scholarly journals Xenopus: An Undervalued Model Organism to Study and Model Human Genetic Disease

2018 ◽  
Vol 205 (5-6) ◽  
pp. 303-313 ◽  
Author(s):  
Martin Blum ◽  
Tim Ott
Keyword(s):  
High Speed ◽  
Molecular Mechanisms ◽  
Genetic Diseases ◽  
Model Organism ◽  
Model Organisms ◽  
Human Genetic Disease ◽  
The Past ◽  
Large Numbers ◽  
Pros And Cons ◽  
Cost Efficient

The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by human geneticists and the biomedical community at large, will be best studied in relevant and predictive model organisms that allow high-speed verification, analysis of underlying developmental, cellular and molecular mechanisms, and establishment of disease models to test therapeutic options. We describe and discuss the pros and cons of the frog Xenopus, which has been extensively used to uncover developmental mechanisms in the past, but which is being underutilized as a biomedical model. We argue that Xenopus complements the more commonly used mouse and zebrafish as a time- and cost-efficient animal model to study human disease alleles and mechanisms.

scholarly journals Transgenic Epigenetics: Using Transgenic Organisms to Examine Epigenetic Phenomena

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Lori A. McEachern
Keyword(s):  
Molecular Mechanisms ◽  
Model Organism ◽  
Evolutionary Conservation ◽  
Model Organisms ◽  
Valuable Insight ◽  
Epigenetic Control ◽  
Transgenic Organisms ◽  
Epigenetic Analysis ◽  
Insight Into ◽  
Epigenetic Processes

Non-model organisms are generally more difficult and/or time consuming to work with than model organisms. In addition, epigenetic analysis of model organisms is facilitated by well-established protocols, and commercially-available reagents and kits that may not be available for, or previously tested on, non-model organisms. Given the evolutionary conservation and widespread nature of many epigenetic mechanisms, a powerful method to analyze epigenetic phenomena from non-model organisms would be to use transgenic model organisms containing an epigenetic region of interest from the non-model. Interestingly, while transgenic Drosophila and mice have provided significant insight into the molecular mechanisms and evolutionary conservation of the epigenetic processes that target epigenetic control regions in other model organisms, this method has so far been under-exploited for non-model organism epigenetic analysis. This paper details several experiments that have examined the epigenetic processes of genomic imprinting and paramutation, by transferring an epigenetic control region from one model organism to another. These cross-species experiments demonstrate that valuable insight into both the molecular mechanisms and evolutionary conservation of epigenetic processes may be obtained via transgenic experiments, which can then be used to guide further investigations and experiments in the species of interest.

scholarly journals How Not To Be in the Wrong Place at the Wrong Time: An Education Primer for Use with “Deposition of Centromeric Histone H3 Variant CENP-A/Cse4 into Chromatin Is Facilitated by Its C-Terminal Sumoylation”

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 333-342
Author(s):  
Yee Mon Thu
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Diseases ◽  
Histone H3 ◽  
Model Organism ◽  
Post Translational Modification ◽  
Genetic Changes ◽  
Equal Distribution ◽  
Link Type ◽  
Histone H3 Variant ◽  
Big Picture

Recent work by Kentaro Ohkuni and colleagues exemplifies how a series of molecular mechanisms contribute to a cellular outcome—equal distribution of chromosomes. Failure to maintain structural and numerical integrity of chromosomes is one contributing factor in genetic diseases such as cancer. Specifically, the authors investigated molecular events surrounding centromeric histone H3 variant Cse4 deposition—a process important for chromosome segregation, using Saccharomyces cerevisiae as a model organism. This study illustrates an example of a post-translational modification—sumoylation—regulating a cellular process and the concept of genetic interactions (e.g., synthetic dosage lethality). Furthermore, the study highlights the importance of using diverse experimental approaches in answering a few key research questions. The authors used molecular biology techniques (e.g., qPCR), biochemical experiments (e.g., Ni-NTA/8His protein purification), as well as genetic approaches to understand the regulation of Cse4. At a big-picture level, the study reveals how genetic changes can lead to subsequent molecular and cellular changes.

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 proteomics database for CNS proteins of the great pond snail Lymnaea stagnalis

2021 ◽  
Author(s):  
Sarah Wooller ◽  
Aikaterini Anagnostopoulou ◽  
Benno Kuropka ◽  
Michael Crossley ◽  
Paul R. Benjamin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Lymnaea Stagnalis ◽  
Model Organism ◽  
Research Area ◽  
Biological Data ◽  
Model Organisms ◽  
Pond Snail ◽  
Data Sets ◽  
Area Of Interest ◽  
Age Related

Applications of key technologies in bioscientific and biomedical research, such as qRT-PCR or LC-MS based proteomics, are generating large biological data sets (omics data) which are useful for the identification and quantification of biomarkers involved in molecular mechanisms of any research area of interest. Genome, transcriptome and proteome databases are already available for a number of model organisms including vertebrates and invertebrates. However, there is insufficient information available for protein sequences of certain invertebrates, such as the great pond snail Lymnaea stagnalis, a model organism that has been used highly successfully in elucidating evolutionarily conserved mechanisms of learning and memory, ageing and age-related as well as amyloid beta induced memory decline. Here, we present the design and benchmarking of a new proteomics database (LymSt-PDB) for the identification of proteins from the Central Nervous System (CNS) of Lymnaea stagnalis by LC-MS based proteomics.

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 Recent Developments in Using Drosophila as a Model for Human Genetic Disease

2018 ◽  
Author(s):  
Christine Oriel ◽  
Paul Lasko
Keyword(s):  
Genetic Disease ◽  
Genetic Variant ◽  
Genetic Diseases ◽  
Model Organisms ◽  
Human Genetic Disease ◽  
New Approach ◽  
Linked Gene ◽  
The Us ◽  
Recent Developments ◽  
Disease Loci

Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach.

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 Recent Developments in Using Drosophila as a Model for Human Genetic Disease

2018 ◽  
Vol 19 (7) ◽  
pp. 2041 ◽  
Author(s):  
Christine Oriel ◽  
Paul Lasko
Keyword(s):  
Genetic Disease ◽  
Genetic Variant ◽  
Genetic Diseases ◽  
Model Organisms ◽  
Human Genetic Disease ◽  
New Approach ◽  
Linked Gene ◽  
The Us ◽  
Recent Developments ◽  
Disease Loci

Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach.

scholarly journals The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids

2021 ◽  
Vol 8 ◽  
Author(s):  
Kseniia Sarieva ◽  
Simone Mayer
Keyword(s):  
Brain Development ◽  
Molecular Mechanisms ◽  
Time Windows ◽  
Fetal Brain ◽  
Model Organisms ◽  
The Past ◽  
Nicotine Consumption ◽  
Simplex Virus ◽  
The Impact

Over the past decades, a growing body of evidence has demonstrated the impact of prenatal environmental adversity on the development of the human embryonic and fetal brain. Prenatal environmental adversity includes infectious agents, medication, and substances of use as well as inherently maternal factors, such as diabetes and stress. These adversities may cause long-lasting effects if occurring in sensitive time windows and, therefore, have high clinical relevance. However, our knowledge of their influence on specific cellular and molecular processes of in utero brain development remains scarce. This gap of knowledge can be partially explained by the restricted experimental access to the human embryonic and fetal brain and limited recapitulation of human-specific neurodevelopmental events in model organisms. In the past years, novel 3D human stem cell-based in vitro modeling systems, so-called brain organoids, have proven their applicability for modeling early events of human brain development in health and disease. Since their emergence, brain organoids have been successfully employed to study molecular mechanisms of Zika and Herpes simplex virus-associated microcephaly, as well as more subtle events happening upon maternal alcohol and nicotine consumption. These studies converge on pathological mechanisms targeting neural stem cells. In this review, we discuss how brain organoids have recently revealed commonalities and differences in the effects of environmental adversities on human neurogenesis. We highlight both the breakthroughs in understanding the molecular consequences of environmental exposures achieved using organoids as well as the on-going challenges in the field related to variability in protocols and a lack of benchmarking, which make cross-study comparisons difficult.

scholarly journals PTEN Gene: A Model for Genetic Diseases in Dermatology

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Corrado Romano ◽  
Carmelo Schepis
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Genetic Diseases ◽  
Pten Gene ◽  
The Past ◽  
Front Office ◽  
Near Future

PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN.

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