Results for “Biosciences” — Page 5

DOE OSTI2024

Novel microbial based enzymatic CO2 fixation mechanisms: Conformational control of enzymatic reactivity

The broad, long-term goal of the research is to provide insight into the mechanism of novel carboxylation and electron bifurcation reactions as paradigms to study how enzyme utilized protein conformational change to protect reactive intermediates and/or control the pathway in a catalytic cycle. catalyzed by enzymes involved in bacterial alkene, ketone, and epoxide metabolism. We are examining two paradigms in which conformational change is a key mechanistic feature of 1) protecting reaction intermediates that are sensitive to breakdown in the presence of water and 2) directing electron flow in reactions that split electron pairs along two pathways in reactions that fine tune metabolic efficiency in microbial metabolism. Both paradigms are of key importance in defining the molecular determinants of reactions relevant to CO 2 capture and fuel upcycling. In the first paradigm the compounds acetone and bicarbonate are activated by the addition of phosphate creating reaction intermediates (phosphoenolacetone and carboxyphosphate) that are very sensitive to breakdown in the presence of water. We are studying the mechanism of how the enzyme protects these reactive intermediates from water by encapsulating them upon their formation within a hydrophobic protein channel leading to an enzyme active site approximately 40 Å away. In the second paradigm, we are examining how the direction of electron transfer reactions can be modulated through protein conformational change that alters either the difference driving force or distance or both between electron transfer pathways in enzymes that catalyze electron bifurcation. We are using a combination of enzyme kinetics, mass spectrometry, spectroscopy, and structural analysis through X-ray diffraction and scattering methods to characterize the mechanism of conformational changes along the catalytic path. Within the context of the mission of the Department of Energy and the core activities of the Energy Biosciences, the results obtained in the study will reveal new insights into the fundamentals of novel carboxylation / CO 2 capture chemical transformations and electron transfer reactions that equate to biological fuel upcycling.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

The Scientific Case for Concurrent Neutron and X-ray Scattering and Spectroscopy

The interrogation of materials with X-rays or neutrons to determine the structure, energetics, and dynamics of materials is fundamental to advancing materials' physical and chemical science and developing innovative material technologies. A transcending challenge in developing novel materials is that progress hinges on understanding the structure and dynamics across multiple time and length scales in complex materials that feature multiple components, interfaces, and compositions. Despite the ever-growing demands on materials’ characterization, existing approaches are almost exclusively based on isolated X-ray or neutron scattering, i.e., an approach commensurate with the more narrowly defined needs of fifty years ago. A three-day workshop sponsored by the U.S. National Science Foundation (NSF) analyzed the demand for concurrent neutron and X-ray (NeX) experiments. It was held at the Spring Hill Suites, San Jose, California, from June 2 to 4, 2022. In this workshop, 70 national and international experts ascertained the crucial need to establish NeX capabilities to advance the science of complex materials and systems in the US. Here, we illustrate the need for NeX scattering and spectroscopy experiments by showcasing examples that span areas as diverse as biomaterials, energy science, soft matter, and nanomaterials. To provide NeX capability will require new instrumentation that enables concurrent experiments. Affected areas include chemistry, soft matter, quantum materials, pure and applied chemistry, bioscience, geoscience, and applied materials. NeX benefits research outcomes due to the complementarity of the two techniques, which is essential for better model refinement. While joint refinement of data from separate neutron and X-ray experiments is critical to avoid ambiguities, especially in multiphase-multicomponent materials, concurrent experiments overcome scientific and technical barriers associated with single measurements, separated by location and, thus, time. Among all the examples, these factors introduce uncertainties in the results that complicate data analysis. [1,2] [3] While models are strongly sample-dependent, the principles of joint refinement are generally applicable to these disciplines, including the development of advanced parameterization, modeling, and analysis techniques that also consider the temporal and spatial resolutions of the two methods, leading to unambiguous data interpretation. Solutions for technical barriers must be found to realize NeX experiments, including developing robust sample environments that meet the optical requirements of neutrons and X-rays.

36 MATERIALS SCIENCE↗

DOE OSTI2023

Optimization of Spirulina for biomanufacturing and the delivery of protein therapeutics

Lumen Bioscience has developed a novel cyanobacterial platform that enormously decreases the cost of pharmaceuticals used to prevent and treat illnesses. Arthrospira platensis (spirulina), is a photosynthetic microorganism that has been consumed as a dietary supplement for centuries in part because of its high protein content. Commercial cultivation operations have matured over the last 50 years to allow large-scale cultivation in outdoor ponds. Lumen recently discovered methods that transform this commercially important cyanobacterium into a genetically tractable platform for bioengineering. The high protein accumulation in spirulina makes it an ideal chassis for heterologous protein expression, and centuries of safe human consumption suggest its utility as an administration vehicle for biologic drugs. Lumen can express a broad range of recombinant proteins in spirulina and has developed manufacturing processes and strains to mucosally deliver bioactive proteins to treat and/or prevent disease. For example, Lumen has produced an oral cocktail of dried whole-cell spirulina biomass, containing 3 toxin-neutralizing antibodies and 1 endolysin, that is efficacious in a preclinical in vivo models of C. difficile infection. Lumen has also demonstrated that intranasal administration of a spirulina-manufactured neutralizing antibody can prevent disease by a respiratory pathogen, SARS-CoV-2, in a hamster model. Lumen’s current pipeline includes therapeutics to treat or prevent C. difficile infection, COVID-19, inflammatory bowel disease, cardiometabolic disease, and traveler’s diarrhea. Lumen deploys strategies to maximize the expression of these therapeutics for optimal dose sizing, a key limiting factor with past food crop-based expression systems. Spirulina can express exogenous proteins at unusually high levels (>15% of dry weight) but reaching this maximum value requires optimization of multiple interacting factors. We describe our current statistics design of experiments approach that optimizes these factors with minimal replicates. This maximizes exogenous protein expression allowing Lumen to generate spirulina-based therapeutics for a rapidly expanding range of medical uses.

Heinnickel, Mark↗

DOE OSTI2024

National User Resource for Biological Accelerator Mass Spectrometry

The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide isotopic analysis (primarily radiocarbon or 14C) by accelerator mass spectrometry (AMS) for NIH- funded researchers across the United States and will be the only User Resource of its type in the United States. The User Resource will provide measurement capability and expertise to a research community that requires highly sensitive, quantitative isotope analyses. Since commissioning a new accelerator mass spectrometer in June 2014, we have measured over 4000 samples a year for collaborators and service users. The User Resource will enable us to continue to meet these research needs, as well as provide for new users whose research programs would benefit from AMS as a measurement tool. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies have been and will continue to be an important tool for addressing many complex biomedical science problems. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and other relevant radioisotopes with extreme sensitivity, having limits of detection in real samples on the order of a few attomol/mg of sample at measurement precisions of ~3%. It is the only instrumental method capable of quantifying radioisotope-labeled agents routinely in real-world samples with such precision and sensitivity. The sensitivity of AMS allows for the quantification of radiolabeled metabolites in extremely complex matrices of cells and organisms at very low concentrations and in small samples. AMS allows studies to be conducted without perturbing metabolism leading to more relevant quantification of metabolic rates and pathways. In addition, it enables quantification of pharmacokinetic and metabolic properties of toxicants at environmentally relevant concentrations in model systems as well as the ability to quantify pharmacokinetics and other molecular endpoints directly in humans. Such quantitative assessments can 1) improve risk assessment for toxicants, 2) address safety and efficacy considerations for therapeutic entities, 3) deepen understanding of xenobiotic and intermediary metabolism, 4) help understand the interactions between critical molecular pathways, and 5) improve efforts to model and predict various metabolic and biological states. These capabilities have been applied in a number of areas including research in carcinogenesis, toxicology, nutrition, pharmacology/drug development and basic biological science. As a NIGMS National Resource the National User Resource for Biological Accelerator Mass Spectrometry will help NIH funded scientists achieve a deeper understanding of the etiology of human health concerns by (1) enabling the quantification of pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids, and thereby reducing the amount of radioisotope usage in biomedical labs; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles and enable research supported by the Biophysics, Biomedical Technology, and Computational Biosciences (BBCB); Genetics and Molecular, Cellular, and Developmental Biology (GMCDB); Pharmacology, Physiology, Biological Chemistry (PPBC) and Training, Workforce Development, and Diversity (TWD) Divisions.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2024

Energetics and Kinetics of Syntrophic Aromatic Degradation (Final Technical Report)

This DOE Basic Energy Physical Biosciences project spanned a 28-year period and two project investigators. Numerous significant research discoveries have occurred over this time frame. Much of this work has been reported in peer-reviewed literature, with the publication of results from the last four years forthcoming. The overarching project themes have focused on probing the metabolism of syntrophic bacteria and their environments. Research supported by this project has been central to ten doctoral dissertations and one master’s thesis at the University of Oklahoma. The project has also supported numerous undergraduate research projects throughout the years. Additionally, several microbial genomes were sequenced and annotated in association with this work 12-16. Key findings and publications from this work are highlighted. More detailed results are provided for unpublished and embargoed work. A complete list of publications and research products associated with this project is at the report's end.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Science & Technology Review September 2024

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

24 POWER TRANSMISSION AND DISTRIBUTION↗

DOE OSTI2024

Science & Technology Review: October-November 2024 DarkStar

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2024

S&TR December 2024 El Capitan issue

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2024

S&TR Jan-Feb 2024 (Wind Tunnel - EMIT Issue)

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2024

S&TR April/May 2024 EMDEC Issue

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation's security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory's scientific and technological accomplishments in fulfilling its primary missions. The publication's goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2025

S&TR Jan/Feb 2025 Partnerships Issue

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2024

Research Reactors Division Infrastructure Investment Plan for the High Flux Isotope Reactor

The High Flux Isotope Reactor (HFIR) is a unique national asset. Operational for nearly 60 years, continued investment into the aging infrastructure is necessary to ensure operation for another 6 decades. Additionally, growing missions require HFIR as well as important upgrades. Consequently, carefully integrated planning is required to ensure that infrastructure investments are timely executed to ensure long-term, reliable operation of HFIR. Concerns about challenges to the operational reliability of HFIR resulted in a recommendation from the 2023 Operations Review by the US Department of Energy (DOE) Office of Basic Energy Sciences that a HFIR management strategy be developed to address the infrastructure needs. This report defines the investment needs, which are evolving as new upgrade efforts are better defined. HFIR is part of the three-source strategy within the Neutron Sciences Directorate (NScD) and contributes to the five strategic science areas outlined in the NScD 10 Year Strategic Science Plan: quantum materials, soft matter, materials and engineering, chemistry, and biosciences. Fundamental to this strategy are three core values: operational excellence, responsible stewardship, and servant leadership. These values guide our mission of safe and reliable operation of the reactor and require a strong and just nuclear safety culture, a solemn respect for responsible care of the facility, good workforce development, robust procedures and processes, an effective communication strategy, world-class asset management, a determined customer focus, and a commitment to protecting the environment, the safety and health of the public and our people, and the quality of work performed within our facility. These principles are all essential to operate HFIR at a world-class level. The Research Reactors Division (RRD) will lead a new era of neutron science and isotope production at HFIR through responsible and purposeful leadership and unwavering support of the science community. The approach outlined in this plan highlights the direction leadership is taking to ensure that HFIR is ready to support the science challenges and national needs of the future and that the United States maintains world leadership in neutron sciences. The plan is in alignment with the DOE’s desire to continue operating HFIR and with the NScD strategic science goals for the future. HFIR is an aging facility with numerous infrastructure challenges and needs. It has an aging workforce in relation to the general population of Oak Ridge National Laboratory (ORNL), with many expected retirements over the next 5–10 years. With an increase in work scope caused by changing national priorities and science goals, several critical hires have been identified. To manage HFIR’s infrastructure needs, a prioritized list of equipment upgrades has been identified along with an analysis of future staffing requirements. A desire to operate HFIR at eight cycles per year will necessarily require some significant changes to procedures and processes currently in place as well as targeted staffing additions. Many of the equipment upgrades identified in this plan will significantly increase the reliability of the plant, thus contributing to the effort to reach the goal of safely operating eight cycles per year. A plan to attain eight-cycle operation is being prepared in parallel with the activities identified in this plan, although the actions identified to satisfy both plans will overlap. This plan identifies new infrastructure needs—for both plant equipment and staffing—thus necessitating formulation of future budget requests to fund the increased work scope and improvement activities. Some activities are currently being scheduled with the expectation that funding will be received. Any delays to funding or reductions of funding from the identified cost estimations will directly and negatively affect the plan’s implementation.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

DOE OSTI2025

S&TR April/May 2025 Power Grid

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2025

S&TR June 2025 R&D 100 Awards

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2025

National User Resource for Biological Accelerator Mass Spectrometry (Final Report)

The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide isotopic analysis (primarily radiocarbon or 14C) by accelerator mass spectrometry (AMS) for NIH- funded researchers across the United States and will be the only User Resource of its type in the United States. The User Resource will provide measurement capability and expertise to a research community that requires highly sensitive, quantitative isotope analyses. Since commissioning a new accelerator mass spectrometer in June 2014, we have measured over 4000 samples a year for collaborators and service users. The User Resource will enable us to continue to meet these research needs, as well as provide for new users whose research programs would benefit from AMS as a measurement tool. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies have been and will continue to be an important tool for addressing many complex biomedical science problems. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and other relevant radioisotopes with extreme sensitivity, having limits of detection in real samples on the order of a few attomol/mg of sample at measurement precisions of ~3%. It is the only instrumental method capable of quantifying radioisotope-labeled agents routinely in real-world samples with such precision and sensitivity. The sensitivity of AMS allows for the quantification of radiolabeled metabolites in extremely complex matrices of cells and organisms at very low concentrations and in small samples. AMS allows studies to be conducted without perturbing metabolism leading to more relevant quantification of metabolic rates and pathways. In addition, it enables quantification of pharmacokinetic and metabolic properties of toxicants at environmentally relevant concentrations in model systems as well as the ability to quantify pharmacokinetics and other molecular endpoints directly in humans. Such quantitative assessments can 1) improve risk assessment for toxicants, 2) address safety and efficacy considerations for therapeutic entities, 3) deepen understanding of xenobiotic and intermediary metabolism, 4) help understand the interactions between critical molecular pathways, and 5) improve efforts to model and predict various metabolic and biological states. These capabilities have been applied in a number of areas including research in carcinogenesis, toxicology, nutrition, pharmacology/drug development and basic biological science. As a NIGMS National Resource the National User Resource for Biological Accelerator Mass Spectrometry will help NIH funded scientists achieve a deeper understanding of the etiology of human health concerns by (1) enabling the quantification of pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids, and thereby reducing the amount of radioisotope usage in biomedical labs; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles and enable research supported by the Biophysics, Biomedical Technology, and Computational Biosciences (BBCB); Genetics and Molecular, Cellular, and Developmental Biology (GMCDB); Pharmacology, Physiology, Biological Chemistry (PPBC) and Training, Workforce Development, and Diversity (TWD) Divisions. Over the next five years, our goals are to: 1. Improve the efficiency of operation for AMS measurements through installation of new interfaces to our AMS systems, technical modifications to improve gas accepting ion source efficiency and upgrading our data analysis software for improved ease of use and data reporting. 2. Increase the accessibility and visibility of ultra-sensitive 14C measurements for the biomedical research community by training of new investigators and expanding our national user base. 3. Provide high throughput, ultra-sensitive 14C analysis for the NIGMS and NIH user community.

47 OTHER INSTRUMENTATION↗

DOE OSTI2025

Science & Technology Review December 2025 - Optimizing Future Design

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

36 MATERIALS SCIENCE↗

DOE OSTI2026

TCF Base Technology-Specific Final Report: Engineering Enzymes for Crystalline PET Substrate

The primary objective of this project was to develop a new polyethylene terephthalate (PET) hydrolase enzyme to depolymerize relevant PET substrates for Birch Biosciences, using high-throughput protein expression, purification, and assaying systems and machine learning-guided enzyme design. As a secondary project objective, we also aimed to develop a more energy-efficient ethylene glycol (EG) recovery strategy relative to distillation.

09 BIOMASS FUELS↗

DOE OSTI2026

Science & Technology Review: March 2026 - The Future of Lasers

At Lawrence Livermore National Laboratory, we focus on science and technology research to ensure our nation’s security. We also apply that expertise to solve other important national problems in energy, bioscience, and the environment. Science & Technology Review is published eight times a year to communicate, to a broad audience, the Laboratory’s scientific and technological accomplishments in fulfilling its primary missions. The publication’s goal is to help readers understand these accomplishments and appreciate their value to the individual citizen, the nation, and the world.

36 MATERIALS SCIENCE↗