Biosciences and biotechnology represent a major area of focus at Sandia/California. Our efforts span a broad spectrum of research and development, including fundamental research in understanding biological phenomena and applied R&D for developing point-of-care medical diagnostic devices. The two major thrusts in the area of biology are biodefense and bioenergy; however, we also have projects in other areas such as bioremediation. To support these thrusts, we have developed a number of capabilities, including biological mass spectrometry, molecular and cell biology, protein engineering, computational biology, and microfluidics.
To protect our nation from biological attacks, Sandia researchers are studying the interaction of immune cells with pathogens at single-cell resolution. Left: A macrophage in late-stage infection with the bacterium Franciscella novicida. Right: A microchip used to study cell signaling in macrophages infected with bacteria. (Source: Todd Lane and Julia Kaiser)
Biodefense research plays an important role in Sandia’s national-security mission. We have a highly interdisciplinary research staff — including biologists, chemists, engineers, and computational biologists — engaged in both basic and applied research in biosciences and biotechnology. Our goal is to address problems with strong ties to national security by developing advanced technologies and new research approaches.
Our efforts range from basic research investigating host–pathogen interactions and virulence mechanisms in pathogens to applied research that is developing point-of-care clinical diagnostic devices, portable detectors for biological agents, high-throughput screening techniques for therapeutic targets, and proteomic platforms for biomarker discovery and validation. Sandia’s strong programs in biomaterials design, protein structure/function determination, proteomics, computational chemistry, computational biology, and microfluidics are working together to develop next-generation tools and materials for biodefense. Moreover, we have established state-of-the-art facilities in mass spectrometry, micro- and nanotechnologies, molecular biology, and biochemistry to perform research and development. Sandia’s biodefense research has been funded by the Laboratory Directed Research & Development program, as well as by external sponsors such as the National Institutes of Health, the Department of Defense, the Department of Homeland Security, and commercial entities.
The following Sandia biosciences and biotechnology projects are funded in the area of biodefense:
Sandia optical tweezer designer Thomas Perroud helps biologist Meiye Wu sort macrophage cells in microfluidic devices that use MISL technology. See news release…
As part of a multi-institutional and multidisciplinary effort, Sandia scientists are developing novel microfluidic and imaging tools and computational models to elucidate the molecular mechanisms of innate immunity with unprecedented speed, resolution, and throughput. This project involves researchers in both the California and New Mexico laboratories and at two academic partners, the University of Texas Medical Branch and the University of California at San Francisco.
Our overarching goal is to develop technologies to understand how immune cells respond to pathogens, such as bacteria and viruses, in the first few minutes and hours after exposure. We are especially interested in the molecular mechanisms used by pathogens to subvert an organism’s innate immunity and thus cause greater harm.
To achieve this goal, we are developing an integrated, high-throughput experimental and computational approach that provides “system-level,” quantitative, spatio-temporal data at single-cell resolution for an innate-immunity pathway — specifically, the toll-like receptor (TLR) signaling pathway. Our miniaturized measurement and analysis system will detect protein concentrations, states, and interactions in both individual host cells and a population of such cells. We will validate this system by integrating biological experimentation, microengineered platforms, imaging tools, and predictive models to quantify the response of the TLR signaling pathway in macrophages and epithelial cells that have been challenged with lipopolysaccharide and bacteria.
For more information, please download our MISL fact sheet, and read our news release.
Sandia researchers have developed a portable device that detects disease markers by analyzing saliva. Unlike blood, saliva can be collected noninvasively, rapidly, and inexpensively in both clinical and nonclinical settings. Hence, saliva may be the preferred bodily fluid in many applications. The increased interest in saliva diagnostics has also been spurred by rapidly accumulating evidence showing a correlation between analyte levels in saliva and serum.
The technology that underpins Sandia’s point-of-care diagnostic device can also be used to measure protein markers in other body fluids. This technology provides the following benefits:
Our integrated lab-on-a-chip tool uses high-specificity, electrokinetic immunoassays. Although the tool was developed and benchmarked for an enzyme implicated in periodontal disease, the device has a broad range of applications, including monitoring general inflammation markers in human serum; examining livestock in their pens for illnesses (e.g., foot-and-mouth disease); and detecting pathogens in saliva, serum, or nasal mucus.
For more information, please download our oral diagnostics fact sheet, or visit our project’s website.
Sandia biochemist Dan Throckmorton prepares to add a sample to a prototype microfluidic device that will detect biotoxin exposure in humans with speed and high sensitivity. See news release…
We are developing a portable device that can quickly screen individuals who may have been exposed to biological toxins. The device will perform rapid microfluidic-chip-based immunoassays (<3–10 minutes) with low sample volume requirements (10 μL) and appreciable sensitivity (nM–fM). Our microfluidic method facilitates hands-free analysis by integrating sample pretreatment (filtering, enrichment, mixing) with electrophoretic immunoassays to quickly measure analyte concentrations in minimally pretreated bodily fluids. The microfluidic chip will be integrated with miniaturized electronics, optical elements such as diode lasers, fluid-handling components, data acquisition software, and a user interface to create a portable, self-contained device. The proposed system will be easy to use, automated, and self-contained. In addition, the device will have a small footprint so that it can be used in point-of-care and point-of-incident settings.
For more information, please read our news release.
Sandia is partnering with other institutions to conduct cutting-edge, detailed analyses of specific proteins that could be used in a bioterror attack and of the small molecules that bind to these proteins. The goal is to create reagents that both improve the quality and decrease the costs of detecting select bioterror agents through affinity assays.
We’re developing a high-throughput computational process—dubbed the Protein Pipeline—for conducting this work. The Protein Pipeline will consist of the following steps:
To date, we have completely identified unique sites for some threat agents and have identified protein targets for others.
Sandia researchers are developing mass-spectrometry-based techniques to determine the 3-D structure of membrane proteins.
To advance knowledge about membrane proteins, Sandia funded groundbreaking research through its Interfacial Bioscience Grand Challenge project.
In particular, the team studied “signaling and intoxication” mechanisms that may enable biological agents, such as anthrax or botulism, to kill cells or interfere with the body’s internal signaling-systems agents. This knowledge is needed to develop new methods for detecting biological agents and to create drugs that will block bioagents.
To do this, the team developed unique experimental and computational capabilities for understanding the structure of membrane proteins. These capabilities include the following:
Gel electrophoresis showing the soluble proteins in D. vulgaris, a sulfate-reducing microbe. (Source: Rajat Sapra)
The U.S. Department of Energy (DOE) owns many sites that are contaminated with toxic metals and radionuclides. Leakage from nuclear reactors and storage areas has entered the groundwater, and in many cases, these plumes are gradually moving off-site towards residential areas or rivers. The cost to clean up these sites could reach several billions of dollars and could take many decades. However, a far cheaper solution may exist in either active bioremediation or natural attenuation by microbes. To explore this possibility, Sandia biochemists and engineers are part of a multi-institution collaboration that is investigating the use of bacteria to bioremediate uranium and other heavy metals.
The following project is funded in the area of bioremediation:
We are developing methods to identify proteins and protein complexes in microbial cells such as Desulfovibrio vulgaris, a sulfate-reducing microbe. This work is part of a DOE-funded project that is led by Lawrence Berkeley National Laboratory. Efforts are currently underway to understand the regulatory networks in anaerobic bacteria when subjected to a variety of stress conditions, including heat, extreme pH levels, and oxygen. To this end, we are applying a combination of transcriptomics, proteomics, and bioinformatics approaches so that we can identify the genes, synthesized proteins, and protein complexes involved in stress response pathways.
We are also using our microfluidic technology to investigate methods for performing genetic and proteomic analyses at the single-cell level. Such methods are particularly useful for analyzing bacteria that have been isolated from environmental samples and that cannot be easily cultured.
For more information, contact Anup Singh at (925) 294-1260.