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PROGRAM
Tuesday, August 26
4-6pm Early Registration
Wednesday, August 27
7:30am Registration
8:20 Chairperson's Opening Comments
Dr. Ernest T. Takafuji, Director, Office of Biodefense Research
Affairs, National Institute of Allergy and Infectious Diseases
8:30 Preparedness and Response in
Biowarfare and Bioterrorism
Dr. David R. Franz, Vice President, Chemical and Biological Defense,
Southern Research Institute
Throughout history, technologies beneficial to man have been abused as
weapons; biology is no exception. Biology as a weapon may be unique,
however: facilities, equipment and people are dual-use; we cannot detect
agents in the air in real-time, as we can chemicals; attribution is
extremely difficult and, in the case of biological terrorism, the
footprint of the production facility and the weapon itself are very
small. We must both prepare to respond to a biological attack on one of
our cities and use all means to deter the attack before it occurs. Dr.
Franz will discuss the problem and an integrated set of solutions.
9:00 The Microbial Genetics and
Forensics Initiative
Dr. James M. Robertson, Research Biologist, Counterterrorism and
Forensic Science Research Unit, Laboratory Division, Federal Bureau of
Investigation
The FBI supports and hosts the Scientific Working Group on Microbial
Genetics and Forensics (SWGMGF), composed of multidisciplinary experts
in microbiology and bio-terrorism. Some of the topics the participants
of the SWGMGF discuss include the development of a DNA database of
available genetic information, research needs to identify and
fingerprint threat agents, criteria for validating new tests, and
criteria for developing new analytical tools for rapid identification in
the field. The SWGMGF will establish guidelines for quality assurance
and quality control to provide validity as well as standards for
microbial fingerprinting that go further than those of the typical
clinical laboratory. The SWGMGF is modeled after the successful
Scientific Working Group on DNA Analysis Methods (SWGDAM), which was
established to develop and ensure a high quality for human forensic DNA
analysis. This presentation will provide an overview of the endeavors of
SWGMGF to address the requirements of law enforcement agencies to
investigate, attribute, and deter criminal dissemination of biological
agents.
9:30 Advanced Concept Technology
Demonstrations
Dr. Theodore K. Barna, Assistant Deputy Under Secretary of Defense (ADUSD),
Chem/Bio/Nuclear & Radiological Technology
Advanced Concept Technology Demonstrations (ACTD's) exploit mature and
maturing technologies to solve important military problems. A declining
budget, significant changes in threats, and an accelerated pace of
technology development have challenged our ability to adequately respond
to rapidly evolving military needs. In addition, the global
proliferation of military technologies, resulting in relatively easy
access to these technologies by potential adversaries, has further
increased the need to rapidly transition new capabilities from the
developer to the user.
10:00 Coffee Break, Poster &
Exhibit Viewing
10:30 Commercialization of Emerging
Technology Forum NIAID's Continuing Role in Biodefense Research:
Partnerships, Programs, and Opportunities
Dr. Ernest T. Takafuji
The National Institute of Allergy and Infectious Diseases continues its
prominent role in promoting and supporting quality biomedical research
directed at biological threats facing the nation. In response to dangers
associated with bioterrorism, a variety of efforts aimed at enhancing
the research base of the nation with involvement of federal departments
and agencies, academic institutions, and industry have resulted in new
initiatives in research and development leading to new products.
11:00 Innovations in Nanotechnology
Ms. Jennifer Fonstad, Managing Director, Draper Fisher Jurvetson
One of the reasons that nanotechnology has relevance, beyond being a
simple reference to a length scale, is that much of the learning that
compounds at this particular frontier has broad applicability across
diverse industries and scientific pursuits. Rich horizontal
conversations are flourishing in labs and academic centers, and to great
effect. Most of the disruptive innovations in any industry will come
from left field, from the edge, and from the interstices between formal
academic disciplines. Nanotech is the nexus for the sciences. Our
discussion will explore how current research in nanotechnology will
inform and influence future military, biodefense, and security
applications.
11:30 Panel Discussion
12:00 Lunch on your own
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EMERGING TECHNOLOGY
SHOWCASE
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1:20 Chairperson's Remarks
1:30 Detecting Microbial Signature
Profiles Using Gene Expression Time Series Analysis
Dr. Ben Goertzel, Chief Executive Officer, Biomind, Inc.
The early effects of pathogen infection are often difficult to
distinguish from more innocuous medical conditions - meaning that, by
the time the presence of an infection becomes obvious, the optimal time
for intervention may have passed. One approach to early detection of
pathogen infection involves microarray technology. After measuring the
gene expression profiles of a potentially infected person's cells at a
series of time points, one checks whether the series of profiles
displays the temporal response patterns characteristic of
pathogen-infected cells. In some cases there are particular genes whose
expression level distinguishes infected from uninfected cells; but in
many cases, one must look for subtler differentiating patterns involving
multiple interrelated genes. In general, this approach requires the
application of some fairly sophisticated data analysis algorithms, drawn
from the areas of time series analysis and supervised categorization. In
this talk we will review the leading approaches to carrying out this
sort of data analysis, discussing statistical and machine learning
approaches, and also advanced AI approaches utilizing background
information derived from biological databases. As a practical example,
we will show results from several different analytical techniques
applied to time series, gene expression data from cells infected by the
Bordetella pertussis bacterium.
1:45 The Artificial Lymph Node for
Biodefense
Dr. William L. Warren, President, Sciperio, Inc.
The Artificial Lymph Node (ALN) is a nine-team member effort to create
an engineered, three-dimensional (3D), tissue engineering (TE) scaffold
that incorporates cell differentiation cascades that enable the
formation of basic, functional, biological tissues, particularly
immunological tissues. The ALN acts like a 3D, dendritic,
cell-populated, engineered tissue construct (ETC) that is designed to
act as a "vaccine" in vivo, allowing rational control of the
hosts' immune responses, through temporal and spatial control of
dendritic cell (DC) activation and migration, as well as programming of
DC precursor differentiation within designer ETCs. It is designed for a
number of different vaccines for biowarfare defense depending on the
antigen and the DC maturation signals used in the construct.
2:00 Rapid DNA Analysis Systems for
Pathogen Surveillance
Dr. Houng-Yau Mei, Vice President, Operations, Rubicon Genomics, Inc.
Rubicon's objectives in pathogen surveillance are to develop and
commercialize, jointly with partners, a universal detection system to
detect all known, newly emergent, or bio-engineered pathogens with high
sensitivity, accuracy and specificity. Rubicon's proprietary technology,
OmniPlex™, has been demonstrated as a powerful DNA amplification and
analysis tool for genetic studies of human or microbial genomes. In
particular, applications in targeted sequencing, whole genome, or highly
multiplexed amplification and sub-genome analysis have been shown to
exceed the capabilities of any existing methodologies for in vitro
nucleic acid amplification or diagnostics. Rubicon's OmniPlex technology
can be integrated with leading-edge detection systems into a gene-based
biosurveillance platform for rapid identification and quantification of
pathogens (ground facility, water or air-borne). With such an early
warning system in place for continuously monitoring for biohazardous
agents, appropriate actions can be taken, with maximalresponse time, to
counter the bioterrorist threats most effectively before disastrous
consequences occur.
2:15 Supersensitive P-Chips for
Detection of Biowarfare Agents
Dr. Andrzej K. Drukier, Chief Executive Officer and Chief Science
Officer, BioTraces, Inc.
We are developing the P-chips/MPD with sensitivity about 100-fold higher
than any previous multi-target immunological methods. Detection of below
1 pathogen/liter of air seems possible. Recent results on MPD-enhanced
immunodiagnostics and proteomics will be provided.
2:30 Molecular Recognition Using
Micromechanical Sensors
Dr. Thomas Thundat, Senior Scientist and Group Leader, Oak Ridge
National Laboratory
Extremely sensitive and highly selective chemical and biological
detectors can be developed using micromachined and mass-produced
microcantilevers. Microcantilever resonance response, such as resonance
frequency, deflection, and Q-factor, undergo variation due to molecular
adsorption. We have demonstrated a number of sensors for chemical agents
and biological weapons using a microcantilever platform. An array-based
approach offers the flexibility of multi-analyte detection using a
single sensor platform.
2:45 Refreshment Break, Poster &
Exhibit Viewing
3:30 Fiber Optic and Two-Dimensional
Array Biosensors for Biodefense
Dr. Chris Rowe-Taitt, Research Biochemist, Naval Research Laboratory
Researchers at the US Naval Research Laboratory have developed two
biosensors capable of detecting multiple pathogens and toxic
biomolecules in less than 15 minutes. The fiber optic biosensor RAPTOR
is a 14 lb., battery-powered, fully automated unit that can be operated
in the field and is now commercially available through Research
International (Woodinville, WA). RAPTOR can test for up to 8 different
analytes simultaneously. The array biosensor, still a laboratory
prototype, can detect up to 9 different agents simultaneously and is
considered to be the next generation of immunosensor. Both systems can
be used for real-time monitoring of binding events and have been used to
detect and measure analytes in a variety of sample types, including
foodstuffs, body fluids, and environmental samples (e.g., ground water,
extracts from smoke, and suspensions of pollen, sand, clay).
3:45 Rapid, Multiplex, Fluorescent
Array Tests for Biodefense
Dr. Kodumudi Venkateswaran, Advanced Diagnostics Group Leader,
Lawrence Livermore National Laboratory
We developed a novel, fluorescent array, multiplex assay for the
simultaneous detection of agents causing anthrax, plague, botulism etc.
This assay performance is comparable to gold standard immunoassays. The
reliability, cost effectiveness, and ease of use makes this assay most
attractive for ready use of biodetection.
4:00 A Reagent, Programmable,
Universal Platform for Sensitive, Reproducible, Repeatable, High Sample
Throughput Measurement of RNA and Protein Signatures
Dr. Bruce Seligmann, President, High Throughput Genomics, Inc.
The ArrayPlate platform and performance is ideally suited for the
detection of BioAgents and host exposure and response. A reagent,
programmable, universal array is employed, which means that reagent
packs can be used to change assays in the field without any change in
hardware or plastic disposables. The ArrayPlate platform is universal,
providing measurement of RNA, DNA, or proteins. The ArrayPlate does not
use PCR and therefore avoids the need/difficulty to extract RNA. The
ArrayPlate provides sensitivity to measure low expressed genes without
signal amplification, to measure RNA from samples as small as 1,000
cells (e.g. a drop of blood), and high expressed genes from as few as 50
cells, with whole assay reproducibility in the 10-20% CV range, 90%
repeatability, and to do so on thousands of samples per day. Signal
amplification reagents provide even greater sensitivity for the
detection of critical, low expressed genes. The ArrayPlate measures an
entire molecular signature and therefore not only can identify agents
and differentiate responses, but addresses a third major issue, namely,
the panic that is created by false positive readings.
4:15 Sensitive, Hand-Held Assay for
Detection of BioThreat Agents
Dr. Robert Daniel, Director of Operations, ANP Technologies, Inc.
We have developed hand-held immunoassays for the detection of all
classes of biothreat agents, including those of top priority for the
U.S. Department of Defense. Using a nanomanipulation technique, these
assays show 10 to 100-fold greater sensitivity than currently available
immunoassays. Work is being initiated to detect markers of human
exposure to biothreat agents using this same technology.
4:30 Lipoparticles for Drug Discovery
and Diagnostic Applications in Biodefense
Dr. Benjamin Doranz, President and Chief Scientific Officer, Integral
Molecular, Inc.
Integral Molecular is a biotechnology company that is using a new
technology, the lipoparticle, for biodefense diagnostic applications.
Lipoparticles allow membrane proteins, including G-protein coupled
receptors and ion channels, to be purified away from the cell while
preserving the membrane protein's structural integrity. Membrane
proteins serve as the targets for most infectious pathogens.
Lipoparticles are now being paired with optical biosensors to
characterize ligand, protein, and antibody interactions, and for the
detection of biodefense pathogens.
4:45 Experiences with Grid-Based,
Virtual Screening Techniques
Dr. Scott D. Kahn, Chief Scientific Officer, Accelrys Inc.
The implementation of virtual screening methods on grid computing
technologies is well known, and has seen significant evolution in its
short history. Most important have been the advances in the accuracy of
the predictions, as mandated by the enormous amount of processing that
throughput afforded even a modestly sized grid. This presentation will
discuss these issues through the experiences gained on the search for
potential drugs to cure anthrax and smallpox. The latter of these
projects is ongoing, providing a convenient forum to discuss the future
trends in grid-based, virtual screening efforts.
5:15 Reception, Poster Viewing, and
Facilitated Networking Roundtable Discussions
(topics and discussion leaders to be announced)
6:15 Close of Day One
Thursday, August 28
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DETECTING AND
CHARACTERIZING
BIOLOGICAL AGENTS
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8:20 Chairperson's Remarks
Dr. Nitish V. Thakor, Professor, Biomedical Engineering, Johns
Hopkins University School of Medicine
8:30 Diagnostic Test for SARS: Lessons
Applied to Biodefense
(speaker to be announced)
9:00 Multiplexing Real-time PCR
Dr. Nick M. Cirino, Director, Biodefense Laboratory, New York State
Department of Health, Wadsworth Center- Axelrod Institute
Multi-analyte analysis is the only way to make BT surveillance cost and
time effective. The NYS DOH Biodefense laboratory has developed
multiplex assays for select agents, which allow for rapid,
high-confidence analyses.
9:30 Creating a Testing Environment
for Biodefense Applications
Dr. David H. Brown, Director, Manager, Biotechnology
Commercialization, Battelle
Memorial Institute
Over three decades, Battelle has worked with the government and private
industry to develop technology for chemical and biological detection
systems. Our history provides us a unique perspective on the limitations
associated with development and testing of detection systems. Recent
domestic events have radically modified Battelle's development plans for
rapid and accurate biological detection systems. Our programs have
evolved from developing biodetection systems designed to support the
warfighter to increasing developmental efforts on systems that can aid
in the protection of civilian populations. Testing and validation
regimens must be designed to meet client specific needs. Tradeoffs
between detection efficacy and cost are often necessary. We continue to
search for new methods of detection that expand our ability to more
rapidly detect and identify biological threat organisms. This
presentation will discuss the elements of biodetection and the test
infrastructure required to validate new systems.
10:00 Coffee Break, Poster &
Exhibit Viewing
10:30 Quantitative Flash Detection of
Potential Pathogens, Bacterial Spores, and Bioterrorism Biomarkers from
Complex Clinical and Environmental Matrices
Dr. David C. White, Center for Environmental Biotechnology,
University of Tennessee
A system involving "flash" high temperature, high pressure,
solvent extraction of microbial water-exposed biofilms, clinical
specimens, filter retentates, potential agent sources, and other complex
matrices has been shown to be capable of rapidly defining potential
threat situations. Lipid biomarkers characteristic of pathogens,
hydrophobic, membrane-active toxic, or pharmaceutically active agents
can be detected quantitatively and often chemically identified by tandem
mass spectral analysis at near part per trillion sensitivities.
Protecting drinking water involves large volumes of reservoirs,
treatment centers and distribution systems that generate a great
dilution of the potential pathogens and toxicants but makes system
monitoring difficult. Our solution to dilution-compromised, monitoring
effectiveness is to utilize the propensity of pathogenic microbes and
toxicants to concentrate at surfaces in the ever-present biofilms, whose
effectiveness can be increased by a specific biofilm-amplifying
technology. After "flash" sequential extraction, rapid
analysis of these natural biofilm "collectors" or other
environmental matrices yields neutral lipids, intact phospholipids, and
after acid hydrolysis of the lipid-extracted residue, the specific beta-hydroxy-myristic
acid characteristic of the lipopolysaccharide of Gram-negative pathogens
or the spore specific bacterial biomarker, 2, 6-dipicolinic acid.
Generation of electron-withdrawing derivatives allows detection of
components containing alcohol, amine, carboxylic acid, or ketone
moieties with ultrasensitive, cost-effective, tandem mass spectrometry.
This fascicle analysis takes less than an hour and is capable of
differentiating microbial bioterriorism attacks from threats or hoaxes
by defining a potential microbial pathogen or most toxic agents.
11:00 Complex Biosignatures of
Infection
Dr. C. Richard Lyons, Associate Professor, Medicine/Oncology,
University of New Mexico Health Sciences Center
We are studying diagnostic and prognostic strategies that interpret and
detect biosignatures representing the language of the host early defense
response with the end results indicating the health status of the body
and detecting changes consistent with infection. Our hypothesis is that
by using broad based detection systems that detect multiple signals
coupled with pattern recognition computer analysis for interpretation we
will determine the earliest reproducible pattern(s) indicating that an
infection has occurred. Biosignatures are likely to provide significant
diagnostic and prognostic data regarding clinical outcome during the
course of infection as well as applications toward clinical validation
of anti-BW products.
11:30 Panel Discussion
12:00 Lunch on your own
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STIMULATING IMMUNE
RESPONSE, DEVELOPING VACCINES & THERAPEUTICS
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1:20 Chairperson's Remarks
Dr. Arthur M. Krieg, Chief Scientific Officer, Coley Pharmaceutical
Group
1:30 Novel Challenges in Clinical
Development of Highest Priority Agents
Dr. Steven Rosenthal, Medical Officer, Center for Biologics
Evaluation and Research, U.S. Food and Drug Administration
There is active development of new vaccines (as well as other biologics
and drugs) that are needed to counteract the effects of a potential
bioterrorist or biowarfare event on the U.S. domestic population and
military forces. Regulation of products to protect against potential
biowarfare agents poses unique challenges, since the usual measures of
efficacy that require exposure to natural disease currently may not be
possible due to epidemiologic and ethical reasons. To help address this
issue, the FDA has published the Animal Rule, intended to address
certain efficacy issues for new agents for use against lethal or
permanently disabling toxic substances. Recent product development
activity has focused on Bacillus anthracis (anthrax) and variola major
(smallpox), agents that are considered highest priority in posing a risk
to national security. FDA resources exist to assist vaccine developers
with regard to the novel challenges posed in clinical development of
these products.
2:00 Pathogen-Specific Recombinant
Human Polyclonal Antibodies: Biodefense Applications
Dr. John Haurum, Chief Scientific Officer, Symphogen, Inc.
Symphogen is developing a novel antibody technology platform to develop
pathogen-specific recombinant human polyclonal antibodies. This
technology holds important promises in replacing blood-derived
gammaglobulin products for therapy or prevention of communicable
diseases caused by infectious microorganisms or biotoxins. In
particular, the technology would be applicable against anthrax,
botulinum toxin, hemorrhagic viruses, and smallpox.
2:30 Development of Novel Alphavirus
Vaccines Using DNA Shuffling
Dr. Christopher Locher, Project Leader, Maxygen, Inc.
The VEE (Venezuelan Equine Encephalitis), EEE (Eastern Equine
Encephalitis), and WEE (Western Equine Encephalitis) alphaviruses are
important bio warfare agents, and current vaccine strategies do not
provide cross-protection against all three viruses. To develop a more
effective and cross reactive DNA vaccine, we have shuffled the envelope
genes of all three viruses together to generate chimeric clones. We
found that after DNA immunization this approach may provide high titers
of cross-protective and virus neutralizing antibodies.
3:00 Refreshment Break, Poster &
Exhibit Viewing
3:30 Development of a Novel Platform
for Targeted Delivery of Mucosal Vaccines
Dr. David Lo, Vice President, Integrative Biology, Digital Gene
Technologies, Inc.
Rapid development of new vaccines to protect from emerging infectious
diseases will require new methods for efficient delivery of recombinant
antigens and effective stimulation of protective immunity. Toward this
goal, we looked to the basic elements of mucosal immunity, using TOGA®
open system, gene expression profiling to identify genes responsible for
the surveillance of intestinal and nasal passages. We identified several
candidate receptors that appear, to be critical to epithelial transport
of antigens to intestinal Peyer's Patches, and are presently developing
ligands to these target receptors as a novel platform for delivery of
synthetic vaccines. This biology-based approach to vaccine development
will enable efficient delivery of synthetic vaccine antigens directly to
cells of the mucosal immune system, and rapid development of new vaccine
formulations.
4:00 A Surrogate T-Cell Marker for
Biodefense Vaccine Development and Immunotherapy: The Cylex In Vitro CMI
Technology
Dr. Richard J. Kowalski, Manager, Product Development, Cylex
Incorporated
Many vaccines elicit antibody responses that provide effective
protection; however, antibodies are not effective against all
microorganisms (i.e. tuberculosis, malaria, hepatitis C), and T
cell-dependent responses are required to prevent disease. Cylex has
developed an in vitro assay that directly measures antigen-specific
cellular immune responses of CD3+ lymphocytes, that has direct
application to the assessment of vaccine efficacy. This study summarizes
the immune response of individuals to foreign antigens (anthrax,
influenza, CMV and tetanus) and the effects of immunosuppressive therapy
on cell-mediated immunity. Volunteers with known natural exposure or
vaccination showed significant responses; whereas, those not exposed,
unvaccinated or immunosuppressed showed no response.
4:30 Panel Discussion
5:00 Close of Conference
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