Short Course Descriptions
Sunday, April 11, 2010
Automated Assays for Drug Discovery: A Toolbox Approach to Selecting an Appropriate Assay
This course will focus on one central question: given a multitude of assay technologies available for a given target, how does one go about selecting an appropriate technology? What criteria should one examine during this process? We will describe a toolbox approach: a generic, flexible set of assay methodologies and show how they can be applied to some of the major target classes in molecular and cell-based screening. Assay case studies will be presented, and course participants will engage in discussions of toolbox formats comparing the robustness of different assays as well as cost and user-friendliness.
Level: all levels
BacMam101: Practical Aspects of Making and Using BacMam Vectors
BacMam engineered recombinant baculovirus vectors can efficiently deliver expression cassettes to a wide variety of mammalian cell types. The ease of generation, the safety and the unparalleled experimental versatility of BacMam vectors makes transient gene delivery in support of cell-based assays a viable option for high-throughput screening. This course will cover basic practical aspects of vector generation and provide detailed instruction on how to optimally utilize BacMam vectors for development and support of cell-based assays. There will be plenty of time available during the class for discussion as well as Q&A. The course will describe the basic principles of viral generation, insect cell culture and recombinant baculovirus growth procedures as well as providing details of how to develop BacMam-based assays.
Level: Current users of the technology as well as those wishing to learn how they might implement BacMam technology in their own laboratory.
Establishing Cell-Based Assays for Screening
Cell-based assays are essential tools in the drug discovery industry. They are important in high-throughput screening as well as target identification and secondary compound profiling. Selecting the most appropriate assay from the large number available and establishing that assay within a minimal time frame are critical to a project's success. This course will begin with an overview of critical factors to consider for selection, maintenance, and characterization of cells necessary to develop successful cell-based assays for HTS. Specific application examples covered by individual instructors will include: 1) an overview of cell viability, cytotoxicity, and apoptosis assays including multiplexing with genetic reporters; 2) the scale-up and use of frozen cells for GPCR assays such as cAMP, cellular reporters, calcium mobilization or label-free electrical impedance measurements; and 3) an overview of the application and use of RNAi technology for screening.
Level: all levels
High content screening (HCS) is a powerful technology platform for implementing functional cell-based assays that allow truly multiparametric analysis in the physiological context of intact cells. This course will provide a state of the art overview of the components of HCS (instrumentation, fluorescent labels, HC assay development, automated image analysis, and multi-parametric data analysis) together with some showcases of small molecule and RNAi high-content screens in industry and academia.
Level: Both beginners as well as experienced persons wishing to be refreshed on some aspects and more recent developments would greatly benefit. The course is directed towards attendees both from industry and from academia.
In Vitro ADME Screening: Basic Concepts and Practical Methods
This course will cover principals and methods of in vitro ADME testing. Selected topics include solubility, plasma protein binding, absorption including Caco-2, metabolic stability, cytochrome P450 inhibition and induction. Attendees of this course will gain an understanding of basic concepts and methods for in vitro ADME (Absorption, Distribution, Metabolism and Excretion) testing. In addition, attendees will learn how to interpret test findings, with the aim of selecting small molecule drug candidates with favorable pharmacokinetic properties. The merits of selected common and more recent approaches will be examined.
Level: Individuals with little or no exposure to ADME concepts would benefit from this course. More experienced individuals seeking “refresher” training or exposure to alternate views will also benefit. Expected participants would include synthetic chemists, nonclinical and clinical scientists, individuals from regulatory agencies and project team leaders.
Biophysical / label-free methods are becoming an important tool in lead finding and drug discovery complementing, but not replacing, more classical assay technologies. A collection of long-standing, "gold-standard" label-free methods are rapidly being augmented by novel, higher throughput techniques, presenting both an extensive but also confusing landscape of biophysics tools in drug discovery. A key question is how to enable efficient and more systematic use of the biophysics portfolio in early drug discovery programs. Ultimately they are expected to offer not only novel ways of hit finding, but also more efficient ways to identify and advance true hits for chemistry and later stage biology. This short course will focus on biophysics technologies with highest impact and applicability for screening and lead finding (e.g. Protein Thermal Denaturation and Aggregation [DSF aka Thermofluor, DSLS aka Stargazer, Atlas]; SPR, Interferometry and Waveguide Grating [e.g. SPR aka Biacore, Corning Epic, SRU BIND, Fortebio]; NMR; Calorimetry (DSC, ITC); Affinity Mass Spectrometry; Dynamic Light scattering. The technologies covered will mainly concern those suitable for “biochemical” applications, cellular assay will only be touched very briefly if technologies can serve both, biochemical and cellular assays.
Level: People interested in getting an overview about the current broad biophysics/label-free portfolio in lead finding, but certainly all persons involved in the field that want to learn about concepts and applications of their "best practice". This course is directed towards attendees from both industry and academia. However due to the vast variety of potential label-free methods and applications, the focus will be drawn on higher throughput technologies suitable in a typical screening / lead finding environment of early drug discovery.
Statistical Methods for In Vitro Assays in Drug Discovery
The course will cover a set of statistical methods that are useful for designing, optimizing, validating, and analyzing in vitro biological assays for use in drug-discovery research. Covered topics will include Z’factor, false positive/ negative rates, dose-response curve fitting, minimum significant ratio, control charting, correlation, and statistical experimental design.
Level: All levels, but some experience with basic statistics (mean, standard deviation, p-value) and some experience with biological assays will be assumed.