Microfluidic Systems to Study the Biology of Human Diseases and Identify Potential Therapeutic Targets in Caenorhabditis elegans

2017 ◽  
pp. 581-608
Author(s):  
Pouya Rezai ◽  
Sangeena Salam ◽  
P. Ravi Selvaganapathy ◽  
Bhagwati P. Gupta
Keyword(s):  
Caenorhabditis Elegans ◽  
Therapeutic Targets ◽  
Human Diseases ◽  
Microfluidic Systems

scholarly journals Reinforcement Learning to Boost Molecular Docking upon Protein Conformational Ensemble

2021 ◽  
Author(s):  
Bin Chong ◽  
Yingguang Yang ◽  
Zi-Le Wang ◽  
Han Xing ◽  
Zhirong Liu
Keyword(s):  
Molecular Docking ◽  
Reinforcement Learning ◽  
Intrinsically Disordered Proteins ◽  
Therapeutic Targets ◽  
Human Diseases ◽  
Disordered Proteins ◽  
Conformational Ensemble ◽  
Intrinsically Disordered

Intrinsically disordered proteins (IDPs) widely involve in human diseases and are thus attractive therapeutic targets. In practice, however, it is computationally prohibitive to dock large ligand libraries to thousands and...

scholarly journals Application of microRNA Database Mining in Biomarker Discovery and Identification of Therapeutic Targets for Complex Disease

2020 ◽  
Vol 4 (1) ◽  
pp. 5
Author(s):  
Jennifer L. Major ◽  
Rushita A. Bagchi ◽  
Julie Pires da Silva
Keyword(s):  
Complex Disease ◽  
Biomarker Discovery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Human Diseases ◽  
Mirna Expression Data ◽  
Artery Disease ◽  
Underlying Mechanisms

Over the past two decades, it has become increasingly evident that microRNAs (miRNA) play a major role in human diseases such as cancer and cardiovascular diseases. Moreover, their easy detection in circulation has made them a tantalizing target for biomarkers of disease. This surge in interest has led to the accumulation of a vast amount of miRNA expression data, prediction tools, and repositories. We used the Human microRNA Disease Database (HMDD) to discover miRNAs which shared expression patterns in the related diseases of ischemia/reperfusion injury, coronary artery disease, stroke, and obesity as a model to identify miRNA candidates for biomarker and/or therapeutic intervention in complex human diseases. Our analysis identified a single miRNA, hsa-miR-21, which was casually linked to all four pathologies, and numerous others which have been detected in the circulation in more than one of the diseases. Target analysis revealed that hsa-miR-21 can regulate a number of genes related to inflammation and cell growth/death which are major underlying mechanisms of these related diseases. Our study demonstrates a model for researchers to use HMDD in combination with gene analysis tools to identify miRNAs which could serve as biomarkers and/or therapeutic targets of complex human diseases.

Modeling human diseases in Caenorhabditis elegans

2010 ◽  
Vol 5 (12) ◽  
pp. 1261-1276 ◽  
Author(s):  
Maria Markaki ◽  
Nektarios Tavernarakis
Keyword(s):  
Caenorhabditis Elegans ◽  
Human Diseases

scholarly journals LIGHTHOUSE illuminates therapeutics for a variety of diseases including COVID-19

2021 ◽  
Author(s):  
Hideyuki Shimizu ◽  
Manabu Kodama ◽  
Masaki Matsumoto ◽  
Yasuko Orba ◽  
Michihito Sasaki ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
High Throughput Screening ◽  
Structural Information ◽  
Protein Structures ◽  
Therapeutic Targets ◽  
Basic Research ◽  
Human Diseases ◽  
Docking Simulations ◽  
Research Findings ◽  
Therapeutic Compounds

SUMMARYAlthough numerous promising therapeutic targets for human diseases have been discovered, most have not been successfully translated into clinical practice1. A bottleneck in the application of basic research findings to patients is the enormous cost, time, and effort required for high-throughput screening of potential drugs2 for given therapeutic targets. Recent advances in 3D docking simulations have not solved this problem, given that 3D protein structures with sufficient resolution are not always available and that they are computationally expensive to obtain. Here we have developed LIGHTHOUSE, a graph-based deep learning approach for discovery of the hidden principles underlying the association of small-molecule compounds with target proteins, and we present its validation by identifying potential therapeutic compounds for various human diseases. Without any 3D structural information for proteins or chemicals, LIGHTHOUSE estimates protein-compound scores that incorporate known evolutionary relations and available experimental data. It identified novel therapeutics for cancer, lifestyle-related disease, and bacterial infection. Moreover, LIGHTHOUSE predicted ethoxzolamide as a therapeutic for coronavirus disease 2019 (COVID-19), and this agent was indeed effective against alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that are rampant worldwide. Given that ethoxzolamide is already approved for several diseases, it could be rapidly deployed for the treatment of patients with COVID-19. We envision that LIGHTHOUSE will bring about a paradigm shift in translational medicine, providing a bridge from bench side to bedside.

scholarly journals Synthetic Lethal Genetic Interactions That Decrease Somatic Cell Proliferation in Caenorhabditis elegans Identify the Alternative RFCCTF18 as a Candidate Cancer Drug Target

2009 ◽  
Vol 20 (24) ◽  
pp. 5306-5313 ◽  
Author(s):  
Jessica McLellan ◽  
Nigel O'Neil ◽  
Sanja Tarailo ◽  
Jan Stoepel ◽  
Jennifer Bryan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Caenorhabditis Elegans ◽  
Somatic Cell ◽  
Therapeutic Targets ◽  
Genetic Interactions ◽  
Assay System ◽  
Cancer Drug ◽  
Mild Phenotype ◽  
Synthetic Lethal ◽  
C Elegans

Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFCCTF18 complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans . Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.

scholarly journals Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Elizabeth Moreno-Arriola ◽  
Noemí Cárdenas-Rodríguez ◽  
Elvia Coballase-Urrutia ◽  
José Pedraza-Chaverri ◽  
Liliana Carmona-Aparicio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Second Messengers ◽  
Model Organism ◽  
Human Diseases ◽  
C Elegans ◽  
Molecular Bases

Caenorhabditis elegansis a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic levelin vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes.C. elegansdisplays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance ofC. elegansas an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

Sign in / Sign up

Export Citation Format

Share Document