| 2004 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).
Biocomputation
Jordan Feidler, Principal Investigator
Location(s): Washington
Problems A large and expanding repertoire of available physiological, biochemical, and molecular approaches has resulted in dramatic growth in the biological sciences. These advances are inherently dual-use. Although they have lowered the barrier for use in asymmetric warfare or terrorist activities, they have also demonstrated vast potential as a source for new enabling technologies.
Objectives DARPA's BioComputation Program will develop a computational framework, BioSPICE, that facilitates the rapid construction of sophisticated simulations of intracellular processes. This system will enable researchers to rapidly explore the effects of a novel pathogen and to quickly identify possible intervention strategies. Another goal is to develop novel and useful computational architectures, sensor devices, and physical structures using biomolecules.
Activities MITRE has had an active role in evaluating the usability, functionality, and architecture of the BioSPICE software. In addition, MITRE provides technical support in program management: evaluating current progress and identifying new areas of research that have the potential to significantly impact the program. MITRE has also staged technology demonstrations for government sponsors from multiple agencies.
Impact MITRE has taken a leading role in guiding one of the key scientific efforts that seeks to develop new technology for defending against biological threats. MITRE's FFRDC role has been crucial for presenting the program manager with an unbiased perspective on contributed BioSPICE software. MITRE is also facilitating the transition of developed technology to other government agencies and industry.
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Biotechnology and Computational Biology
Jordan Feidler, Principal Investigator
Location(s): Washington
Problems Biological agents present a significant challenge to homeland security and defense of the warfighter in asymmetric environments. The difficulty in dealing with biological threats is compounded by the relatively low barriers to entry to produce novel pathogenic agents. Improved techniques and methods combined with basic-level training can be exploited to aid in the design of new pathogens with increased virulence. Objectives This work will speed response to a novel pathogenic agent using computational modeling techniques to quickly identify how a biological agent acts to disrupt normal cellular processes. Our technical approach entails a process of iterative refinement whereby modeling and experimentation drive each other to increase our understanding of a particular cellular pathway commonly perturbed by biological warfare agents: FAS-mediated cell-suicide. Activities Our initial focus is on creating a computational model of the FAS-mediated cell death pathway, which is disturbed by a number of biological warfare agents. We are working in collaboration with the Molecular Pathology Department at the Walter Reed Army Institute of Research, where we receive training on the experimental techniques that will be required to test the models. Impact Computational models will allow for rapid estimation of how pathogenic a novel agent may be, so that countermeasures can be mounted that are commensurate with the posed threat. They will also shorten the time required to develop a possible pharmacological or antibiotic treatment by allowing researchers to explore alternative hypotheses in simulation and prioritize experimental approaches.
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Information Sharing in Neuroscience
Kenneth Smith, Principal Investigator
Location(s): Washington
Problems The sharing of neuroimagery offers great benefits to science; however data owners sharing their data face significant custodial responsibilities, such as ensuring their data is correctly interpreted in its new shared context, protecting the identity and privacy of human research participants, and safeguarding the understood order of use. Given simple choices of sharing widely or not at all, the result will frequently be no sharing, due to the inability of data owners to control their exposure to the risks associated with data sharing. Objectives We hypothesize that neuroimagery sharing will be enhanced if data owners are provided with well-defined intermediate levels of data visibility. Two enablers are required: a model defining such levels, and tools implementing them. Activities We have defined a data sharing model, Structured Sharing Communities (SSC), in which a customized policy space is defined capturing the sharing relationships among specific collaborators. We present a set of three prototype data sharing tools that implement the SSC model and enable data sharing: the Policy Space Editor, the Data Labeler, and the Data Interface. Users express their query through pull down menus, radio buttons, etc.. The Interface tool filters the returned data appropriately according to the user's sharing affiliations. Impact Together, this community-based sharing model and associated suite of tools enable simple and intentional sharing of many types of data. This MITRE effort is currently being accepted and deployed within the neuroimagery research community. We are investigating the applicability of this model to traditional MITRE sponsors.
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Neuroinformatics
Monica Carley-Spencer, Principal Investigator
Location(s): Washington
Problems 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 lack 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 made significant progress toward development of a digital library, including schema integration, a data sharing policy space, and Web-based tools for exploring the data. The project focus is on medical image exploitation: designing query-by-example functionality, enhancing querying using data mining, and developing data quality metrics intrinsic to the neuroimagery. We are also continuing to acquire MRI data from our collaborators. 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 readily transition to our Treasury Department, DoD, and USGC sponsors.
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Neuroscience of Memory Workshop
Mark D. Happel, Principal Investigator
Location(s): Washington
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Pathogen Capture Using Floating Films
Elaine Mullen, Principal Investigator
Location(s): Washington
Problems 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 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 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 means of selectively concentrating pathogens at the surface of drinking water reservoirs. This technology may provide the basis of a 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
Problems New 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 microbes cause harm is key to an effective and rapid response. Objectives We propose to automate detection and classification of virulence factors based on analysis of the genome of a pathogenic organism. Biologists have identified classes of virulence factors; diverse pathogens share many of these virulence factors and often exchange "islands of pathogenicity." Using the genome to identify virulence factors is key to developing effective treatments, vaccines, and decontamination procedures. Activities We will bring the relevant pathogen data sets 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 Los Alamos National Laboratory. The LANL virulence factor database will be used to validate our detection and classification techniques. Impact This effort will provide new insights into the mechanisms of pathogenesis, while advancing MITRE's expertise in biology, bioinformatics, and biological threat reduction. We will partner with LANL to contribute to a key national database on virulence factors. This work will position us to play a major role in biodefense research, supporting key MITRE sponsors.
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Rapid Diagnosis of Biological Warfare Agent Exposure
Olivia Peters, Principal Investigator
Location(s): Washington
Problems It is difficult to determine if a biological attack has taken place because the technology does not exist for rapid and early diagnosis of 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 first year of the project will focus mainly on development of a database schema and feature extraction algorithms. The second year will mainly concentrate on similarity metrics, and in the final year we will design and implement the classifier. Impact The major impact will be to 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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