The NeuroDiscovery Center's Laboratory for Drug Discovery in Neurodegeneration (LDDN) was established to discover chemical agents from which we and others will develop a new generation of drugs to treat neurodegenerative diseases. To accomplish this goal, LDDN has recruited a permanent staff of industry-seasoned scientists with expertise in assay development, laboratory automation, informatics, and medicinal chemistry, to work in close collaboration with principal investigators from the academic neuroscience community. In this way, LDDN helps transform discoveries in the basic biology of neurodegeneration into opportunities for drug discovery.
(While priority is given to members investigating neurodegenerative diseases and the central nervous system, we welcome enquiries from all investigators.)
Designing and developing an assay based on the basic science and a hypothesis related to neurodegeneration
We welcome research departments and others involved in the synthesis of "drug-like" molecules to submit compounds to the LDDN for testing in our various assays related to neurodegenerative diseases
Screening is done via a robotic workstation. Assays are assembled on 384 well plates, test compounds are added and the completed assay mixtures are loaded into an automated multimodal plate reader where the readout is quantified. Data, which is collected locally by a PC interfaced to the plate reader, is then downloaded to a Sun server for processing and storage (see below). With our current robot system, we can screen a typical assay against 150,000 compounds in four to six weeks. "Hits" that are discovered in a screen are then confirmed and IC50 values determined. Assay hits that have well-behaved titration curves and IC50 values less than10 µM are then subjected to a series of secondary assays including validation assays, selectivity tests and mechanistic studies. In the selectivity assays, we determine how a given hit behaves in assays of targets that are similar to the primary assay. The goal is typically to focus on the most selective inhibitors. In mechanistic studies, we hope to discover how the compound interacts with its target.
Introduction to the GE In Cell Analyzer 2000 for High Content Analysis (HCA). Drug discovery, automation, medicinal chemistry
Limited training will be available via personnel of the LDDN
The IN Cell Analyzer 2000 is an automated epifluorescence based microscope system for flexible assay development and cellular analysis using a range of dedicated analysis modules. It is a modular platform that can be used in screening, lead profiling, target validation and assay development. The unit is a bench top instrument based on a Nikon microscope, motorized stage, high resolution CCD camera, and fast laser-based confocal auto focus.
Live cells can be observed in culture for responses to potential drug compounds to ascertain whether the compounds will be effective as drugs or toxic to cells, or to delineate gene function. By analyzing real-time events in live cells, the platform provides biologically relevant information, a pre-requisite to understanding functional biology and the role genes and proteins play in the cause of disease.
Examples of some of the more common applications are given below:
• Calcium imaging
• Cell cycle reporting
• Cell differentiation
• Cell migration
• Predictive toxicity
• Live cell imaging
• Micronuclei formation
• Morphology analysis
• Neuronal function
• Neurite outgrowth
• Organelle and protein trafficking studies
• Receptor activation
• RNAi analysis
• Signaling pathway analysis
• Stem cells
• Tissue imaging
Our chemists optimize compounds through a program of medicinal chemistry to increase potency, reduce toxicity and to address physical-chemical and pharmacology properties (i.e. pharmacokinetics).We welcome research departments and others involved in the synthesis of "drug-like" molecules to submit compounds to the LDDN for testing in our various assays related to neurodegenerative diseases
Drug Discovery in Neurodegeneration has not received any reviews.
Drug Discovery in Neurodegeneration has not received any endorsements.