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High-throughput Phenotypic Screen Services
Overview of Phenotypic Screen
Successful drug discovery from a phenotypic screening is not necessarily impeded by a lack of molecular insight. Phenotypic screening is usually more physiologically relevant and embraces the ability to study pleiotropic effects. This can be, as clinical practice demonstrates, applied to the discovery of new drugs especially against illnesses where our understanding of the underlying mechanisms is low, such as in the case of common psychosomatic conditions or neurological diseases.
Principle of Phenotypic Screen
Modern phenotypic assays should capture key aspects of the physiological process such as relevant cell types, cell-cell interactions, growth factors, signal transduction pathways, and molecular targets while utilizing in vitro systems amenable to rigorous statistical validation and high throughput operations. An appropriate cellular screening model is chosen according to the type of screening library and the phenotype of interest. Screening libraries can be divided into three classes: small molecule compound libraries, knockdown or deletion libraries, or overexpression libraries. Knockdown or deletion libraries contain either siRNA, shRNA, or gRNA for CRISPR screens. For CRISPR screens, the chosen cell type requires the expression of Cas9 endonuclease. Cells can also express a disease gene that causes the phenotype of interest (e.g., overexpression of tau, α-synuclein, or Htt fragments) and/or a reporter gene (e.g., GFP-labelled LC3 to visualize autophagic flux, a minigene to assess splicing, a luciferase-labeled transgene to visualize up-or downregulation of protein levels).
Fig.1 Schematic of phenotypic screening approaches.1
Phenotypic Screen in CNS Diseases
Phenotypic screens in neurodegeneration are being facilitated by advances in screening models all the way from primitive organisms such as yeast to complex 3D cell models. The outcome of a screen is critically dependent on the design of the assay, the nature of the screening collection, the concentrations of the test molecules, and an appropriate triage effort to confirm the hits. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and frontotemporal dementia (FTD) are debilitating disorders, and there are currently no disease-modifying therapies available to patients. Many of these diseases share common mechanisms and phenotypes (e.g., aberrant protein aggregation, impaired autophagic flux, excitotoxicity, mitochondrial dysfunction). Phenotypic screens are being used to interrogate these and other disease mechanisms in a variety of model systems. Recent examples in ALS, Huntington's disease, Parkinson's disease, and Alzheimer's disease illustrate that a diverse range of techniques can be used to identify hits and lead chemical series that mitigate neurodegeneration-associated phenotypes.
Fig.2 Overview of cell models used in phenotypic screening for neurodegeneration.1
With years of experience focusing on neuroscience, Creative Biolabs has gradually optimized our technology platform with advanced facilities and professional specialists. We are now capable of providing a variety of basic neuroscience assay services, including high-throughput phenotypic screen services. The strong foundations, professional expertise, and Ph.D. level scientists consist of the powerful guarantee of the quality of our services. If you are looking for high-throughput phenotypic screen services or you have any other requirements, please don't hesitate to contact us for more information.
Services at Creative Biolabs
Our company offers high-throughput phenotypic screening services specifically designed for neuroscience research. Our services utilize advanced technology and expertise to screen large libraries of compounds or biological molecules in order to identify potential drug candidates or targets for neurological conditions.
Our services include:
- Assay Development - Our team of scientists will work closely with clients to develop customized assays based on specific phenotypic endpoints relevant to their neuroscience research goals. We have expertise in various assay formats, including imaging-based assays, electrophysiology, and biochemical assays.
- Compound Library Screening - We have access to a diverse library of compounds that can be screened using high-throughput automated platforms. Screening large libraries allows for the identification of novel compounds with potential therapeutic effects.
- Data Analysis and Interpretation - Our bioinformatics team will analyze the high-throughput screening data using advanced algorithms and statistical methods to identify hits and prioritize compounds for further testing.
Our state-of-the-art facilities, experienced scientific team, and cutting-edge technology make us a leading partner for advancing neuroscience research through high-throughput phenotypic screening. We also offer flexibility in our services, including but not limited to:
| Services | Descriptions |
|---|---|
| Primary Cell Lines | We offer the development of neuroscience-based primary cell lines and related customized products. |
| Custom CNS Disease Modeling | Our platform can offer reliable custom CNS disease modeling services including but not limited to Alzheimer's disease models, Huntington's disease models, and Parkinson's disease models. |
| STEMOD™ Advanced Drug Discovery | Our platform has advanced neuroscience ex vivo models, neuroscience assay techniques, and neuroscience research tools. These technologies will cover every important stage of CNS drug discovery, resulting in a one-stop shop for our customers. |
Published Data
Therapeutic discovery for neuropsychiatric disorders would benefit from screening assays that can measure complex phenotypic changes associated with disease mechanisms. However, traditional assays that track complex neuronal phenotypes are poorly scalable and incompatible with high-throughput screening (HTS) programs.
Timothy P. Spicer, et al. created a neuronal phenotype assay platform focused on improving the scalability and affordability of neuronal-based assays capable of tracking disease-related phenotypes. To improve the scalability of neuron-based phenotypic screening assays, they combined genomic targeting of fluorescence-detected reporter genes in rodents with the implementation of low-cost automation and high-density neuronal culture. They developed a set of phenotypic assays that are based on culturing primary neurons from transgenic mice expressing HTS-compatible reporter genes that capture disease-related phenotypes.
Fig. 3 Low- and high-throughput screening against a live primary neuron-based synaptogenesis assay.2
Applications
Our services offer a wide range of applications for neuroscience research. These services enable biotechnology companies to rapidly and efficiently screen large libraries of compounds for their effects on various cellular and physiological phenotypes relevant to neurodegenerative diseases, psychiatric disorders, and other neurological conditions.
- Drug discovery for neurodegenerative diseases
- Target identification for psychiatric disorders
- Functional genomics studies
- Mechanistic studies of neural pathways
Our services provide a powerful tool for biotechnology companies engaged in neuroscience research, allowing them to efficiently and comprehensively explore the effects of compounds on a wide range of cellular and physiological phenotypes relevant to neurological conditions. Through these services, valuable insights can be gained that can drive drug discovery efforts and advance our understanding of the underlying mechanisms of neurodegenerative diseases, psychiatric disorders, and other neurological conditions.
FAQs
Q: What specific assays and technologies do you employ in your high-throughput phenotypic screens for neuroscience research?
A: Our service utilizes advanced imaging technologies coupled with automated image analysis algorithms to screen for various neuronal phenotypes. We employ assays tailored to detect changes in morphology, protein expression, and functional activity of neurons in response to stimuli or treatments. These include neuron calcium imaging, neurite outgrowth assays, and fluorescence-based assays for neurotransmitter release.
Q: What are the scalability options if our neuroscience research project requires increasing the scope or volume of phenotypic screening?
A: Our platform is scalable to accommodate varying project needs. Whether you need to scale up the number of samples screened or integrate additional assays and endpoints, we can tailor our services to meet your evolving research demands. Our flexible approach ensures that we can effectively support projects of different scales and complexities.
Q: Can your phenotypic screen handle high-throughput screening of large compound libraries for drug discovery purposes?
A: Yes, our platform is optimized for high-throughput screening of large compound libraries. We utilize automated systems and advanced robotics to enhance throughput while maintaining assay sensitivity and accuracy. This capability makes our service ideal for accelerating drug discovery efforts targeting neurological disorders and conditions.
Q: What types of neurological models or cell types can be accommodated in your phenotypic screening services?
A: We support a wide range of neurological models and cell types, including primary neurons, induced pluripotent stem cell-derived neurons, and various neuronal cell lines. Our expertise allows us to adapt assays to different model systems, ensuring that your specific research questions can be effectively addressed using our phenotypic screening platform.
Scientific Resources
References
- Brown, D. G. and Wobst, H. J. Opportunities and Challenges in Phenotypic Screening for Neurodegenerative Disease Research. J Med Chem. 2020, 63(5): 1823-1840.
- Spicer, Timothy P., et al. "Improved scalability of neuron-based phenotypic screening assays for therapeutic discovery in neuropsychiatric disorders." Molecular Neuropsychiatry 3.3 (2018): 141-150.
For Research Use Only. Not For Clinical Use.