| 2006 Technology
Symposium > Biotechnology
Biotechnology
The Biotechnology TAT focuses on biomedical research as it intersects
with information technology, security, national intelligence, and defense.
This includes biomedical and neuroscience informatics, computational biology
and biologically inspired computation, biosecurity and biodefense, and
biosensing (including both sensing of biological agents and biologically-based
sensors).
Biologically-Inspired Cognitive Architectures (BICA)
Brandon Minnery, Principal Investigator
Location(s): Washington
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Diagnosis of a Bio-Warfare Agent
Olivia Peters, Principal Investigator
Location(s): Washington
Problem
It is difficult to determine if a biological attack has taken place because the technology does not exist for rapid and early diagnosis of a biowarfare attack. Currently, we have no information infrastructure for efficient storage of relevant data, no method to identify the specific genes affected by the pathogens, and no algorithms for analysis and classification of unknown data.
Objectives
The objective is to develop a classifier to quickly identify if a warfighter has been exposed to a biowarfare agent, the agent used, and a timeframe for this exposure. We will do this by coordinating and managing a large amount of microarray data, performing feature extraction and dimensionality reduction, and designing a classifier to determine cellular pathogen exposure.
Activities
The focus in year one was developing feature selection and classification methods that could differentiate individual biological and chemical warfare agents from controls subjects. Year two has moved from a binary distinction to a multi-class decision, classifying a sample by which agent it was exposed to.
Impact
The major impact will provide a rapid evaluation of exposure (agent and time). Additional impacts will include an ability to pinpoint the source of exposure, determine potential therapeutic techniques, and begin to understand unknown pathogens through their closeness to known agents. This project will add to and complement MITRE's existing biological expertise.
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Genomics for Bioforensics
Lynette Hirschman, Principal Investigator
Location(s): Washington and Bedford
Problem
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.
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Mathematical Modeling of Early Detection of Infectious Disease Outbreaks: Toward Real-Time Surveillance
Mojdeh Mohtashemi, Principal Investigator
Location(s): Washington and Bedford
Problem
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.
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Multiscale Mathematical Modeling for Epidemic Control
Ming Wang, Principal Investigator
Location(s): Washington
Problem
Development of control strategies for infectious diseases must take account of complex ecological and social dynamics. Properly developed models must integrate knowledge from subject matter experts (SMEs) in diverse disciplines, make assumptions explicit, provide for meaningful dialogue, and give quantitative insights to the scale and dynamics of an epidemic as well as the performance of various control strategies.
Objectives
The objectives of this research include the development of a general Agent-Based Model (ABM) that can serve as the basis for capturing, in a reproducible form, the knowledge and experience of subject matter experts and decision makers. We will also develop an appropriate analytic structure that can incorporate spatial and continuous representations of disease transmission together with ABMs.
Activities
We will expand and refine the community ABM developed in previous efforts by making it more flexible, soliciting feedback from SMEs and improving user interfaces. We will research information about travel and human mobility (e.g., commuter flow, air travel), examine the temporal and spatial scales of disease transmission, and develop a multi-scale analytical framework for modeling disease transmission and evaluating control options over space and time.
Impact
This research and the proposed multi-scale modeling framework address issues of interest to various MITRE sponsors: HHS/Office of Public Health Emergency Preparedness, CDC, DHS, and the Intelligence Technology Innovation Center (ITIC).
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Neuroinformatics
Monica Carley-Spencer, Principal Investigator
Location(s): Washington
Problem
The neuroscience community is accumulating a vast amount of human brain mapping data that does not reach its full scientific potential because it is generally confined to the originating lab. While data may exist that a researcher could use to explore a hypothesis, the investigator may be unaware of it or does not have access to it.
Objectives
The overall goals of this research, conducted in conjunction with an external NIH grant, are to design, prototype, and evaluate an information infrastructure to help realize the full potential of a growing store of human brain mapping data. In this initial undertaking, we focus on a system that enables the analysis, exploration, and dissemination of structural magnetic resonance imaging data.
Activities
We have made significant progress toward developing image retrieval capabilities that will augment the NeuroServ data management platform developed under the NIH grant for managing and sharing neuroimagery. These capabilities include content-based image retrieval, or query-by-example, and image quality screening. Image features and metrics are tested with both synthesized and real MRI provided by collaborators in the NIH research community.
Impact
This project provides an important public service to the neuroscience research and clinical communities. But the problems facing these communities are not unique; they are isomorphic to those facing many of MITRE's traditional sponsors who must manage and exploit large quantities of imagery. We expect our research to transition readily to DoD, federal law enforcement and intelligence community sponsors.
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Pathogen Capture Using Floating Films
Elaine Mullen, Principal Investigator
Location(s): Washington and Bedford
Problem
Recent events have heightened awareness of the need to protect drinking water against bioterrorist threats. Contaminated surface water can contribute to the spread of infectious disease through human and animal populations. To counter these threats, scientists need an inexpensive, unobtrusive method of concentrating and detecting harmful microbes and toxins in drinking water reservoirs and surface waters worldwide.
Objectives
We will design a prototype film to collect and concentrate specific pathogenic bacteria at the surface of water. We will optimize and quantify the film's stability, specificity, and efficiency under various environmental conditions and concentrations of organisms. During the course of our research, we will measure physical properties that could lead to the development of a remote water surveillance capability.
Activities
At Johns Hopkins Applied Physics Lab we will float designer films on water containing a mixture of pathogenic and harmless bacteria. A world-class team of experts will evaluate the experimental protocol and test results. We will measure the effects of varying micelle size and composition, pathogen concentration, and mixing time, and will periodically measure spectral characteristics of the films.
Impact
Films and micelles synthesized from lipids and glycoproteins offer an affordable and inconspicuous means of selectively concentrating pathogens at the surface of drinking water reservoirs. This technology may provide the basis of an affordable and unobtrusive large-area remote water surveillance system that could be licensed into commercial instrumentation. MITRE will establish valuable collaborative relationships with external labs and university teams.
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Patterns of Pathogenicity
Lynette Hirschman, Principal Investigator
Location(s): Washington and Bedford
Problem
New infectious diseases are constantly emerging and concern with bioengineered weapons looms large in defense and public health planning. The rapid elucidation of the mechanisms (virulence factors) by which these bacteria and viruses cause harm is key to an effective and rapid response.
Objectives
We will provide automated aids for the elucidation of virulence mechanisms, based on analysis of the genome of a pathogenic organism and high-throughput assays of host-pathogen interaction. Understanding the mechanisms of host pathogen interaction is key to developing effective treatments, vaccines, and decontamination procedures.
Activities
We will bring the relevant pathogen data sets (text sources, gene annotations, pathway annotations) in-house and apply pattern recognition, data mining, and computational biology techniques to identify features associated with possible virulence factors. We will develop interactive tools, working with publicly available microarray data sets, to identify pathways associated with virulence and to validate our findings.
Impact
This effort will provide new insights into the mechanisms of pathogenesis, while advancing MITRE's expertise in biology, bioinformatics, and biological threat reduction. An ability to characterize and understand biological threat agents will position MITRE to support key sponsors in the areas of biodefense and biosecurity.
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Synthetic Biology: Engineering at the Sub-Cellular Level
John Dileo, Principal Investigator
Location(s): Washington
Problem
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.
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