Events

  • October 4, 2021

    EBRC SPA presents Follow the Money Panel

    The EBRC Student and Postdoc Association is hosting a panel discussion called Follow the Money for researchers to understand the science funding pipeline for engineering and synthetic biology.

  • Climate and Sustainability Roadmap Virtual Writing Workshop 7: December 13th

    Climate and Sustainability Roadmap Virtual Writing Workshop 7
    Monday, December 13th, 2021
    12 pm – 3 pm ET | 9 am – 12 pm PT

    Register Here

    Registration closes December 11th, 2021

    Workshop Activities and Details Coming Soon!

    We are excited to engage with EBRC members and the broader research community on this important roadmapping effort. We welcome workshop participation from academic, industry, and government scientists and engineers, research & development leadership, students and postdocs, and other stakeholders.

    For more information about the roadmap or workshop, please contact Sifang Chen ([email protected])

  • Climate and Sustainability Roadmap Virtual Writing Workshop 6: December 1st

    Climate and Sustainability Roadmap Virtual Writing Workshop 6
    Wednesday, December 1st, 2021
    11 am – 2 pm ET | 8 am – 11 am PT

    Register Here
    Registration closes November 29th, 2021

    Workshop Activities and Details Coming Soon!

    We are excited to engage with EBRC members and the broader research community on this important roadmapping effort. We welcome workshop participation from academic, industry, and government scientists and engineers, research & development leadership, students and postdocs, and other stakeholders.

    For more information about the roadmap or workshop, please contact Sifang Chen ([email protected])

     

  • Climate and Sustainability Roadmap Virtual Writing Workshop 5: November 15th

    Monday, November 15th, 2021
    11:00am-2:00pm ET | 8:00am-11:00am PT

    Register Here
    Registration closes November 13th, 2021

    Workshop Activities and Details Coming Soon!

    We are excited to engage with EBRC members and the broader research community on this important roadmapping effort. We welcome workshop participation from academic, industry, and government scientists and engineers, research & development leadership, students and postdocs, and other stakeholders.

    For more information about the roadmap or workshop, please contact Sifang Chen ([email protected])

  • August 24, 2021

    Synthetic Biology Young Speaker Series (SynBYSS)

    This virtual seminar series, held every Thursday (11-12 am US ET | 8-9 am US PT), will feature presentations by early-career professionals. You can view all seminars on Zoom or […]

  • Climate and Sustainability Roadmap Virtual Writing Workshop 3: September 9th

    Thursday, September 9th, 2021
    1:00pm-4:00pm ET | 10:00am-1:00pm PT

    Register Here

    Registration closes September 7th, 2021

    Agenda: Click here

    We are excited to engage with EBRC members and the broader research community on this important roadmapping effort. We welcome workshop participation from academic, industry, and government scientists and engineers, research & development leadership, students and postdocs, and other stakeholders.

    Building off the first two workshops focusing on climate and environmental challenges, this third workshop will broaden our scope to include discussions on concrete and bold engineering biology solutions for long-term sustainable development and use of natural resources, while iterating on the opportunities and goals put forth in the previous workshops.

    For more information about the roadmap or workshop, please contact Sifang Chen ([email protected])

  • June 29, 2021

    Synthetic Biology Young Speaker Series (SynBYSS) nominations open!

    This virtual seminar series will feature presentations by early career professionals. Nominations will be accepted on a rolling basis.

  • 2019 Roadmap Assessment Workshop – Data Science

    Please join us at a virtual workshop to assess the Data Science: Data Integration, Modeling, and Automation technical theme of Engineering Biology.

    Friday, June 11, 2021
    12:00pm – 3:00pm Eastern | 9:00am – 12:00pm Pacific

    AgendaRegister Here

    This workshop will draw upon our survey results to assess technical progress in the context of the research milestones predicted in Engineering Biology, the 2019 EBRC technical research roadmap. This information will shape a narrative of the most pressing needs and challenges still facing engineering biology over the next decade.

    The workshop will inventory the degree of completion for each milestone, discuss technical and nontechnical barriers inhibiting progress, highlight new directions and avenues of research, and review social science dimensions associated with the development of technical goals. This will come in the form of a published report that will be adapted for public viewing.

    These virtual writing workshops for each technical theme (3 hours each) are focused on drafting and revising the assessment. They are organized as followed:

    • Introduction of the assessment, including the purpose, timing, and impact;
    • Brainstorming, informed by the results of our surveys, of the degree of completion for each research milestone, technical and nontechnical barriers inhibiting progress, and social science dimensions associated with the development of technical goals. We’ll also discuss new avenues and directions of research unanticipated by the roadmap;
    • Drafting and revising summaries of each of the above components.

    The report will be invaluable to policymakers and funders to understand the continued challenges faced by our researchers; to researchers to learn the critical research gaps preventing engineering biology progression; and for our EBRC community to assess the utility of our roadmaps.

    Hosted by Adam Arkin (UC Berkeley) and Nathan Hillson (LBNL)

     

  • 2019 Roadmap Assessment Workshop – Host Engineering

    Please join us at a virtual workshop to assess the Host Engineering: Host and Consortia Engineering technical theme of Engineering Biology.

    Thursday, June 10, 2021
    11:00am – 2:00pm Eastern | 8:00am – 11:00am Pacific

    AgendaRegister Here

    This workshop will draw upon our survey results to assess technical progress in the context of the research milestones predicted in Engineering Biology, the 2019 EBRC technical research roadmap. This information will shape a narrative of the most pressing needs and challenges still facing engineering biology over the next decade.

    The workshop will inventory the degree of completion for each milestone, discuss technical and nontechnical barriers inhibiting progress, highlight new directions and avenues of research, and review social science dimensions associated with the development of technical goals. This will come in the form of a published report that will be adapted for public viewing.

    These virtual writing workshops for each technical theme (3 hours each) are focused on drafting and revising the assessment. They are organized as followed:

    • Introduction of the assessment, including the purpose, timing, and impact;
    • Brainstorming, informed by the results of our surveys, of the degree of completion for each research milestone, technical and nontechnical barriers inhibiting progress, and social science dimensions associated with the development of technical goals. We’ll also discuss new avenues and directions of research unanticipated by the roadmap;
    • Drafting and revising summaries of each of the above components.

    The report will be invaluable to policymakers and funders to understand the continued challenges faced by our researchers; to researchers to learn the critical research gaps preventing engineering biology progression; and for our EBRC community to assess the utility of our roadmaps.

    Hosted by James Carothers (UW) and Ute Galm (Zymergen)

  • 2019 Roadmap Assessment Workshop – Engineering DNA

    Please join us at a virtual workshop to assess the Engineering DNA: Gene Editing, Synthesis, and Assembly technical theme of Engineering Biology.

    Thursday, June 3, 2021
    2:00pm – 5:00pm Eastern | 11:00am – 2:00pm Pacific
    Agenda

    Registration for this event is now closed. For more information, please contact [email protected]

    This workshop will draw upon our survey results to assess technical progress in the context of the research milestones predicted in Engineering Biology, the 2019 EBRC technical research roadmap. This information will shape a narrative of the most pressing needs and challenges still facing engineering biology over the next decade.

    The workshop will inventory the degree of completion for each milestone, discuss technical and nontechnical barriers inhibiting progress, highlight new directions and avenues of research, and review social science dimensions associated with the development of technical goals. This will come in the form of a published report that will be adapted for public viewing.

    These virtual writing workshops for each technical theme (3 hours each) are focused on drafting and revising the assessment. They are organized as followed:

    • Introduction of the assessment, including the purpose, timing, and impact;
    • Brainstorming, informed by the results of our surveys, of the degree of completion for each research milestone, technical and nontechnical barriers inhibiting progress, and social science dimensions associated with the development of technical goals. We’ll also discuss new avenues and directions of research unanticipated by the roadmap;
    • Drafting and revising summaries of each of the above components.

    The report will be invaluable to policymakers and funders to understand the continued challenges faced by our researchers; to researchers to learn the critical research gaps preventing engineering biology progression; and for our EBRC community to assess the utility of our roadmaps.

    Hosted by Rebecca Nugent (Twist Bioscience) and Howard Salis (Penn State)

  • 2019 Roadmap Assessment Workshop – Biomolecular Engineering

    Please join us at a virtual workshop to assess the Biomolecular Engineering: Biomolecule, Pathway, and Circuit Engineering technical theme of Engineering Biology.

    Tuesday, June 8, 2021
    11:00am – 2:00pm Eastern | 8:00am – 11:00pm Pacific

    Agenda

    Registration for this event is now closed. For more information, please contact [email protected]

    This workshop will draw upon our survey results to assess technical progress in the context of the research milestones predicted in Engineering Biology, the 2019 EBRC technical research roadmap. This information will shape a narrative of the most pressing needs and challenges still facing engineering biology over the next decade.

    The workshop will inventory the degree of completion for each milestone, discuss technical and nontechnical barriers inhibiting progress, highlight new directions and avenues of research, and review social science dimensions associated with the development of technical goals. This will come in the form of a published report that will be adapted for public viewing.

    These virtual writing workshops for each technical theme (3 hours each) are focused on drafting and revising the assessment. They are organized as followed:

    • Introduction of the assessment, including the purpose, timing, and impact;
    • Brainstorming, informed by the results of our surveys, of the degree of completion for each research milestone, technical and nontechnical barriers inhibiting progress, and social science dimensions associated with the development of technical goals. We’ll also discuss new avenues and directions of research unanticipated by the roadmap;
    • Drafting and revising summaries of each of the above components.

    The report will be invaluable to policymakers and funders to understand the continued challenges faced by our researchers; to researchers to learn the critical research gaps preventing engineering biology progression; and for our EBRC community to assess the utility of our roadmaps.

    Hosted by Chang Liu (UC Irvine) and Jesse Zalatan (UW)

  • EBRC Seminar Series – May 21, 2021 (4:00 PM ET)

    Please join us for an exciting seminar on May 21, 2021, from 4-5:00 PM ET. This is the final seminar in the 2021 EBRC Seminar Series.

    Speaker abstracts are below. The seminar is open to all, so please feel free to share this information with your colleagues.

    The seminar will be held on Zoom using the following link for all sessions:
    Zoom link: https://berkeley.zoom.us/j/97626552307?pwd=alVlS3dXM0lZYklYeE9zVXljWUI0UT09
    Meeting ID: 976 2655 2307
    Passcode: EBRC2021

     

    “Sequence-function analysis helps identify multiple pathways to enhance Phenylalanine Ammonia-Lyase (PAL) activity”

    Nikhil Unni Nair (Tufts University)

    Phenylalanine ammonia-lyases (PALs) non-oxidatively deaminate L-phenylalanine to trans-cinnamic acid (tCA) and are widely found associated with secondary metabolism in plants, bacteria, and fungi. Biocatalytic applications for natural product and fine chemical synthesis has driven the discovery, expression, characterization, and engineering of PALs. More recently, development of PALs for phenylketonuria (PKU) management and cancer therapy has further increased interest in engineering this class of enzymes. While there is a general understanding of how residues in the substrate-binding pocket contribute to specificity and turnover, led by rational mutagenesis studies, there is generally a poor understanding of how distal residues affect function. In general, outcomes from directed evolution can identify distal hotspots but there have only been two such studies with this enzyme. The first study resulted in modest improvement in activity whereas the other, conducted by us, identified residues within the active site only. Deep mutational scanning (DMS) can identify functional hotspots, and when coupled with directed
    evolution can accelerate engineering campaigns, although there are few examples of this approach. Further, DMS can provide a comprehensive map of sequence–function relationships to explore the protein fitness landscapes, uncover functionally relevant sites, improve molecular energy functions, and identify beneficial combinations of mutations for protein engineering. Though extensive body of research exists on function, structure, mechanism of PAL, a systematic study exploring the sequence-function space has not been attempted.

    Previously, we developed a growth-coupled enrichment for rapid screening of high-activity variants of AvPAL* (used to formulate the PKU drug Pegvaliase®) in E. coli. After a single round of directed evolution using this growth-coupled enrichment, we identified 2 active site mutations improved kcat < 2-fold. However, the sequence-function fitness landscape of AvPAL* remains to be explored. In this study, we achieve several outcomes. First, we obtained the detailed sequence-function landscape of PAL, to date, using DMS, identifying >60 mutational hotspots. Next, we picked seven sites for comprehensive single and multi-site saturation mutagenesis and we identified multi-site mutations with ~2.5-fold improvement in the kcat (and >3-fold increase in catalytic efficiency). We then explored the epistatic effect of these mutations, uncovering positive, neutral, and negative interactions among distal and proximal sites. Finally, to understand the mechanistic role of key mutations in hyperactive variants, we performed modelling studies and concluded that there are multiple pathways to enhance PAL catalytic activity, including, decreased root mean square fluctuation (RMSF) of substrate in the active site, greater proximity of the substrate to catalytic residues, and facilitated diffusion of the substrate to the active site, among others. In summary, this study significantly advances basic and applied enzymology of PALs, a heretofore understudied class of enzymes with a wide array of applications.

     

    Development of a yeast-based assay for bioavailable phosphorous
    Heather Shepherd (University of Notre Dame)

    Preventing eutrophication of inland freshwater ecosystems requires quantifying the phosphorous (P) content of the streams and rivers that feed them. Typical methods for measuring P assess soluble reactive P (SRP) or total P (TP) and require expensive analytical techniques that produce hazardous waste. Here we present a novel method for measuring the more relevant bioavailable P (BAP); this assay utilizes the growth of familiar baker’s yeast, avoids production of hazardous waste, and reduces cost relative to measurements of SRP and TP. The yeast BAP (yBAP) assay takes advantage of the observation that yeast density at saturating growth increases linearly with provided P. We show that this relationship can be used to measure P in freshwater in concentration ranges relevant to eutrophication. In addition, we measured yBAP in water containing known amount of fertilizer and in samples from agricultural waterways. We observed that the majority of yBAP values were between those obtained from standard SRP and TP measurements, demonstrating that the assay is compatible with real-world settings. The cost-effective and nonhazardous nature of the yeast-based assay suggests that it could have utility in a range of settings, offering added insight to identify water systems at risk of eutrophication from excess phosphorus.

     

    Engineering alternative degradation tags for synthetic circuits
    Prajakta Jadhav (South Dakota State University)

    The goal in synthetic biology is to build robust synthetic circuits in bacteria that are dynamic, highly regulated, and result in a unified response. In the last 20 years, the synthetic biology field has effectively leveraged transcriptional (RNA production) and translational (protein production) controls. However, protein degradation plays an important role in determining the half-life of proteins and regulating biological systems. Amino acid degradation tags are exploited to avoid a reliance on cell division for protein dilution and to build dynamic circuits. The most leveraged
    degradation tag in E. coli is the ssrA-tag, which is an 11-amino acid sequence that primarily target proteins for degradation by the ClpXP proteolytic system. However, the use of the ssrA-tag limits scalability and complexity especially in synthetic oscillators in bacteria due to itsmultiple proteolytic target recognition signals. Our goal is to build orthogonal oscillators that utilize degradation tags targeting to multiple proteases with no crosstalk. In this study, we aremodifying the ssrA-tag to change the substrate affinity and degradation rate and produce new
    synthetic oscillators. We hypothesize that changing the degradation rate can alter the output signal of the oscillator. We have tailored the ssrA-tag to reduce crosstalk between proteolytic systems to increase robustness and developed a variety of degradation tags. While many of these tags exhibited decreased or no change in degradation rates, two depicted significant increase. We further tested interesting candidates for crosstalk between proteolytic systems and identified a tag that display minimum to no crosstalk with other proteolytic systems. We aim to build and compare the output signals of different oscillators with novel tags in batch cultures and at the single-cell level. The design and implementation of these novel degradation tags will enable development of biological building blocks for increased complexity in synthetic circuits.

  • EBRC Seminar Series – May 13, 2021 (2:00 PM ET)

    Please join us for an exciting seminar on May 13, 2021, from 2-3:30 PM ET. This is the second of three seminars in the 2021 EBRC Seminar Series.

    Speaker abstracts are below. The seminar is open to all, so please feel free to share this information with your colleagues.

    The seminar will be held on Zoom using the following link for all sessions:
    Zoom link: https://berkeley.zoom.us/j/97626552307?pwd=alVlS3dXM0lZYklYeE9zVXljWUI0UT09
    Meeting ID: 976 2655 2307
    Passcode: EBRC2021

     

    TBD
    Aindrila Mukhopadhyay (Lawrence Berkeley National Lab)

    TBD

     

    “Non-canonical crRNAs derived from host transcripts enable multiplexable RNA detection by Cas9”
    Chunlei Jiao (Helmholtz Institute for RNA-based Infection Research)

    CRISPR nucleases are guided by CRISPR RNAs (crRNAs) that are naturally derived from CRISPR arrays. Here, we discovered that crRNAs could derive from cellular transcripts outside of the CRISPR-Cas locus in Campylobacter jejuni, and we exploit this discovery to achieve a novel means of multiplexed RNA detection. The discovery came from sequencing RNAs that preferentially bound to the Cas9 in C. jejuni (CjeCas9), revealing an unexpected set of RNAs that shared a motif complementary to the anti-repeat of the system’s tracrRNA. The size and composition of these bound RNAs resembled that of crRNAs, indicating that the full-length version of these RNAs base pair with the anti-repeat portion of the tracrRNA and undergo processing to form crRNA-like RNAs. We call these processed RNAs non-canonical crRNAs (ncrRNAs). Using a cell-free transcription-translation (TXTL) system, we found that some ncrRNAs could drive efficient and sequence-specific DNA cleavage by CjeCas9 and its natural tracrRNA. Given the known sequence flexibility within the repeat:anti-repeat stem for single- guide RNAs, we hypothesized that the anti-repeat portion of the tracRNA could be reprogrammed to convert any RNA-of-interest into a functional ncrRNA that guides Cas9 to its DNA target. Using DNA cleavage assays in TXTL and in E. coli, we found that reprogrammed
    tracrRNAs(Rptrs) designed to pair with different regions of an mRNA yielded efficient DNA cleavage not only for the CjeCas9 but also for the S. pyogenes Cas9 and the Streptococcus thermophilus CRISPR1 Cas9. Finally, based on the capability of Rptrs to link any RNA-of-interest to sequence-specific DNA cleavage, we established a multiplexed RNA diagnostic platform called LEOPARD (Leveraging Engineered tracrRNAs and On-target DNAs for PArallel RNA Detection). With LEOPARD, we achieved multiplexed detection of RNAs from different viruses including SARS-CoV-2 and other respiratory viruses in one reaction. We further distinguished SARS-CoV-2 and its D614G variant with single-nucleotide specificity in patient samples. These findings establish a previously unknown source of crRNAs and demonstrate the practical utility of LEOPARD for detecting numerous biomarkers in one test.

     

    “Developing a mathematical framework for controlling complex biological systems”
    Marcella Gomez (UC Santa Cruz)

    In this talk, we refer to the achievement of an intended and predicted response in a biological system as controlling biology. Such efforts are often guided by classical mechanistic models from first principles. The level of complexity of these systems makes it extremely difficult to develop mechanistic models that can account for all possible interactions and predict biological response. To overcome these challenges, we propose to move away from first principal methods and instead identify key leverage points in the targeted biological pathways that can be directly up or down regulated by external signaling molecules. These molecules can be controlled by a feedback algorithm and delivered in situ by a bioelectronic device. In recent work, we successfully implemented feedback control on human‐induced pluripotent stem cells (hiPSCs) to regulate the cell’s resting potential known to affect cell physiology and functions such as proliferation, differentiation, migration, and apoptosis, as well as cell–cell communication and large‐scale morphogenesis. This was achieved without use of a model nor training data. We further outline an approach to extend the method to more complex biological systems. In particular, we consider the task of accelerating wound healing.

     

    “The Promoter Calculator – A Sequence-to-Function Biophysical Model of Transcriptional Initiation for Sigma70 Promoters with Any Sequence”
    Travis La Fleur (Penn State)

    Engineering synthetic promoters with precision control has remained a challenge due to our inability to predict how a promoter’s sequence and DNA context controls its function and mRNA output. Here, we developed an accurate sequence-to-function model of transcriptional initiation that enables the automated design of synthetic promoters and the a priori prediction of cryptic promoters within natural systems – both of which are needed to advance Synthetic Biology towards genome-scale functional design. To do this, we combined oligopool synthesis, library-
    based cloning, and next-generation sequencing to construct and characterize 14,206 rationally designed sigma70 promoters in vitro. Measurements include transcriptional start site frequencies and overall mRNA levels. This approach enables highly-parallel characterization of constitutive promoter activity without confounding factors such as unintentional transcriptional regulation, non-sigma70 activity, and mRNA decay. These measurements, in combination with machine learning, were used to parameterize a thermodynamic model quantifying the
    interactions controlling transcription rate. For demonstration, the “Promoter Calculator” was used to accomplish three major tasks – accurate prediction of thousands of sigma70 promoters across various conditions, the de novo design of novel sigma70 promoters, and the identification of cryptic promoters internal to a genetic circuit. 4,350 highly non-repetitive promoters and 6,165 genome-integrated promoters characterized in vivo were accurately predicted by the model with Spearman Rank-Order Coefficients of .68 and .78, respectively. Promoters designed de novo using the Promoter Calculator were characterized in vivo exhibiting a 683-fold range in expression resulting in a Pearson Correlation Coefficient of .85. The Promoter Calculator was used to analyze a genetic circuit containing 11 circuit promoters and 29 cryptic promoters. The model identified 29 sigma70 promoters out of 40 observed promoters (72.5% accurate), including 10/11 circuit promoters and 19/29 cryptic promoters. The Promoter Calculator facilitates context-aware, rational promoter design without relying on a fixed table of pre-characterized sequences while serving as a powerful tool in promoter identification.

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