◽

Vol 4 ◽

pp. 134 ◽

Cited By ~ 6

Author(s):

Anita Bandrowski ◽

Matthew Brush ◽

Jeffery S. Grethe ◽

Melissa A. Haendel ◽

David N. Kennedy ◽

...

Keyword(s):

Model Organism ◽

Pilot Project ◽

Model Organisms ◽

Dramatic Improvement ◽

Reporting Practices ◽

Resource Identification ◽

Support Of Research ◽

Machine Readable ◽

Model Organism Databases ◽

Research Resources

A central tenet in support of research reproducibility is the ability to uniquely identify research resources, i.e., reagents, tools, and materials that are used to perform experiments. However, current reporting practices for research resources are insufficient to allow humans and algorithms to identify the exact resources that are reported or answer basic questions such as “What other studies used resource X?” To address this issue, the Resource Identification Initiative was launched as a pilot project to improve the reporting standards for research resources in the methods sections of papers and thereby improve identifiability and reproducibility. The pilot engaged over 25 biomedical journal editors from most major publishers, as well as scientists and funding officials. Authors were asked to include Research Resource Identifiers (RRIDs) in their manuscripts prior to publication for three resource types: antibodies, model organisms, and tools (including software and databases). RRIDs represent accession numbers assigned by an authoritative database, e.g., the model organism databases, for each type of resource. To make it easier for authors to obtain RRIDs, resources were aggregated from the appropriate databases and their RRIDs made available in a central web portal (www.scicrunch.org/resources). RRIDs meet three key criteria: they are machine readable, free to generate and access, and are consistent across publishers and journals. The pilot was launched in February of 2014 and over 300 papers have appeared that report RRIDs. The number of journals participating has expanded from the original 25 to more than 40. Here, we present an overview of the pilot project and its outcomes to date. We show that authors are generally accurate in performing the task of identifying resources and supportive of the goals of the project. We also show that identifiability of the resources pre- and post-pilot showed a dramatic improvement for all three resource types, suggesting that the project has had a significant impact on reproducibility relating to research resources.

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Network topology of the marmoset connectome

Network Neuroscience ◽

10.1162/netn_a_00159 ◽

2020 ◽

Vol 4 (4) ◽

pp. 1181-1196

Author(s):

Zhen-Qi Liu ◽

Ying-Qiu Zheng ◽

Bratislav Misic

Keyword(s):

Network Architecture ◽

Model Organism ◽

Common Marmoset ◽

Model Organisms ◽

Neuronal Populations ◽

Behavioral Studies ◽

Small Set ◽

And Function ◽

Organizational Principles ◽

The Brain

The brain is a complex network of interconnected and interacting neuronal populations. Global efforts to understand the emergence of behavior and the effect of perturbations depend on accurate reconstruction of white matter pathways, both in humans and in model organisms. An emerging animal model for next-generation applied neuroscience is the common marmoset ( Callithrix jacchus). A recent open respository of retrograde and anterograde tract tracing presents an opportunity to systematically study the network architecture of the marmoset brain (Marmoset Brain Architecture Project; http://www.marmosetbrain.org ). Here we comprehensively chart the topological organization of the mesoscale marmoset cortico-cortical connectome. The network possesses multiple nonrandom attributes that promote a balance between segregation and integration, including near-minimal path length, multiscale community structure, a connective core, a unique motif composition, and multiple cavities. Altogether, these structural attributes suggest a link between network architecture and function. Our findings are consistent with previous reports across a range of species, scales, and reconstruction technologies, suggesting a small set of organizational principles universal across phylogeny. Collectively, these results provide a foundation for future anatomical, functional, and behavioral studies in this model organism.

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The Alliance of Genome Resources: Building a Modern Data Ecosystem for Model Organism Databases

Genetics ◽

10.1534/genetics.119.302523 ◽

2019 ◽

Vol 213 (4) ◽

pp. 1189-1196 ◽

Cited By ~ 6

Author(s):

Keyword(s):

Laboratory Mouse ◽

Model Organism ◽

Biological Information ◽

Model Organisms ◽

Data Types ◽

Access Methods ◽

Data Archives ◽

Public Data ◽

Data Ecosystem ◽

Model Organism Databases

Model organisms are essential experimental platforms for discovering gene functions, defining protein and genetic networks, uncovering functional consequences of human genome variation, and for modeling human disease. For decades, researchers who use model organisms have relied on Model Organism Databases (MODs) and the Gene Ontology Consortium (GOC) for expertly curated annotations, and for access to integrated genomic and biological information obtained from the scientific literature and public data archives. Through the development and enforcement of data and semantic standards, these genome resources provide rapid access to the collected knowledge of model organisms in human readable and computation-ready formats that would otherwise require countless hours for individual researchers to assemble on their own. Since their inception, the MODs for the predominant biomedical model organisms [Mus sp. (laboratory mouse), Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Danio rerio, and Rattus norvegicus] along with the GOC have operated as a network of independent, highly collaborative genome resources. In 2016, these six MODs and the GOC joined forces as the Alliance of Genome Resources (the Alliance). By implementing shared programmatic access methods and data-specific web pages with a unified “look and feel,” the Alliance is tackling barriers that have limited the ability of researchers to easily compare common data types and annotations across model organisms. To adapt to the rapidly changing landscape for evaluating and funding core data resources, the Alliance is building a modern, extensible, and operationally efficient “knowledge commons” for model organisms using shared, modular infrastructure.

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Functional conservation in genes and pathways linking ageing and immunity

Immunity & Ageing ◽

10.1186/s12979-021-00232-1 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Daniel K. Fabian ◽

Matías Fuentealba ◽

Handan Melike Dönertaş ◽

Linda Partridge ◽

Janet M. Thornton

Keyword(s):

Immune System ◽

Fruit Fly ◽

Model Organisms ◽

Current Evidence ◽

Future Research ◽

Functional Conservation ◽

Human Orthologs ◽

Evolutionarily Conserved ◽

Nematode Worm ◽

Pathogenic Infection

AbstractAt first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the house mouse Mus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.

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