DOE Joint Genome Institute

  • COVID-19
  • About Us
  • Contact Us
  • Our Science
    • DOE Mission Areas
    • Science Programs
    • Science Highlights
    • Scientists
    A vertical tree stump outdoors with about a dozen shiitake mushrooms sprouting from its surface.
    Tracing the Evolution of Shiitake Mushrooms
    Understanding Lentinula genomes and their evolution could provide strategies for converting plant waste into sugars for biofuel production. Additionally, these fungi play a role in the global carbon cycle.

    More

    Soil Virus Offers Insight into Maintaining Microorganisms
    Through a collaborative effort, researchers have identified a protein in soil viruses that may promote soil health.

    More

    Data yielded from RIViT-seq increased the number of sigma factor-gene pairs confirmed in Streptomyces coelicolor from 209 to 399. Here, grey arrows denote previously known regulation and red arrows are regulation identified by RIViT-seq; orange nodes mark sigma factors while gray nodes mark other genes. (Otani, H., Mouncey, N.J. Nat Commun 13, 3502 (2022). https://doi.org/10.1038/s41467-022-31191-w)
    Streamlining Regulon Identification in Bacteria
    Regulons are a group of genes that can be turned on or off by the same regulatory protein. RIViT-seq technology could speed up associating transcription factors with their target genes.

    More

  • Our Projects
    • Search JGI Projects
    • DOE Metrics/Statistics
    • Approved User Proposals
    • Legacy Projects
    A panoramic view of a lake reflecting a granite mountain.
    Genome Insider: Methane Makers in Yosemite’s Lakes
    Meet researchers who sampled the microbial communities living in the mountaintop lakes of the Sierra Nevada mountains to see how climate change affects freshwater ecosystems, and how those ecosystems work.

    Listen

    A light green shrub with spiny leaves, up close.
    Genome Insider: A Shrubbier Version of Rubber
    Hear from the consortium working on understanding the guayule plant's genome, which could lead to an improved natural rubber plant.

    Listen

    The switchgrass diversity panel growing at the Kellogg Biological Station in Michigan. (David Lowry)
    Mapping Switchgrass Traits with Common Gardens
    The combination of field data and genetic information has allowed researchers to associate climate adaptations with switchgrass biology.

    More

  • Data & Tools
    • IMG
    • Data Portal
    • MycoCosm
    • PhycoCosm
    • Phytozome
    • GOLD
    iPHoP image (Simon Roux)
    iPHoP: A Matchmaker for Phages and their Hosts
    Building on existing virus-host prediction approaches, a new tool combines and evaluates multiple predictions to reliably match viruses with their archaea and bacteria hosts.

    More

    Abstract image of gold lights and squares against a black backdrop
    Silver Age of GOLD Introduces New Features
    The Genomes OnLine Database makes curated microbiome metadata that follows community standards freely available and enables large-scale comparative genomics analysis initiatives.

    More

    Graphical overview of the RNA Virus MetaTranscriptomes Project. (Courtesy of Simon Roux)
    A Better Way to Find RNA Virus Needles in the Proverbial Database Haystacks
    Researchers combed through more than 5,000 data sets of RNA sequences generated from diverse environmental samples around the world, resulting in a five-fold increase of RNA virus diversity.

    More

  • User Programs
    • Calls for Proposals
    • Special Initiatives & Programs
    • Product Offerings
    • User Support
    • Policies
    • Submit a Proposal
    Green plant matter grows from the top, with the area just beneath the surface also visible as soil, root systems and a fuzzy white substance surrounding them.
    Supercharging SIP in the Fungal Hyphosphere
    Applying high-throughput stable isotope probing to the study of a particular fungi, researchers identified novel interactions between bacteria and the fungi.

    More

    Digital ID card with six headshots reads: Congratulations to our 2022 Function Genomics recipients!
    Final Round of 2022 CSP Functional Genomics Awardees
    Meet the final six researchers whose proposals were selected for the 2022 Community Science Program Functional Genomics call.

    More

    croppe image of the JGI helix sculpture
    Tips for a Winning Community Science Program Proposal
    In the Genome Insider podcast, tips to successfully avail of the JGI's proposal calls, many through the Community Science Program.

    Listen

  • News & Publications
    • News
    • Blog
    • Podcasts
    • Webinars
    • Publications
    • Newsletter
    • Logos and Templates
    • Photos
    2022 JGI-UC Merced interns (Thor Swift/Berkeley Lab)
    Exploring Possibilities: 2022 JGI-UC Merced Interns
    The 2022 UC Merced intern cohort share how their summer internship experiences have influenced their careers in science.

    More

    image from gif that shows where in the globe JGI fungal collaborators are located.
    Using Team Science to Build Communities Around Data
    As the data portals grow and evolve, the research communities further expand around them. But with two projects, communities are forming to generate high quality genomes to benefit researchers.

    More

    Cow Rumen and the Early Days of Metagenomics
    Tracing a cow rumen dataset from the lab to material for a hands-on undergraduate research course at CSU-San Marcos that has since expanded into three other universities.

    More

News & Publications
Home › News Releases › Freedom and Flexibility: Thinking Outside the Cell for Functional Genomics

April 3, 2018

Freedom and Flexibility: Thinking Outside the Cell for Functional Genomics

Latest JGI-Funded Technology Development Proposal Focuses on Cell-Free Systems

Over the past two decades, the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, has transitioned from a high-throughput genome sequencing center to a national user facility that provides researchers around the world with access to sequencing and computational analysis capabilities on projects relevant to the DOE missions of energy and environmental challenges. Along with advances in sequencing technologies and capacities, JGI has developed capabilities such as single-cell genomics, synthetic biology, and metabolomics to move beyond generating a DNA sequence to understanding gene functions for a myriad of applications.

The cell-free systems approach outlined in the proposal starts by lysing pre-optimized cells from selected strains, and then working with the lysates from these strains to express genes and pathways of interest in cell-free platforms (CFPS) which can be mixed in cocktails of varying ratios for easily and rapidly characterizing novel and improved pathways, speeding up the “build” and “test” portion of the design-build-test (DBT) cycle. (Diagram: Mike Jewett)

The cell-free systems approach outlined in the approved ETOP proposal starts by lysing pre-optimized cells from selected strains, and then working with the lysates from these strains to express genes and pathways of interest in cell-free platforms (CFPS) which can be mixed in cocktails of varying ratios for easily and rapidly characterizing novel and improved pathways, speeding up the “build” and “test” portion of the design-build-test (DBT) cycle. (Diagram: Ashty Stephen Karim)

“JGI’s strategic direction is to translate genomic information into functional understanding,” noted Director Nigel Mouncey. “Today, the scale and cost of DNA sequencing have afforded the generation of an unprecedented level of gene and genome information for which relatively little is known regarding function. Thus, there is a critical need to rapidly, and at scale, assign validated function of genes, pathways and genomes.”

Cell-based tests to determine metabolic function are challenging due to the need for cell growth, complex regulatory mechanisms, interference with or from other metabolic pathways and cellular processes. The latest proposal approved through the JGI’s Emerging Technologies Opportunity Program (ETOP) is led by Hal Alper of the University of Texas at Austin and Michael Jewett of Northwestern University. Aided by nearly $500,000 in funding over two years from the JGI, the project aims to develop an optimized cell-free platform that will enable researchers to speed up the “build” and “test” portion of the design-build-test-analyze cycle in synthetic biology. Cell-free systems have been used successfully for individual protein expression over decades, but more recent applications have focused on enzyme screening, metabolic pathway design and prototyping and immune system characterization.

Hal Alper, UT Austin

Hal Alper, UT Austin (courtesy photo)

“What we’re trying to develop is a generic platform that’s pathway-agnostic, a seamless pipeline from DNA design to prototype,” said Alper. “It’s a tool for both discovery and understanding, but always a way to speed up cell engineering.”

Launched in 2013, the ETOP aims to bring new technologies developed at other institutions into the JGI, making them available to its users for energy and environment applications and adding value to the high throughput sequencing and analysis currently being done for JGI users. (Click here for the list of previously approved proposals.)

The cell-free systems approach outlined in the proposal starts by lysing pre-optimized cells from selected strains, and then working with the lysates from these strains to express genes and pathways of interest which can be mixed in cocktails of varying ratios for easily and rapidly characterizing novel and improved pathways. Alper noted that this is a collaborative effort in which their labs will be handing off the technology development several times throughout the timeframe to enable progress.

“People have used cell-free frameworks to understand biochemistry for decades. What’s new is idea of treating a pathway as something that can be built from enzyme cocktails,” said Jewett. “In our design-build-test cycle, the unit isn’t a plasmid or a construct, but a lysate enriched with pathway enzymes. You have freedom and flexibility; direct access to reaction conditions because you don’t have cell walls, and it’s useful for non-model organisms. This can accelerate design loops and can lead to the question, rather than taking 10,000 shots on goal in a month, can we do it in a week?”

Mike Jewett, Northwestern University

Mike Jewett, Northwestern University (courtesy photo)

“This ETOP will develop novel and scaleable cell-free expression platforms that are optimized for particular key nodes of metabolism and will be demonstrated for a range of biosynthetic genes and pathways,” said Mouncey. “This technology is highly complementary to existing capabilities at JGI, and once in-house, will be combined in novel integrative workflows that allow for sophisticated genome mining to DNA synthesis to cell-free expression to high-throughput metabolomics to high-performance computing to characterize the function of 1000s of genes. Working with the leaders in this exciting field will lead to highly impactful and valuable technology for our Users.”

Jewett added that the cell-free systems framework wasn’t even possible two years ago. He cited the confluence of advances in DNA synthesis, improvements in cell-free biosynthesis capabilities, and genome engineering tools including novel strategies such as multiplexed CRISPR tools that have enabled this new platform.

“We hope to draw in researchers from the broader community that can leverage these new tools within the JGI,” he added.

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to print (Opens in new window)

The U.S. Department of Energy Joint Genome Institute, a DOE Office of Science User Facility at Lawrence Berkeley National Laboratory, is committed to advancing genomics in support of DOE missions related to clean energy generation and environmental characterization and cleanup. JGI provides integrated high-throughput sequencing and computational analysis that enable systems-based scientific approaches to these challenges. Follow @jgi on Twitter.

DOE’s Office of Science is the largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit science.energy.gov.

Filed Under: News Releases

More topics:

  • COVID-19 Status
  • News
  • Science Highlights
  • Blog
  • Webinars
  • CSP Plans
  • Featured Profiles

Related Content:

JGI announces 2023 CSP Functional Genomics awardees

Digital index card with JGI logo reads: Community Science Program (FY23) Congratulations to our CSP Functional Genomics recipients! Picture from left to right: (top) Thom Booth, Gabriel Castrillo, Han Li; (bottom) Jorge A. Marchand, Emre Özdemir, Fong Tian Wong

Researching and Solving Real-World Problems with the 2023 JGI-UC Merced Interns

2023 JGI-UC Merced interns (Zhong Wang/Berkeley Lab)

RECAP: Multi-Omic Journeys with 2023 JGI Annual Meeting Keynotes

Bruce Hungate stands at a podium and gesticulates as he discusses microbes.

For the Tiniest Archaea, A Genomic Switch of Friend or Foe

A grey microscopy photo taken at micron-scale. Microbes shown are small, round and slightly spiky in shape.

Doubling Down on Known Protein Families

An illustration of a microscope emitting a beam of light that hits a small, nondescript item.

The JGI announces 2024 awardees for our Community Science Program annual call

A series of headshots: From left to right: [above] Olivia Ahern, Adriana Corales, Hugh Cross, Megan DeMarche, Joanne Emerson, Matthew Hudson, Megan Keller and Julia Kelliher; [below] Vassili Kouvelis, Seppe Kuehn, Tesfaye Mengiste, Egbert Schwartz, Hannah Schulman, Bram Stone and Jana Voriskova
  • Careers
  • Contact Us
  • Events
  • User Meeting
  • MGM Workshops
  • Internal
  • Disclaimer
  • Credits
  • Policies
  • Emergency Info
  • Accessibility / Section 508 Statement
  • Flickr
  • LinkedIn
  • RSS
  • Twitter
  • YouTube
Lawrence Berkeley National Lab Biosciences Area
A project of the US Department of Energy, Office of Science

JGI is a DOE Office of Science User Facility managed by Lawrence Berkeley National Laboratory

© 1997-2023 The Regents of the University of California