|
Day One:
Thursday, January 29, 2004
|
Opening Forum |
|
Keys to Success in HCS
Sponsored by |
|
|
At the forefront of cell-based
assays is the emerging field of High Content Screening (HCS), based on the
analysis of the function, morphology, interactions, movement, and/or environment
of cells and their constituents. As an imaging-based technology, multiple
measurements can be derived from each assay and from each cell, contributing to
a wealth of information on which to base highly qualified decisions. This
interactive forum will identify the key challenges in HCS, focusing on issues
and challenges of integrating HCS technologies across a global organization,
choosing the right combination of assays and algorithms, and data reduction
strategies and tools for yielding decisions rapidly without sacrificing quality.
8:30-8:45 Welcoming Remarks from
Cellomics, Inc.
Mr. Daniel J. Calvo, President and
CEO, Cellomics, Inc.
8:45-9:45 Quantitative Image
Analysis of Embryonic Stem Cell Self-Renewal and Differentiation
Dr. Peter W. Zandstra, Canada Research Chair in Stem Cell Bioengineering,
Institute of Biomaterials and Biomedical Engineering, University of Toronto
Embryonic stem (ES) cells have attracted much attention as a possible source of
functional cells for regenerative medicine. This presentation will review our
recent progress in the development of a high throughput and high content image
analysis platform for the kinetic analysis of ES cell fate decisions.
9:45-10:15 Coffee Break with
Poster and Exhibit Viewing
10:15-11:00 Unlocking the Value
in Your HCS
Mr. Joe Zock, Senior Director of HCS User Services, Cellomics, Inc.
How do you capture value in your HCS assays? In this presentation, we touch upon
key considerations that will streamline your HCS assay development, where
multiparameter design and validation are critical. This will lead into a
discussion of HCS data storage, manipulation, management and visualization where
the true "end game" is decision support for the drug discovery
process.
11:00-11:45 Integrating
Information Across the Biological Landscape
Dr. James M. Gill, Group Leader, Discovery Data Technologies,
Bristol-Myers Squibb
The biotechnological revolution is now in full swing and we have access to
the tools and technologies which make High Content Screening possible.
However, collecting lots of data is not sufficient. Successful drug discovery
depends on placing HCS data in a biological context and communicating that
information across a diverse community. We will discuss informatics tools we are
developing to provide HCS analysts access to a diverse set of information from
the high level surrounding target function to the simple facts about the
specifics of reagent preparation. We will also discuss various approaches we are
taking to integrating the incredibly rich information generated by HCS with the
chemical and genomic information used throughout the rest of organization. |
11:45-1:10 Lunch (on your
own)
High-Content
Screening: Integration into HTS
1:10-1:15 Chairperson's Opening Remarks
Dr. Ralph J. Garippa, Research Leader, Roche Discovery Technologies,
Hoffmann-La Roche, Inc.
1:15-1:45 Merging High-Content Screening (HCS)
With High-Throughput Screening (HTS) Systems
Dr. Bonnie Howell, Senior Research Biochemist, Automated Biotechnology,
Merck and Co.
There are multiple success stories using HCS for target validation,
secondary screening through lead optimization, as well as the use of HCS at
later stages within the drug discovery/drug development process. Recent data
in the field indicates there is an intensifying effort to expand the HCS arena
into one that fulfills HTS needs. Given the breadth of HCS and its present yet
nominal integration into HTS, many new questions require answers before
embarking on such a path. These questions center on what type of HCS/HTS
instrument (with its complementary robotic automation) is needed, the breadth
of information technology within the global organization, and the specific
drug discovery needs of the individual departments. All in all, the most
significant factor in successfully integrating HCS into HTS is perhaps the
core of cross-functional teams needed to seamlessly implement, execute, and
nurture the organization through its early adoption. In conjunction with
management support, the merging of HCS and HTS will certainly continue to
occur, thus opening a new horizon for the primary screening of drug targets.
1:45-2:15 Integrating High-Content Assays
With Early Lead Identification Strategies
Dr. Berta Strulovici, Executive Director, Automated Biotechnology,
Merck and Co.
Recent advancements in genomics have produced a wealth of new molecular
targets for drug therapy. Combined with the availability of large chemical
libraries, the current challenge is to identify high-quality lead compounds
for many therapeutic targets, rapidly and cost-effectively. The emergence of
new imaging technologies, coupled with powerful computer software, as well as
advances in fluorescent protein-based optical sensors and cell-permeable,
organelle-specific probes, begin to enable the simultaneous acquisition of
information about multiple cellular processes. The ability to visualize gene
expression, protein interactions, subtle changes in subcellular localization,
and proteolysis, is becoming a key part of the arsenal available to the HTS
scientist in search of high-quality lead compounds.
2:15-2:45 Assay Development and Case History
of a 32K Biased Library High Content Screen on the ArrayScan Platform
Mr. Oscar Trask, Senior Associate Biochemist, Lead Generation Biology,
Eli Lilly and Co.
Advances in fluorescent-based reagents and multicolor fluorescence
microscopy have provided a means to multiplex the study of target proteins
within cells. The emergence of automated, multi-mode microscopy platforms with
high-resolution optics, and powerful image analysis software, has reached
throughputs compatible with drug discovery. The development of a mitogen-activated,
protein kinase-activated, protein kinase-2 translocation assay on the
ArrayScan platform will be described, and the case history from a 32K-biased
library High Content Screen will be presented.
2:45-3:25 Refreshment Break with Poster and
Exhibit Viewing
Secondary Screening and ADME/Tox
3:25-3:30 Chairperson's Opening Remarks
Ms. Ann F. Hoffman, Senior Principal Scientist, Cell-Based HTS,
Hoffmann-La Roche, Inc.
3:30-4:00 Evaluation of Early Markers of
Hepatocellular Toxicity in Formalin-Fixed Tissues Using Laser Scanning
Cytometry
Dr. Amy Shen, Scientist, Pathology, Pfizer, Inc.
Laser Scanning Cytometry (LSC) is a hybrid technology which combines the
advantages of fluorescence microscopy and flow cytometry. The goal of this
presentation is to describe the evaluation and validation of multiple early
markers of hepatocellular toxicity in formalin-fixed paraffin embedded tissues
using the LSC. The data was compared to concurrent gold standards such as
microscopy or biochemical end points.
4:00-4:30 Changing the Paradigm: Early
Contributions by HCS in the ADME/Tox Area
Ms. Ann F. Hoffman
The presentation will focus on how toxicity assays are being repositioned
towards an earlier stage in the drug discovery process by using HCS. Data will
be presented illustrating the application of various molecular probes on two
HCS platforms in screens that vary across multiple cell types. The challenges
and benefits of how this additional information can lead to better decisions
for discriminating individual compounds and lead chemistry series will be
discussed.
4:30-5:00 HCS As Means of High-Throughput
Predictive Toxicological Screening
Dr. Edward Ainscow, Research Scientist, Enabling Science and Technology
and Informatics, Advanced Science and Technology Laboratory, AstraZeneca
R&D
Cell-based imaging assays are ideally suited to early toxicity screening
as they offer the flexibility necessary to analyze the diverse cellular events
leading to cell death. Information on compounds may be gained through assays
for a specific class of toxicity, but also through off-target effects within
HTS. The power of these assays can be seen when multi-parametric readouts are
combined with advanced informatics tools enabling predictive, mechanistic
screening of cytotoxicity.
 |
5:00-5:45
HCS "Dream
Machine"
Chairperson: Dr. Ralph J. Garippa
Panelists:
- Dr. Paul A.
Johnston, Research Scientist, Sphinx Laboratories, Eli Lilly and
Co.
- Dr. Berta Strulovici,
Executive Director, Automated Biotechnology, Merck and Co.
- Dr. Jeffrey Price,
Founder and Chief Scientist, Q3DM Inc., and Associate Research
Scientist, Dept. of Bioengineering and Whitaker Institute of
Biomedical Engineering, University of California, San Diego
- Dr. Martin Gluch,
Head of Product Management, Molecular Medicine Group, Carl Zeiss
Jena GmbH
Discussion Topics:
- Should one machine
do it all? Should it be modular and expandable? Should there be
various models of increasing complexity? Should there be on-board fluidics?
- The filters and
fluors: Continue with the usual suspects or should we prepare for
the future? How wide for Ex/Em?
- The light source:
Should we use laser or lamp? Is brightfield or phase-contrast
necessary? Does fast autofocus need a separate source?
- The optics:
Numerical aperture, depth of field, and magnification issues. Full
or quasi-confocal? Is water or oil immersion possible and/or
needed?
- Image algorithms:
Open access or turnkey? Amount of end-user choices? How to offer
and price them?
- The plateware:
Plastic or glass? Is there a necessity for imposition of an SBS-type
standard on HCS plates?
- Price: Who is
willing to pay and how much? Pharma, Biotech and Academia.
Co-development consortiums vs. free market?
|
|
Facilitated
Networking
5:45-7:00 Wine & Cheese Reception with
Roundtable Discussions
Discussion Topics and Facilitators:
- High-Content Screening (Dr. Ralph J. Garippa,
Research Leader, Hoffmann-La Roche, Inc.)
- ADME/Tox (Ms. Ann F. Hoffman, Senior
Principal Scientist, Cell-Based HTS, Hoffmann-La Roche, Inc)
- Target Validation
(Dr. Judy Masucci, Dir Product Marketing, Product Marketing, Cellomics,
Inc.)
- Assay Development (Dr.
Jonathan Lee, Director, Discovery Technologies, Eli Lilly and Co.)
- HCS Informatics (Dr. J. Paul Robinson,
Professor of Immunopharmacology and Biomedical Engineering, Purdue
University; and Mr. Mike Esterman, Sr. Information Consultant, Discovery IT, Eli Lilly and Co.)
- "Which instrument should I buy?"
(Dr. Paul A. Johnston, Research Scientist, Sphinx Laboratories, Eli Lilly
and Co.)
How Does Facilitated Networking
Work?
Sign up for one discussion topic. A week before the
conference, you will receive the names and e-mail addresses of other
conference attendees interested in the same topic. This allows you to
initiate the discussions or arrange meetings in advance. During the
networking session, you are welcome to move freely between the
roundtables. The discussion facilitators will present an update the
following morning. (You must be a registered attendee to
participate.)
|
|
