A Universal Bio-Sensing Platform
Olivia Peters, Principal Investigator
Problems:
Current biosensor technology is extremely limited for several reasons.
Most research platforms focus on more traditional diseases or environmental
hazards instead of biothreats. Individual sensors look for a few very
specific threats (10-12 at most), and existing biothreat sensors are tested
only in the laboratory environment. Moreover, only well-trained clinical
technicians can use the sensors.
Objectives:
This project will develop a more generalized sensing platform to identify
a larger number of pathogens, leveraging microarray technology and automated
processing expertise. Steps will include identifying sequences that will
broadly attach to genetic material of various organisms, designing microarray
probes for the sequences, and designing algorithms to mine the microarray
data and classify the organisms in the environment.
Activities:
Microarray design will include selection of representative DNA sequences
to be used as microarray probes, applying modeling and simulation to identify
inappropriate sequences. Pattern classification: will involve application
of data mining and pattern recognition techniques to distinguish among
patterns for different agents. Multivariate pattern classification techniques
will be used, focusing on techniques that can handle large amounts of
data.
Impact:
The project will develop a handheld sensor that can automate sensing analysis
of any known biothreat agent, and has the capability to expand easily
to meet novel threats. A byproduct of this work will be identification
of the sequences that prove informative for distinguishing between organisms,
thereby providing a mechanism to compare different pathogenic agents.
Approved for Public Release: 06-1448
Presentation [PDF]
Bio-Threat Aircraft Warning System
Grace Hwang, Principal Investigator
Problems:
International airline passengers bringing biological warfare and other
infectious agents into the U.S. are a grave concern. Scenarios have been
posited where "carriers" are deliberately infected and sent to the US
as airline passengers, but infection need not be deliberate to raise public
health concerns: the avian influenza virus has the potential to cause
a pandemic.
Objectives:
Develop a rapid, reliable, reagentless, and miniature biosensor system
that can be deployed onboard aircraft to limit the spread of infectious
diseases and biological warfare agents and assist with containment strategies.
The envisioned sensor could be worn by flight attendants and/or strategically
positioned onboard (e.g., in seat-back, food cart, ECS system) to maximize
contact with airborne pathogens.
Activities:
Establish Type I and II error rates for a set of air transportation bio-defense
problems. A rapid, reliable, reagentless, and miniature biosensor that
can be deployed aboard aircraft will be prototyped. Two prototype sensors
will be built and a test plan will be written for biosensor testing in
a BSL-II chamber and in a grounded BSL-II B767 airliner mock-up.
Impact:
Rapid, reliable, onboard bio-threat sensing technologies will improve
border security, making it possible to respond to threats in real-time.
This will allow authorities to take appropriate actions to reduce the
potential impact of biological weapon attacks and pandemic outbreaks caused
by naturally occurring pathogens. This effort should be of interest to
the FAA, DHS S&T, and CDC.
Approved for Public Release: 07-0270
Presentation [PDF]
Camelid Nanobodies for Advanced Biosensing
Lynn Cooper, Principal Investigator
Problems:
Many biosensor platforms use immunomolecules called antibodies to detect
microbial pathogens and toxins. Standard, reagent-grade antibodies are
not heat stable and can degrade quickly under harsh environmental conditions.
Replacing these temperature-sensitive reagents with a new type of immunomolecule
that is environmentally stable could greatly increase the country's bio-sensing
capabilities.
Objectives:
The objective of this work is to develop and test prototype immunoassays
that are based on environmentally stable molecules. Our research hypothesis
is that small, toxin-specific immunomolecules derived from camelid species,
specifically llamas, can be efficiently produced and applied to the next
generation of field-deployable biosensors and detection/diagnostic platforms.
Activities:
Our research investigates the in vivo and in vitro properties of heavy-chain
antibodies produced by llamas. In short, toxin-specific antibodies will
be isolated from llamas, characterized, and then incorporated into an
existing hand-held assay format for comparison with standard antibody-based
assays.
Impact:
This work fills a critical need for robust field-deployable reagents for
antibody-based biosensor technologies. Its direct application is to biosensors
designed to detect microbial threat agents or their toxins. It has broader
importance for the fields of immuno-detection and immuno-diagnostics because
it demonstrates the feasibility of improving the basic component common
to all platform and assay types: the immunomolecule.
Approved for Public Release: 06-1523
Presentation [PDF]
Genomics for Bioforensics
Lynette Hirschman, Principal Investigator
Problems:
Bioforensics is used to distinguish between an outbreak caused by a naturally
occurring biological agent from that caused by an artificially introduced
bioagent, and further, between a known strain and an engineered organism.
Objectives:
The objective is to create a phylogenetics-based sample matching procedure
for attribution. Given the sequenced genome of an agent, such as influenza
or foot and mouth disease, our goals are to determine its most likely
source, based on comparison to a database of sequenced reference samples
and their associated time-space coordinates, and provide a probability
for that determination.
Activities:
We will start with one virus (influenza) and then generalize the methodology
and matching procedure for additional viruses and engineered viruses.
Our exploratory work used 200 influenza sequences (from the Institute
for Genomic Research using New York State data) to develop phylogenetic
trees to identify and explain outliers (e.g., travelers returning the
UK with a variant flu strain).
Impact:
The science underlying bioforensics supports related work on the modeling,
prediction and management of disease outbreaks, including applications
to epidemiology, public health surveillance, vaccine selection and development
of new vaccines and drugs.
Approved for Public Release: 07-0292
Human Monoclonal Antibodies for Neutralization
and Diagnosis of H5N1
Juan Arroyo, Principal Investigator
Problems:
Treatments for infectious diseases depend on vaccines, antimicrobials,
or passive transfer of antibodies. The source of antibodies may be polyclonal
(serum) or monoclonal. Monoclonal antibodies have yielded dramatic therapeutic
benefits in cancer treatment worldwide. This same power may be used to
bind and neutralize toxins, viruses, and bacteria. Our approach will produce
100% human monoclonals to avoid common side effects.
Objectives:
We will use a new methodology for producing human monoclonal antibodies
and assess its efficiency and capacity to generate antibodies against
the pandemic strain of avian influenza, the H5N1 virus. We will establish
the superior efficiency of this technology over competing technologies.
Our ultimate goal is to develop therapies to prevent H5N1 infection in
humans.
Activities:
We will differentiate B cells derived from human tonsils to yield clones
capable of secreting high-specificity antibody, screen for antibody binding
to the hemagglutinin protein of H5N1 virus, test for a subset that can
neutralize H5N1 virus, and map where on the hemagglutinin protein the
antibodies bind. We expect to find sites unique to H5N1 and universal
to influenza hemagglutinin proteins.
Impact:
We will develop a rapid and unique approach to producing monoclonal antibodies
that protect against pathogens and toxins. Rapid scale-up will produce
large amounts of antibodies for stockpiling. Antibodies can be used for
diagnosis or as injectable therapy for protection against lethal outcomes.
With cost-effective manufacturing, the approach may become a deployable
countermeasure of interest to national security and the U.S. population.
Approved for Public Release: 06-1405
Presentation [PDF]
Mathematical Modeling of Early Detection
of Infectious Disease Outbreaks: Toward Real-Time Surveillance
Mojdeh Mohtashemi, Principal Investigator
Problems:
Global health, threatened by emerging infectious diseases, increasingly
depends on the rapid acquisition, processing, and interpretation of massive
amounts of data. Despite moderate advancements in data acquisition, real-time
interpretation of data remains primitive. Early detection of infectious
disease outbreaks requires timely and accurate detection of real-time
epidemiological events for which current public health surveillance is
inadequately prepared.
Objectives:
We propose to develop mathematical and computational models for early
detection of unusual epidemiologic trends based on historical and real-time
data from collaborating hospitals and emergency departments, thus advancing
the art of surveillance from post-epidemic detection to pre-epidemic detection.
Such methods can be applied to a broad range of outbreaks of infectious
diseases, whether naturally occurring or maliciously instigated.
Activities:
We will acquire historical and real-time data from Harvard Medical School-affiliated
hospitals and other collaborating hospitals. We will develop spatio-temporal
and social contact structure models of early detection of infectious disease
outbreaks. These models will be validated using expert assessments and
standard statistical and simulation techniques, and incorporated into
AEGIS, a real-time surveillance system at the Children's Hospital, Boston.
Impact:
The project outcomes will provide the public health community with novel
methods for early detection of infectious disease outbreaks, while advancing
MITRE expertise in mathematical modeling of infectious disease and biosurveillance.
This work will position us to play a critical role in public health surveillance
and biodefense research and will support key MITRE sponsors.
Approved for Public Release: 05-0230
Presentation [PDF]
Pandemic Influenza: Containment and
Countermeasures in Closed Environments
Olivia Peters, Principal Investigator
Problems:
Infectious diseases thrive in crowded, confined spaces. Respiratory diseases
such as influenza are problematic in such settings. Understanding disease
transmission dynamics within these environments and making the correct
decisions during an outbreak are critical for both medical and command
personnel. This project addresses these issues through applied epidemiological
research coupled with infectious disease modeling on pandemic influenza
within naval settings.
Objectives:
Our mission partner is the USN Third Fleet. Using individual vessels as
self-contained units we will develop best practices for the prevention
and control of highly contagious disease outbreaks in closed settings;
test these practices with different disease scenarios, and use the results
to prepare a risk communication guidance packet for informing decision
makers and line commanders during real disease outbreaks.
Activities:
Using the Third Fleet as a test case we will apply modeling and simulation
techniques to test infection scenarios across a spectrum of population
and disease parameters. We will investigate containment across three levels:
individual ships, strike groups (movement between ships), and fleet level
(isolation or quarantine of entire vessels).
Impact:
Multiple entities within the defense, public health, and governmental
communities are tasked with drafting pandemic influenza response plans.
The results of this project give our military partners practical methods
for mitigating the medical and operational risks associated with an influenza
pandemic. These practices can be applied across leadership domains and
infectious disease outbreaks that require immediate medical surge capacity,
on-the-fly medical responses, and real-time decision making.
Approved for Public Release: 06-1449
Synthetic Biology: Engineering at
the Sub-Cellular Level
John Dileo, Principal Investigator
Problems:
The proliferation of weapons of mass destruction such as chemical weapons
(CW) poses a significant national security concern. However, the United
States has only limited ability to remotely monitor suspected facilities
for CW production. We believe that cellular mechanisms can be engineered
to generate a cell-based system that can detect chemical signatures associated
with CW production and produce a remotely observable signal.
Objectives:
We will develop the experimental and computational tools for the design
of biologic systems at the genome, protein, and system level. More specifically,
we will develop a biologically based sense-and-respond system for the
remote detection of CW production.
Activities:
We will accomplish our goals through an iterative cycle of computational
design, laboratory implementation and testing, and field validation. Specifically,
we will (1) use recently developed computational methods to design proteins
(receptors) that can detect small molecules associated with CW production,
(2) implement complex logical processing circuitry in DNA, and (3) couple
multiple protein detectors to DNA circuitry.
Impact:
This project will build on existing Technology Program investments in
the life sciences and extend MITRE's expertise into new areas (experimental
molecular biology and synthetic biology) that have the potential to assist
multiple sponsors. This will provide MITRE with new capabilities that
will allow us to better support current and future sponsors.
Approved for Public Release: 05-1506
Presentation [PDF]
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