The UCLA-DOE Institute is an Organized Research Unit of the University of California, Los Angles, descended from an AEC Laboratory established at UCLA in 1947 to further the mission of the Department of Energy, particularly in the health and environmental sciences. The Institute currently operates under a Cooperative Agreement between the Department of Energy and UCLA. The current term of the agreement runs from 2014 – 2019.
The goals of the Institute are determined by DOE staff and the Director and Principal Investigators with advice from the External Advisory Committee. Within UCLA, the Director reports to the Vice Chancellor of Health Sciences (reflecting the health-related history of the Institute) and the Vice Chancellor for Research. From time to time the Institute has sponsored various outreach programs. In the current period one of these programs is Global Mentoring (building centers of excellence abroad to collaborate with and mentor young scientists in various fields related to energy and materials research).
By agreement with DOE, research in the current period emphasizes discovery in the areas of bioenergy and biodesign, carbon capture, microbial genomics, and structural and functional studies of organisms and their constituents of interest to DOE. Also emphasized is the development of technologies that advance such studies. Research efforts are organized into two Divisions: (1) Microbial Genomics and Proteomics and (2) Systems Biology and Design.
Funding from DOE supports the research efforts of 12 Principal Investigators and 6 Core Technology Centers, as well as a lean Administrative Core. Reflecting the interdisciplinary nature of energy research, the PIs are drawn from 6 departments within the Schools of Letters and Science, Medicine, and Engineering. The Institute shares Boyer Hall with the Molecular Biology Institute, but some PIs and cores are housed in adjacent buildings.
The 6 Core Technology Centers are: the X-ray Diffraction Core, the Macromolecular Crystallization Core, the NMR Core, the Computational Biology Core, the Biological Instrumentation Core, and the Protein Expression Core. Each of these cores operates with support from a mosaic of sources, as well as DOE support. Each has a faculty Director and a professional manager. The Macromolecular Crystallization Core, organized by PI Bowie is associated with the X-ray Diffraction Core. In the last year, this facility performed roughly 1million crystallization experiments, accounting in part for the high productivity of the X-ray Core. The Biochemical Instrumentation Core is run in partnership with the Department of Chemistry and Biochemistry. It offers various spectroscopies, plasmon resonance, thermochemical titration, and so forth. The Computational Biology Core runs three computer clusters and serves scores of researchers in Boyer Hall. The NMR Core is located within the instrument wing of the Department of Chemistry, and like the other cores requires support from several sources. The Protein Expression Core provides expertise and service in molecular cloning and bacterial expression. It carries out much training of UCLA undergraduates in research. In addition, PI Weiss directs a heavily used Fluorescence Microscopy Core under the auspices of the California Nanosystems Institute.
The Bowie laboratory is developing an alternative to microbial metabolic engineering for the production of natural products and biofuels. To avoid the complex challenges and limitations of re-engineering metabolic pathways and producing novel chemical inside cells, the Bowie lab is developing ‘synthetic biochemistry’ approaches for production, where the cells are circumvented and biochemical pathways are built in the a reaction vessel. Systems that operate for long time periods and produce high yields of desirable chemicals have been produced.
The Clubb laboratory is studying how eubacteria display proteins and polymers on their surface. The goal is to leverage this knowledge to create surface‐engineered bacteria and materials that will be useful in achieving lignocellulosic biofuel production and bioremediation objectives. Novel technologies for enzyme-based protein tagging are also being developed.
The Eisenberg laboratory is working on new technologies for studying the structures of proteins that are inherently difficult to analyze in atomic detail because they cannot be produced in sufficient quantity or they cannot be coaxed into large enough crystals, or they are inherently impossible to crystallize, such as fibrils. Methods are being developed for analyzing diffraction from crystals as small as a few hundred nanometers, and for encapsulating peptides within well-ordered crystalline frameworks for diffraction.
The Gunsalus lab is investigating the anaerobic metabolism and key food chain intermediates in nature by model syntrophic microbes and their community partners. The goals are to identify and document previously unrecognized microbial pathways and enzymes needed for uptake and metabolism of model syntrophic substrates. The group is also examining how the methanogenic partners support the syntrophic lifestyle that requires nutrient exchange using defined microbial communities.
The Kosuri lab is developing new methods that accelerate progress in biology and biological engineering, focusing on large‐scale DNA synthesis and multiplexed measurements to establish very high‐throughput ways to explore sequence to function relationships in biology. Current work is providing rich new insights into phenomena ranging from protein evolution to the high-throughput mapping of receptor-ligand interactions.
The Loo laboratory is working to elucidate microbial cell physiology and regulation by monitoring the types and levels of proteins and of the modifications decorating them. Quantitative proteomics techniques are being developed and employed to measure protein abundances, while extensive data mining of tandem mass spectrometry datasets supports the exploration of novel post‐translational modifications in poorly‐studied microbes.
The Merchant group is taking advantage of genome‐sequencing based approaches for discovery of new components and functions related to photosynthesis and chloroplast biology. Large collection of RNA‐Seq datahas for Chlamydomonas are being exploited to deduce the functions of the many unannotated and uncharacterized proteins encoded in the algal genomes. The Merchant lab is also sequencing green algal genomes to use comparative phylogenomic approaches for discovery of components involved in metal homeostasis, photosynthesis and photobiology.
The Pellegrini group is developing and implementing approaches for the assembly and annotation of algal and plant genomes using new sequencing technologies. The group is developing and applying new tools to combine RNA‐seq data with de novo gene prediction pipelines to annotate genome and to facilitate the assignment and interpretation of functions for uncharacterized proteins.
The Rodriguez group is developing new approaches in electron diffraction for the determination of macromolecular structures from nano‐scale crystalline assemblies. The group is expanding the limits of electron diffraction toward smaller, partially crystalline assemblies, and developing new approaches to phasing electron diffraction patterns. These methods could make possible the structural characterization of scarce samples and those that remain a challenge to crystallize for evaluation by conventional methods.
The Weiss group is working to develop and characterize self‐assembling, membrane‐embedded voltage sensors based on semiconductor nanocrystals functionalized with α‐helical transmembrane peptides, phospholipids, or artificial membrane proteins.
The Yeates group is developing methods for designing novel protein assemblies for applications involving enzymes and new imaging technologies. Materials being designed include finite structures like ‘protein cages’ assembled from multiple copies of one or more types of proteins or enzyme molecules, and extended materials in two or three-dimensions. An important recent advance is the design of scaffolds for imaging small proteins by cryo-electron microscopy.
- Biochemical Instrumentation
- Computation Biology
- Protein Expression
- X-ray Diffraction
- Macromolecular Crystallization
- Joe Loo
- Chris Lee
- Juli Feigon/Robert Clubb
- James Bowie
- Todd Yeates
- James Bowie
- Martin Phillips, firstname.lastname@example.org
- Duilio Cascio, email@example.com
- Robert Peterson, firstname.lastname@example.org
- Mark Arbing, email@example.com
- Duilio Cascio, firstname.lastname@example.org
- Duilio Cascio, email@example.com
By long-standing agreement between DOE and UCLA, the Institute enjoys a favorable returned overhead rate on grants to the Institute related to the DOE mission. These extra funds have been used to add new PIs to the Institute roster to intensify research in fields of interest to DOE, and to purchase occasional items of major equipment. They also cover administrative salaries, and emergency bridge funds to PIs.
Research areas being pursued within the Institute include: advanced biofuels; carbon capture; the genomics, proteomics and properties of photosynthetic and other energy-related microbes; the structure and function of energy producing organelles; biomass degradation, and plant metabolism. Technology development in the Institute includes: tools; for algal and soil genomics, new methods of gene and protein identification and understanding of RNA regulation, tools for synthetic biology, and methods for microcrystallography and protein design.
The Institute maintains a web site (http://www.doe-mbi.ucla.edu/) which offers an array of services to Institute researchers and the world-wide scientific community. These services include 8 locally compiled databases including the well cited Database of Interacting Proteins. Also offered are an array of servers to aid in structure determination, validation, and functionation. Among the most popular servers are the SAVES structure validation server, the Merohedral Twinning Server, and the SER (Surface Entropy Reduction) Server for identification of mutations designed to enhance protein crystallizability. Maintenance of the web site is the responsibility of Webmaster, Thomas Holton, Holton@mbi.ucla.edu.
Although at UCLA instruction is the responsibility of departments, PIs of the UCLA-DOE Institute offer several courses for training in the technologies developed and used in the Institute. The course Structural Molecular Biology is offered by Clubb, Eisenberg, Feigon, and Yeates for training in methods of determination of atomic structures. This course includes a hands-on laboratory segment, employing the technology cores of the Institute which prepares students for use of the Cores in their research projects. Liao has organized a course on advanced biofuels, which calls on several Institute PIs, Associates, and professional staff for lectures. PIs Lee and Pellegrini offer courses in bioinformatics, PI Merchant in plant biochemistry, and PI Loo offers a course in mass spectrometry and proteomics.