The COVID-19 pandemic, while demonstrating the nation’s vulnerabilities to biothreats, has also shown the fragility of the supply chain. The United States relies on foreign suppliers for a number of critical components including commodity chemicals, rare earth elements and active pharmaceutical ingredients, she said. Ensuring a resilient domestic supply chain for these components is a major priority for the Pentagon.
The need to develop new and more advanced biotech is identified as a modernization priority in the 2018 National Defense Strategy, which focuses on great power competition with advanced adversaries China and Russia. “One of the opportunities here for the Department of Defense is its potential to provide new sources of critical materials,” said Michelle Rozo, assistant director for biotechnology at the office of the undersecretary of defense for research and engineering.
Agencies throughout the Defense Department are investing in biotechnologies and working initiatives to harness nature’s processes to better support warfighters. Some biological systems are able to naturally produce materials that are difficult, expensive, or impossible to produce by traditional means.
DARPA wants to utilize the potential of Synthetic biology, to provide on-demand bio-production of novel drugs, new materials, food, fuels, sensors and coatings whatever suits the military’s needs. Future advances might include the construction of new biological parts and brain-computer interfaces. Potential defense applications include sensor active materials, high strength polymers for armor, stealth materials, corrosion-resistant coatings, biological computing; data storage, and cryptographic materials. Spider silk, for example, is stronger than steel, and abalone shells are tougher than glass and more flexible than plastic. More powerful fuels might also come from genetically engineered microbes, said former DARPA director Arti Prabhakar.
One initiative is the Defense Advanced Research Projects Agency’s Living Foundries program. The initiative seeks to transform biology into an engineering practice by developing the tool technologies, methodologies and infrastructure to prototype and scale engineered microbes that can produce molecules that are of value for government and commercial use, said Melissa Rhoads, advocate for biotechnology at Lockheed Martin, during the webinar.
Renee Wegrzyn, DARPA’s Living Foundries program manager, said the challenge for the Pentagon is that it lacks bio-manufacturing capabilities to generate molecules and materials that are cost-effective, domestically sourced and have high-performance rates for a broad range of applications. DARPA has an effort within the Living Foundries program called “1,000 molecules,” which is dedicated to manufacturing molecules domestically that are relevant to the military, cost effective and customizable for enhanced performance, she said.
The focus is on “understanding where do current materials and molecules fail, and [where] we can make them better, make them domestically, and … in an agile way,” Wegrzyn said. The program is exploring various manufacturing methods as it pursues the technology, she noted. Living Foundries is also aiming to improve the quality of biological medical countermeasures such as chemical weapon filtration capabilities. “Think of a garment that could bind and neutralize chemical weapons” much like a filter, Wegrzyn said. “We have solutions now, but we know that there’s a gap — that we can make those capabilities better.”
As it works to meet its goals, the 1,000 molecules program is first focusing on the design aspect of biotech. “Design here means finding what is the biosynthetic pathway — what are the genes that I need to layer on here and how can I design that very quickly,” she said. “We have multiple cases where we may in nature identify an enzyme that looks like it should do the trick, but we actually have to test 100 different variants before we find the one that really works the way that we want it to.” Next the scientists build and synthesize DNA to insert it into organisms in order to produce molecules. They then grow and test the organisms, which can be a time consuming task, she said.
“The dirty little secret here is that most of the time it doesn’t work and we actually have to iterate on those designs over and over,” Wegrzyn said. “We have made millions of different variants to learn those rules and apply them and enhance performance going forward so that we can scale this foundry output.”
DARPA hit the 1,000 molecules goal more than a year ago and has since manufactured more than 1,500 of them, Wegrzyn said. That has allowed the agency to “pivot our investing and say: ‘Well, now let’s actually start to make things and test them and see if they can perform better,’” she said. DARPA is working with the Air Force Research Laboratory, the Naval Air Warfare Center Weapons Division and various cohorts in the Army on testing and evaluation, she said. “This is really relevant to the whole military,” she said.
Meanwhile, the Army is working to produce materials using biotechnology through its Transformational Synthetic Biology for Military Environments Program, also known as TRANSFORME. “One of the things that we’re really looking to exploit for the Army is if we can harness these low-costs, low-energy routes of production of materials in a forward [operating] context,” said Dimitra Stratis-Cullum, the essential research program manager at the Army Research Laboratory. “Then we can really start to change the equation on logistics and sustainment.”
TRANSFORME is a dedicated effort bringing together synthetic biology, biotechnology, scientists and engineers in a focused way, she said. “What we’re doing is trying to build the agility to adapt and push into the rapid genotyping to rapid prototyping space,” Stratis-Cullum said. Researchers are looking to use biology to advance capabilities in the areas of coatings composites by improving corrosion resistance to protect military equipment, she noted.
One of the most wondrous aspects of life is that all living organisms are formed through self-assembly, a fundamental biological design process by which an organized structure seemingly builds itself from a disordered collection of smaller parts. On a large scale, self-organizing behavior’s powerful effects are seen when small gusts of wind join together to form a tornado that can wreak havoc on infrastructure and natural resources in its path, writes Wyss Institute. And on a much smaller scale, this same principle is seen when two strands of DNA zip up to form the double helix that encodes our genome. Or, when cells self assembles into embryonic tissues that further develop into fully formed humans and animals.
Self Assembly is also a design principle that Wyss Institute faculty and staff leverage in their research to create new materials and devices with unique behaviors and properties. Wyss Institute scientists have developed injectable nanoparticles that aggregate at sites of disease or injury inside the body, where they can recruit immune system factors or circulating drugs to treat illness or attract stem cells to regenerate tissues.
DNA Origami is being used to create new nanoscale drug delivery systems and immune adjuvants. Implantable biomaterials are being fabricated that induce living cells to self organize to form functional tissues and organs. And other Wyss researchers are designing collective swarms of robots small enough to traverse tiny spaces within collapsed buildings, where they could then self assemble into larger collectives with enough force to open passageways for inspection or escape.
Self-assembly-based manufacturing refers to a controlled process of using self-assembly and programmable matter to manufacture a product on an industrial scale. In traditional manufacturing and fabrication, there are physical and precision limitations on a workpiece; namely, lower minimal dimension of a workpiece has been a major challenge in modern manufacturing. Engineering self-assembly methods have a significant potentials in overcoming the dimensional limitation of a workpiece.
In general, there are three key ingredients in most of self assembly applications: geometry (order), interaction, energy. To improve the efficiency or take shape in self-assembly based manufacturing, it must utilize one or more than one of these three ingredients. This is an emerging market with few examples to date. However, this field shows a strong potential to revolutionize many industrial markets from nanoelectronics to bio-engineering.
Fabrication of materials used in most extreme environments, such as space, high altitude, free-fall scenarios, or deep sea environments have advantageous conditions for allowing increase in self assembly interaction with less or minimum energy consumption. Applications in these environments often require high precision and have more difficulties; however, it has fewer constraints in existing construction.
A New Way to Build Novel Synthetic Biomolecules: ARL & University of Texas at Austin’s
Army scientists have disovered how to build novel synthetic biomolecule complexes that they believe are a critical step towards biotemplated advanced materials. Their work was featured in the March 2019 issue of Nature Chemistry.
A team of researchers from the U.S. Army Combat Capabilities Development Command’s Army Research Laboratory, the Army’s corporate research laboratory also known as ARL, and The University of Texas at Austin’s Department of Molecular Biosciences, combined pairs of oppositely charged synthetic proteins to form hierarchical ordered, symmetrical structures through a strategy they termed as “supercharged protein assembly.”
Dr. Jimmy Gollihar, a synthetic biology research scientist at ARL, along with University of Texas at Austin professors, Drs. Andrew Ellington and David W. Taylor, Jr., collaborated on this discovery.
The researchers said synthetic protein units had their surface charge artificially augmented to create either a positively or negatively charged protein unit to create supercharged proteins. This feature allowed the team to create self-assembled structures that are driven by charge alone.As a demonstration of this capability, the team used computational modeling to design two fluorescent proteins, one super positive and the other super negative.
Gollihar explained that when the team synthesized and mixed the oppositely supercharged fluorescent proteins, it resulted in well-ordered aggregates. “Our simple charged proteins assembled into well-ordered structures in a manner that has not been observed in nature,” Gollihar said. “These protomers are aggregates of two oppositely charged pairs of fluorescent proteins. Once the protomers form, they can be reversibly assembled by altering the ionic strength or pH of the solution. At very low ionic strength, the proteins assemble into structures that are larger than bacterial cells.”
Gollihar indicated this begins to address questions on how protein structures can be engineered into templates for advanced materials. “Biology is exceptional at Angstrom-level scales that current manufacturing methods cannot access,” he said. “By studying the self-assembly and functionalization at this level, it should prove possible to manufacture nanoscale materials for a host of Army-relevant applications.
He said synthetic biology is a key technology area that has disruptive potential to shape how the Army will fight and win in the future operational environment. “These efforts will be followed by attempts to engineer protein structures with unique properties suitable for Army applications such as bio-enabled sensing and functional coatings,” Gollihar said. “The ready assembly of this structure suggests that combining oppositely supercharged pairs of protein variants may provide broad opportunities for generating novel architectures via otherwise unprogrammed interactions.”
This foundational work will continue, expanding in scale and composition, as part of Transformational Synthetic biology for Military Environments, or TRANSFORME, one of ARL’s essential research programs. “TRANSFORME is about programmable control of biological processes allowing not only expeditionary capabilities in multi-domain operation, but also adaptation at operational tempo, a pace that can define a country’s dominance in battle,” said Dr. Dimitra Stratis-Cullum, program manager for TRANSFORME.
New Army-funded synthetic biology research manipulated micro-compartments in cells, reported in April 2021
New Army-funded synthetic biology research manipulated micro-compartments in cells, potentially enabling bio-manufacturing advances for medicine, protective equipment and engineering applications. Bad bacteria can survive in extremely hostile environments — including inside the highly acidic human stomach—thanks to their ability to sequester toxins into tiny compartments.
In a new study, published in ACS Central Science, Northwestern University researchers controlled protein assembly and built these micro-compartments into different shapes and sizes, including long tubes and polyhedrons. Because this work illuminates how biological units, such as viruses and organelles, develop, it also could inform new ways to design medicine, synthetic cells and nano-reactors that are essential for nanotechnology.
“These results are an exciting step forward in our ability to design complex protein-based compartments,” said Dr. Stephanie McElhinny, program manager at the U.S. Army Combat Capabilities Development Command, known as DEVCOM, Army Research Laboratory. “Being able to control the size and shape of these compartments could enable sophisticated bio-manufacturing schemes that are customized to support efficient production of complex molecules and multi-functional materials that could provide the future Army with enhanced uniforms, protective equipment and environmental sensors.”
Further down the road, these insights potentially could lead to new antibiotics that target micro-compartments of pathogens while sparing good bacteria. Researchers control protein assembly and build cell micro-compartments into different shapes and sizes that could lead to bio-inspired building blocks for various engineering applications. “By carefully designing proteins to have specific mutations, we were able to control assembly of the proteins that form bacterial micro-compartments,” said Dr. Monica Olvera de la Cruz, professor of materials science and engineering and chemistry at Northwestern who led the theoretical computation. “We used this also to predict other possible formations that have not yet been observed in nature.” Many cells use compartmentalization to ensure that various biochemical processes can occur simultaneously without interfering with one another. Made of proteins, these micro-compartments are a key to survival for a wide variety of bacterial species.
“Where we’re pushing the boundaries right now is really the structure function property relationships, and the ability to do this will go beyond coatings,” she said. However, even in “areas such as stability of composites for propellants for long-range munition fires or many other aspects, once we start to tackle this space we can use these tools to more broadly impact design and production.” Meanwhile, the Air Force Research Laboratory’s manufacturing directorate is working quickly to address an issue brought on by the COVID-19 pandemic. The directorate is one of nine under the umbrella of AFRL and it focuses broadly on material science, manufacturing technology and system support for materials once deployed, said Maneesh Gupta, a materials engineer at the directorate.
One research thrust is looking at how to eliminate microbial contamination in a way that is compatible with the materials that are found onboard aircraft, he said. “Over the last three or four months — as the pandemic has sort of kicked up into high gear — there has been a really important need for the DoD to figure out how they can decontaminate aircraft that had been moving personnel around that might’ve been potentially contaminated with the virus,” he said. The directorate is examining appropriate solutions that will not degrade or hurt the materials that are onboard an aircraft, but will still safely eliminate the pathogen, he noted. “The team has really been very quickly responding to that situation and providing some really critical answers,” he said.
The Office of Naval Research is also looking toward natural systems to support its mission. The organization is working to identify and exploit key principles and organisms from nature and use them as the basis to design and control materials, sensors and devices, said Linda Chrisey, program officer for ONR’s synthetic biology for naval applications. It also wants to use the technology to provide new power strategies for the service. The service’s biocentric technology program is aiming to provide greater capabilities for powering platforms in a variety of environments, she said. “We do think about undersea powering — the seafloor is becoming an important domain for us,” she said. “We have sensors and communication devices that would like to power for a long time and, of course, accessing those sites can be logistically challenging for many reasons.”
The survivability of platforms in austere environments is also a concern that the office is trying to address. ONR has focused on creating biologically inspired autonomous vehicles where it examines how marine and amphibious animals both move and navigate. “Then [we] extract those principles to develop novel autonomous vehicles both from the platform itself, as well as the control algorithms that allow those vehicles to maneuver and operate in those environments,” she explained. Overall, the Pentagon is investing in capabilities and initiatives that it believes across the board have the potential to reduce the threat to warfighters and increase mission readiness, Rozo said.
The Defense Department is imagining future scenarios and “projecting outwards to what biotechnology can provide, where we’ve mastered the discipline and the ability to do point-of-need production so that these same necessary items — these fuels, these lubricants, this food — can be produced at the point where the warfighters need it and relevant quantities and in mission relevant time frames,” she said.
US ARL and Lockheed Martin partner on bioproduction of new materials
In 2019, The US Army Research Laboratory (ARL) and Lockheed Martin entered a new cooperative agreement to incorporate the bioproduction of new materials. Named Self-Assembly of Nanostructures for Tunable Materials, the $10m, five-year agreement aims to study a range of capabilities, especially ones that can enhance defence optical technology and coatings.
The bioproduction agreement will use the Army’s Open Campus model to bring together university, small-business, Army and Lockheed Martin scientists and engineers. US ARL research chemist and essential research programme manager Dr Dimitra Stratis-Cullum said: “The collaborative effort with Lockheed Martin came about from conversations, reviews and workshops revolving around our strategic growth and collective interest in this area to ultimately make a game-changing impact on the army and the soldier.”
“ARL is providing the synthetic biology expertise, facilities needed to gain an understanding of biological assembly through combined efforts in genetic control, material-based screening and modelling. Lockheed Martin is bringing design and experience in manufacturing and systems expertise through interdisciplinary scientists across their many business units.”
Lockheed Martin is currently exploring the creation of building blocks of novel materials. It will work with industry and army scientists to reprogramme single-cell organism deoxyribonucleic acid (DNA) as part of the agreement. “Biodesign exists today, but it doesn’t exist at the scale and to the quality of defence standards.” Lockheed Martin project lead and senior research manager Melissa Rhoads said: “Cells efficiently create all sorts of materials, like a spider’s silk or a butterfly’s iridescent wings. We want to harness nature’s process to better protect people. Biodesign exists today, but it doesn’t exist at the scale and to the quality of defence standards.”
The collaboration will also see the use of commercial developments from companies, such as Ginkgo Bioworks. It will also assess bio-produced magnetic molecules including various other particles for use in optical technology enhancements. “We can’t manufacture that kind of capability, so Lockheed Martin will try nature’s way,” Rhoads added.
“Harnessing the power of self-assembling materials is sustainable, affordable and can be much faster to produce than artificial methods. As much potential there is for bio-design, the maturity of the materials technology is still low, so our five-year study will advance this field significantly for precision science.”
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