Short Courses

Sunday, April 6, 2008
8:30am – 5:00pm

Automated Assays for Drug Discovery: A Toolbox Approach to Selecting an Appropriate Assay Technology

Instructors
E. Michael August, Ph.D., Boehringer Ingelheim Pharmaceuticals, Inc. 
Mohammed A. Kashem, Ph.D., Boehringer Ingelheim Pharmaceuticals, Inc.
Hans-Dieter Schubert, Boehringer Ingelheim Pharma GmbH

Course Summary
The 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, reviewing the common and not-so-common approaches to assaying several of the major target classes in molecular and cell-based screening. Course participants will engage in discussions of detection methodologies, comparing the robustness of different assays as well as cost and user-friendliness.

Course Objectives
This course will review various state-of-the art assay and detection technologies available for development and implementation of molecular and cell-based assays for accelerated drug discovery. Specifically, it will provide theoretical background, best practices for the design, development and implementation of automated assays for kinases, proteases, protein-protein interactions, receptor-ligand binding, and other target classes of interest.

Who Would Benefit
Individuals involved in assay development at any level

Course Level
All levels

Establishing Cell-Based Assays for Drug Discovery

Instructors
Lisa Minor, Ph.D., J&J PRD
Eric Johnson, Ph.D., Merck & Co., Inc.
Terry Riss, Ph.D., Promega
Namjin Chung, Bristol-Myers Squibb Company

Course Summary
Cell-based assays are a mainstay of the drug-discovery industry; they are important in both high-throughput screening as well as target identification and secondary compound profiling. Picking the appropriate assay for one's needs from the large number available and establishing that assay within a minimal time frame are critical to a project's success. Using a tag-team approach, this course will teach the student both cell biology critical to assay success, as well as multiple cell-based assay applications. This includes teaching basic cell maintenance and handling, the use of frozen cells for screening, different assay formats for GPCR's such as cAMP, cellular reporters, calcium mobilization or label-free tools such as electrical impedance, the application and use of RNAi technology, as well as the different assay tools for measuring cell viability, cytotoxicity and apoptosis.

Course Objectives
Teach the student the basic strategy and methodology for conducting cell-based assays. Provide a toolbox for picking assays appropriate for a particular need based on evaluations of the advantages and disadvantages of each method.

Who Would Benefit
Both cell culture beginners as well as experienced persons wishing to be refreshed on some basics while being presented with the plethora of assays for each indication.

Course Level
All levels

Imaging and Automated Microscopy for Cell-Based Assays in Drug Discovery:  High-Content Screening (HCS)

Instructors
Ralph Garippa, Ph.D., Roche
Neal Gliksman, Ph.D., MDC
Robert F. Murphy, Ph.D., Carnegie Mellon University

Course Summary
Image-based assays are playing a growing role in the drug discovery environment, enabling functional screening of disease models, biomarker discovery, and toxicology assessments. However, the implementation and use of image-based assays can be more complicated than traditional assay formats. The course will be presented in five parts: (1) Introduction and overview, covering the basic types of cell-based assays that are suited to image-based analysis; (2) Fundamentals of image analysis, from basic feature extraction to algorithm development to trainable classifiers and machine learning; (3) Assembling the information-handling infrastructure; (4) Review of current commercially available instrumentation; and (5) Case studies of development, statistical validation and screening performance metrics.  This course will provide training in both the fundamental principles of digital image analysis and the state-of-the-art of HCS systems, while discussing the practical aspects of developing and utilizing these capabilities.

Course Objectives
(1) Teach the basics of automated image analysis as related to fluorescent cell-based microscopy  (2) Convey, in an unbiased manner, the state-of-the-art in HCS with respect to instrumentation (3) Offer several different solutions, figuring cost and capacity, for image-based data storage and image import/export (4) Examine the components of algorithm design, machine learning tools, object and feature-based characteristics of images  (5) Review actual case studies involving the successful implementation of HCS (in Pharma, Biotech and Academia), citing specific biological applications and highlighting those instances where HCS was enabling (beyond other alternative technologies)

Who Would Benefit
Anyone interested in using automation and robotics for increasing throughput in microscopy-based or laser-line scanning based cellular assays.

Course Level
All levels

In Vitro ADME Screening: Basic Concepts and Practical Methods

Instructors
Vaughn Miller, Ph.D., BD Biosciences
Guangqing Xiao, Ph.D., BD Biosciences
Paul V. Kaplita, Ph.D., Boehringer Ingelheim Pharmaceuticals, Inc.
Ethan Hoffmann, AstraZeneca

Course Summary
This course will provide an overview of the theory and assays of in vitro ADME screening for drug-like properties in drug discovery and development. The following topics will be reviewed: solubility and other physical property assays, permeability & transport, metabolic stability, P450 inhibition & induction, and reactive metabolites.

Course Objectives
This course in meant to be a comprehensive introduction to in vitro ADME. The theory and basic concepts of in vitro ADME screening to support drug discovery and development will be reviewed. Particular attention will be paid to discussing the best practice methods for these assays and data interpretation.

Who Would Benefit
This course is intended for anyone who does not have a strong knowledge of in vitro ADME and seeks to learn the basic concepts to support their responsibilities or interest in drug discovery. Drug discovery scientists and managers from pharmaceutical companies, CROs, and academia may benefit from this course.

Course Level
Beginner and Intermediate

The Pharmaceutical Scientist’s Guide to Solution Kinetic Models: Mathematical Description and Applications

Course Instructor
Gary W. Caldwell, Ph.D., Johnson & Johnson

Course Summary
Solution kinetic models are extremely important concepts for scientists to understand since the process used by pharmaceutical companies to discover and develop marketable drugs is highly dependent upon these models. Unfortunately, in most textbooks the mathematical descriptions necessary to develop a deeper understanding of solution kinetic models are omitted. This is primarily done so that the underlying chemistry and biochemistry principles are not obscured by the “mathematical maze” that is generated from these models. Thus, the objective of this course is to build a solid mathematical foundation of enzyme kinetic models by systematically evolving simple uni- and bi-molecular solution kinetic models to complex enzyme models. In doing so, we will discover that the mathematical maze disappears. Drug-discovery examples (chemical and enzymatic stability, drug transport, pharmacokinetic models, saturation binding,  competitive saturation binding, etc.) will be presented to demonstrate how solution kinetic models are used to select drug candidates.

Course Objectives
After the course, you will be able to:
1. Articulate how Solution Kinetics fits into the overall drug discovery and development process
2. Understand Solution Kinetic Terminology
3. Understand how to set up Differential Equations and Solve them for simple chemical reactions
4. Understand what the Kinetic Parameters (rate constants, etc.) mean
5. Understand how Approximations (Steady State, etc) affect experiment design
6. Improve Experiment Design
7. Select appropriate kinetic models to Solve Real Problems
8. Ask Better Questions

Who Would Benefit
This course is intended for both new and experienced professionals in the pharmaceutical and biopharmaceutical Industries, including, but not limited to: • Drug Discovery Directors/Associates/Scientists • Chemical Development Directors/Associates/Scientists • Preclinical/Non-Clinical/Clinical Development Directors/Associates/Scientists

Course Level
The course is designed such that all scientists no matter what your level of understanding of kinetics will benefit. The level of mathematical skills required to solve solution kinetic models is minimal for anyone who has studied college level algebra and calculus. It is anticipated that the participants of the course will be able to follow the mathematical operations and in the process develop a deeper understanding of solution kinetic models and an improved ability to interpret kinetic parameters.

Plate Based Label-Free Biosensors for Drug Discovery: A Whole New World

Course Instructors
Lance Laing, PhD, Consultant, SRU Biosystems, USA
Peter Lowe, PhD, Consultant, Biomolecular Interactions, UK
Rafael Fernandez, SRU Biosystems, USA
Kathy Dodgeson, PhD Astra Zeneca, UK
Alastair Brown PhD Astra Zeneca, UK

Course Summary
This one day course will provide an introduction to plate based label-free biosensor technology and detailed insight into applications thereof, presented by speakers at the forefront of their fields. The course will provide background on the available technologies, where the technologies are now, and how they might be applied in the near future. Focus will be placed on most useful applications with examples from fragment screening, cell screening, protein interaction screening, and next generation opportunities.

Course Objectives:
The course is designed to address the rising interest in the scientific pharmaceutical community in plate based label free technologies, providing users with empirical information with appropriate quantitative analysis.  Essentially, the course should answer whether plate based label free biosensors are a legitimate screening platform. The course will also provide a basis for comparison of two available formats (photonic crystal and impedance) and how they might be best utilized.  The course will also provide information for current users for the development of more advanced applications and will address the question “which stages of drug discovery and development is the technology ready for?”

Who Would Benefit
Persons curious about what the label-free “hype” is all about, technology assessment and acquisition teams, current users of label free platforms looking to work on more advanced applications, scientists trying to solve intractable screening issues with novel targets, scientists with problems arising from the use of labels that are looking for economical “ready for prime time” solutions without labels, scientists with orphan targets where label-requiring approaches are not available.

Course Level
All Levels.

Statistical Methods for In Vitro Assays in Drug Discovery

Course Instructors
Philip Iversen, Ph.D., Eli Lilly and Company
Sitta Sittampalam, Ph.D., Kansas Masonic Cancer Research Institute
Chris Moxham, Ph.D., Merck Research Laboratories

Course Summary
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.

Course Objectives
Upon completion of this course, participants will be able to (1) Understand and apply common assay performance measures; (2) Calculate false positive and false negative rates for high throughput screening assays; (3) Understand and apply appropriate statistical methods for estimating potency values; (4) Determine the reproducibility of potency assays using the minimum significant ratio (MSR) and control charting; (5) Apply correlation analysis to understand flow scheme connectivity; and (6) Understand the basic concepts of statistical experimental design for optimizing assays.

Who Would Benefit
This course is targeted to individuals interested in developing in vitro biological assays and use of these assays in drug discovery.

Course Level
All levels, but some experience with basic statistics (mean, standard deviation, p-value) and some experience with biological assays will be assumed.