Model organism futures in precision toxicology: tracking the emergence of a research repertoire.

Ageing is defined as the gradual decline of normal physiological functions in a time-dependent manner. Significant progress has been made in characterising the regulatory processes involved in the mechanisms of ageing which would have been hindered without the use of model organisms. Use of alternative model organisms greatly diversifies our understanding of different factors underpinning the ageing process and the potential translation for human application. Unique characteristics make Daphnia an attractive model organism for research into mechanisms underlying ageing, such as transparent body, short generation time, well-characterised methylome, regenerative capabilities and available naturally occurring ecotypes. Most interestingly, genetically identical female and male Daphnia have evolved different average lifespans, providing a unique opportunity for understanding the underlying mechanisms of ageing and regulation of lifespan. Investigating sex differences in longevity could provide insight into principal mechanisms of ageing and lifespan regulation. In this study we provide evidence in support of establishing genetically identical female and male Daphnia as unique and valuable resources for research into mechanisms of ageing and begin to delineate the mechanisms involved in sex differences in lifespan. We identify significant differences between genders in physiological markers such as lifespan, growth rate, heart rate and swimming speed in addition to molecular markers such as lipid peroxidation product accumulation, thiol content decline and age-dependent decline in DNA damage repair efficiency. Overall, our data indicates that investigating sex differences in longevity in the clonal organism Daphnia under controlled laboratory conditions can provide insight into principal mechanisms of ageing and lifespan regulation.

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

During the 1940s and 1950s, in the early days of molecular biology, biologists tackled the enormous problem of explaining how cells work at the molecular level by applying the tried and tested tools of reductionism. They reduced the complexity of the task in two ways: they focused on a few central molecular mechanisms—replication, transcription, protein synthesis and the control of gene activity—and they chose to use the simplest organisms—bacteria and bacteriophages—in which to study these phenomena. Over time and with more knowledge to hand, biological research expanded to the study of more complex systems, which required the increasing use of higher organisms, including Caenorhabditis elegans , Drosophila , Arabidopsis , zebrafish and rodents. These model organisms became the irreplaceable tools of fundamental biological and clinical research, and helped scientists to amass an enormous amount of knowledge. However, several high‐profile clinical trials in which the use of model organisms failed to predict the serious side effects of some drugs, coupled with the prospect of using human stem‐cell lines in trials and the growing sophistication of in silico methods, have all cast doubt on the future use of model organisms. This is the case at least for research into human diseases, which, after all, drives much of the research in molecular biology. > …the fate of E. coli suggests that model organisms can become even more valuable for studying cellular processes once their biology is well understood Animal rights activists have seized on this argument, but show little interest in appreciating the huge contribution that model organisms have made to molecular biology. Indeed, it is not an exaggeration to say that research on animals has taught us nearly all we know about cell biology—be it transcriptional control, RNA quality control or the structure of chromatin. Of course, some organisms have fallen from grace …

Neuronal ceroid lipofuscinoses are a group of fatal progressive neurodegenerative diseases predominantly affecting children. Identification of mutations that cause neuronal ceroid lipofuscinosis, and subsequent functional and pathological studies of the affected genes, underpins efforts to investigate disease mechanisms and identify and test potential therapeutic strategies. These functional studies and pre-clinical trials necessitate the use of model organisms in addition to cell and tissue culture models as they enable the study of protein function within a complex organ such as the brain and the testing of therapies on a whole organism. To this end, a large number of disease models and genetic tools have been identified or created in a variety of model organisms. In this review, we will discuss the ethical issues associated with experiments using model organisms, the factors underlying the choice of model organism, the disease models and genetic tools available, and the contributions of those disease models and tools to neuronal ceroid lipofuscinosis research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

Model organisms are a living form of scientific models. Despite the widespread use of model organisms in scientific research, the actual representational relationship between model organisms and their target species is often poorly characterized in the context of cross-species research. Many model organisms do not represent the target species adequately, let alone accurately. This is partly due to the complex and emergent life phenomena in the organism, and partly due to the fact that a model organism is always taken to represent a broad range of diverse organisms. More often than not, model organisms are taken as a reference point for an extrapolation to be made to the unknown characteristics of other species. I propose to view model organisms as analogue simulators which represent the emergent phenomenon in the context of cross-species research. A model organism represents a wide range of species by simulating their molecular microstates which underlie various emergent phenomena. I show that although model organisms represent the target species inadequately at many levels of complexity, they have epistemic values as a simulator in virtue of which the emergent phenomenon can be modeled dynamically, a virtue that is hardly attainable by non-dynamic models.

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 complexity of food organism interactions necessitates the use of model organisms to understand physiological and pathological processes. In nutrition research, model organisms were initially used to understand how macro and micronutrients are handled in the organism. Currently, in nutritional systems biology, models of increasing complexity are needed in order to determine the global organisation of a biological system and the interaction with food and food components. Originally driven by genetics, certain model organisms have become most prominent. Model organisms are more accessible systems than human beings and include bacteria, yeast, flies, worms, and mammals such as mice. Here, the origin and the reasons to become the most prominent models are presented. Moreover, their applicability in molecular nutrition research is illustrated with selected examples.

Model organisms are important tools in modern biology and have been used elucidate mechanism underlying processes, such as development, heredity, neuronal signaling, and phototropism, to name but a few. In this context, the use of model organisms is predicated on uncovering evolutionarily conserved features of biological processes in the expectation that the findings will be applicable to organisms that are either inaccessible or intractable for direct experimentation. For the most part, particular species have been adapted as model organisms because they can be easily reared and manipulated in the laboratory. In contrast, a major goal in the field of evolutionary developmental biology (Evo-Devo) is to identify and elucidate the differences in developmental processes among species associated with the dramatic range of body plans among organisms, and how these differences have emerged over time in various branches of phylogeny. At first glance then, it would appear that the concept of model organisms for Evo-Devo is oxymoronic. In fact, however, laboratory-compatible, experimentally tractable species are of great use for Evo-Devo, subject to the condition that the ensemble of models investigated should reflect the range of taxonomic diversity, and for this purpose glossiphoniid leeches are useful. Four decades ago (1975), leeches of the species-rich genus Helobdella (Lophotrochozoa; Annelida; Clitellata; Hirudinida; Glossiphoniidae) were collected in Stow Lake, Golden Gate Park, San Francisco, CA (USA). These and other Helobdella species may be taken as Evo-Devo models of leeches, clitellate annelids, and the super-phylum Lophotrochozoa. Here we depict/discuss the biology/taxonomy of these Evo-Devo systems, and the challenges of identifying species within Helobdella. In addition, we document that H. austinensis has been established as a new model organism that can easily be cultivated in the laboratory. Finally, we provide an updated scheme illustrating the unique germ line/soma-differentiation during early development and speculate on the mechanisms of sympatric speciation in this group of aquatic annelids.

방사선 생물학에서 방사선에 대한 반응으로 매개되는 다양한 기작에 대한 분석을 위해 여러 종류의 모델 생물체를 사용해 왔다. 모델 생물체는 생물학적으로 온전한 in vivo 환경을 제공할 수 있기 때문에 방사선에 의해 발생되는 세포 내 현상은 물론 생리적인 현상이나 병리학적인 현상을 규명하는 데 있어서 모델 생물체를 사용하는 것은 효과적인 방법이 될 수 있다. 지금까지 축적된, 모델 생물체를 이용한 방사선 생물학적 연구결과들은 새로운 방사선치료 보조제의 개발, 방사선치료 효율 증진 등에 적용되어 여러 질병에 대한 임상연구의 기초가 되어왔다. 이렇게 유용하게 사용된 여러 모델 생물체에 있어서, 각각의 모델에 대한 개별적인 정보에 대한 연구는 다양한 방면에서 이루어지고 있지만, 통합적인 비교, 분석 및 정리를 한 경우는 부족한 실정이다. 따라서, 본 논문에서는 방사선 생물학에서 지금까지 많이 사용된 모델 생물체 4종(효모, 예쁜꼬마선충, 초파리, 생쥐)에 대해 각 생물체가 갖는 모델로써의 특징과 장단점 그리고 방사선 생물학 연구에 이용된 사례 등을 서술하고자 한다. In radiation biology, analysis of various mechanisms in response to radiation has been accomplished with the use of model organisms. These model organisms are powerful tools for providing a biologically intact in vivo environment to assess physiological and pathophysiological processes affected by radiation. Accumulated data using these models have been applied to human clinical studies (including the evaluation of radiotherapeutic efficacy) and discovery of radiotherapy reagents. However, there are few studies to provide overall integrated information about these useful model organisms. Thus, this review summarizes the results of radiation biology studies using four well-known model organisms: yeast, Caenorhabditis elegans, Drosophila melanogaster, and mice.

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.

Genetics and pharmacology of longevity: the road to therapeutics for healthy aging.

Model organisms are an important tool for the development and validation of analytical approaches for proteomics and for the study of basic mechanisms of biological processes. The Initiative on Model Organism Proteomics (iMOP) organized a session during the 11th HUPO World Congress in Boston in 2012, highlighting the potential of proteomics studies in model organism for the elucidation of important mechanisms regulating the interaction of humans with its environment. Major subjects were the use of model organisms for the study of molecular events triggering the interaction of host organisms with the surrounding microbiota and the elucidation of the complex influence of nutrition on the health of human beings.

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.

Human development and disease are challenging to study because of lack of experimental accessibility to in vivo systems and the complex nature of biological processes. For these reasons researchers turn to the use of model systems, ranging in complexity and scale from single cells to model organisms. While the use of model organisms is valuable for studying physiology and pathophysiology in an in vivo context and for aiding pre-clinical development of therapeutics, animal models are costly, difficult to interrogate, and not always equivalent to human biology. For these reasons, three-dimensional (3D) cell cultures have emerged as an attractive model system that contains key aspects of in vivo tissue and organ complexity while being more experimentally tractable than model organisms. In particular, organ-on-a-chip and organoid models represent orthogonal approaches that have been able to recapitulate characteristics of physiology and disease. Here, we review advances in these two categories of 3D cultures and applications in studying development and disease. Additionally, we discuss development of key technologies that facilitate the generation of 3D cultures, including microfluidics, biomaterials, genome editing, and imaging technologies.

The past 20 years of ecology and evolution