Seminar Series
Upcoming Events
Past Events
Dr. Marilyn Lee, DEVCOM Chemical Biological Center to present CSB seminar on Wednesday, March 29th, 2023 at 1:00pm in Ryan Hall 4003.
"Cell-free protein synthesis for bio-functionalized materials"
Cells are a basic building block of biology, but what can transcription and translation processes do when we think outside the cell? Cell-free biological systems provide an open environment that illuminates new opportunities, particularly in biomaterials science. Conferring dynamic and specific bio-functions like sensing and decontamination to synthetic materials has been a long-sought goal. Yet, microbial viability, membrane transport barriers, and other cellular features post difficult engineering challenges. Cell-free systems can confer many of these functions without the limitations if living cells, providing direct interaction between materials and the desired enzymes, while also exhibiting enhanced stability for some material processing steps. Pioneering studies to functionalize materials with cell-free protein synthesis (CFPS) reactions began with absorbing liquid reactions into porous materials such as paper or hydrogels. Our work has extended these studies into solvent and heat cast polymer plastics, with potential applications in coatings, wipes, wearables, and personalized hazard detection. In this presentation I will highlight CBC’s contributions towards cell-free functionalized materials and a fresh outlook for engineering biologically driven devices.
Dr. David Garcia, DEVCOM Chemical Biological Center to present CSB seminar on Thursday, March 30th, 2023 at 11:00am in Ryan Hall 4003.
"High-Throughput Optimization of Cell-Free Systems"
Cell-free extracts (CFE) have developed into a high-throughput and scalable tool for synthetic biology and metabolic engineering with applications across disciplines ranging from biomanufacturing to education. However, the ability to generate data that informs the large-scale production of cell-free systems remains challenging as laboratory scale methods are often ill-suited to replicating scaled biomanufacturing. To help resolve these problems, we first present a new high-throughput screening method leveraging acoustic liquid handling to optimize the function and shelf-stability of a low-cost paper-based biosensor. Second, we present on the optimization of a cell-free metabolic engineering platform for the production of protoporphyrins. In both of these case studies, our approach first optimizes the performance of a CFE formulation that was initially non-functional, then further optimizes it for shelf-stability and titer. Finally we showcase how this information is leveraged towards the large-scale production of nucleic acid biosensors and the valuable precursor protoporphyrin IX.
Dr. Martin Fussenegger, ETH Zurich and University of Basel, Basel, Switzerland to present CSB seminar on Monday, November 7, 2022 at 4:00pm in Tech LR4 and Tuesday, November 8, 2022 at 12:00pm in Lurie Hughes Auditorium
"Toward A World of ElectroGenetics"
With the advent of the internet of things, interconnected electronic devices are starting to dominate our daily lives and are reaching the control complexity of living systems, and yet work radically different: While human metabolism uses ion gradients across insulated membranes to simultaneously process slow analog chemical reactions and communicate information in multicellular systems via soluble or volatile molecular signals, electronic devices use multicore central processing units to control the flow of electrons through insulated metal wires with gigahertz frequency and communicate information across networks via wired or wireless connections. While analog biological systems and digital electronic devices efficiently work in their respective worlds there are no efficient interfaces between electronics and genetics. We will report our first attempts to design direct electro-genetic interfaces and our progress toward a world of ElectroGenetics and the internet of the body.
Dr. Eduardo Agosin Trumper, Pontificia Universidad Católica de Chile, Santiago, Chile to present CSB seminar on Wednesday, August 31, 2022 at 11:00am in Tech M345
"Heterologous production of plant growth hormones in yeast"
Cytokinins are a family of phytohormones that regulate plant growth processes. Trans-zeatin (tZ) and isopentenyladenine (iP), together with their sugar conjugates (glucosides and ribosides) are the most prevalent natural cytokinins. They have a wide range of applications in crop improvement and management, particularly in the regulation of fruit size and quality. The current price of commercial cytokinins has hampered their massive applications in agriculture. Using synthetic biology and metabolic engineering tools, we constructed a yeast cell factory able to produce 1,5g/L of cytokinins in fed-batch fermentation, an improvement of a 100-fold in phytohormone titer compared with the initial strain. We are currently scaling up the process to commercial scale.
Dr. Claudia Vickers (Queensland University of Technology) to present CSB seminar on Friday, May 6, 2022 at 9:00am in Tech L361
"Synthetic Biology Tools To Understand And Control Subcellular Biocatalysis"
Effective redirection of carbon at specific metabolic nodes requires a suite of tools that can deliver useful outcomes under a wide variety of different conditions. Metabolic flux control mechanisms are commonly exerted at pre-translational levels; however, many metabolic conditions demand protein-mediated solutions that more directly and/or more rapidly influence catalytic conditions. We use isoprenoid (terpene/terpenoid) production as a model system to investigate these challenges. Isoprenoids are an extremely large and diverse group of natural compounds with myriad industrial uses, ranging from specialized applications (e.g. pharmaceuticals, fine chemicals, additives) through to bulk chemicals (e.g., colourants, fragrances, industrial polymers, agricultural chemicals, and fuel replacements). To control carbon flux at specific metabolic nodes for delivery of different classes of isoprenoids we have developed a variety of molecular tools that can be used to redirect metabolism at metabolic nodes. These include co-location of pathway enzymes using scaffolds (including nanocompartments) to alleviate toxicity effects, increase titres, and alter the product profile of promiscuous enzymes, and protein-based biosensors to understand metabolite accumulation. Here we will explore these tools and their application for metabolic engineering of isoprenoid production pathways. Using these approaches, we can effectively control and balance metabolism to deliver g/L titres of target isoprenoids.
Dr. Tom Ellis (Imperial College London, UK) to present CSB seminar on Friday, December 10, 2021 at 10:00am via Zoom
"Patterning Grown Materials With DNA-Programmed Properties"
Synthetic biology offers a new opportunity to learn how to write DNA programs that make new materials with diverse functions and properties. Our group uses microbes proficient in producing the base polymer of all plants – cellulose – and writes modular DNA programs to control and diversify the materials these cells produce. We use synthetic biology to engineer bacteria and yeast to sense spatial constraints, chemical signals and light, and in response change their behaviour and produce proteins as the material is grown. Recreating the yeast-bacteria relationship seen naturally in Kombucha tea fermentation, we recently described a synthetic co-culture that grows new cellulose-based materials with biosensor and catalytic properties and showed patterning of this material was possible with light-induced gene expression. In new work, we have extended optogenetic engineering to also work in the material-producing bacteria, now giving us the ability to pattern grown materials with high fidelity and to enzymatically modify these material as they are made. Our approach creates a new class of engineered living materials, with applications possible in healthcare, sustainability and fashion and textiles.
Dr. James Carothers (University of Washington) to present CSB seminar on Thursday, November 18, 2021 at 11:00am via Zoom
"Multi-Layer CRISPRa/i Circuits for Dynamic Genetic Programs in Cell-Free and Bacterial Systems"
CRISPR-Cas transcriptional circuits hold great promise as platforms for engineering metabolic networks and information processing circuits. Historically, CRISPR control systems in prokaryotes have been limited to CRISPRi repression. Creating approaches to integrate CRISPRa for transcriptional activation in these systems would greatly expand CRISPR circuit design space. We have developed design principles for engineering prokaryotic CRISPRa/i genetic circuits with network topologies specified by guide RNAs. We have demonstrated that multi-layer CRISPRa/i cascades and feed-forward loops can operate through the regulated expression of guide RNAs in cell-free expression systems and E. coli. We have shown that CRISPRa/i circuits can program complex functions by designing type 1 incoherent feedforward loops to serve as fold-change detectors and tunable pulse-generators. The correspondence between predicted effects of CRISPRa/i circuit tuning actions and measured functions suggests that these circuits could be assembled into larger and more complex networks. In my presentation, I will show how component characteristics can be related to network properties such as depth, width, and speed, and outline a framework for building scalable CRISPRa/i circuits as regulatory programs in cell-free expression systems and in industrially-promising bacteria.
Dr. Rebecca Schulman (Johns Hopkins University) to present CSB seminar on Wednesday, October 20, 2021 at 12:00pm via Zoom
"Biochemical Networks for Controlling the Growth and Metamorphosis of Soft Materials"
Complex cellular behaviors such as motion and division are directed by far-from-equilibrium chemical networks that regulate the assembly and reconfiguration of a cell’s architecture at the molecular scale. The ability to program the evolution of synthetic materials using designed chemical networks in fashions similar to the way biological networks regulate a cell and tissue architecture could be a route to building radically new materials that could grow into specific shapes, heal, or adapt to their environments. Building and improving these systems might also provide new perspectives on the structural organization of cells and tissues and on the genetic and signal transduction networks that regulate these cell and tissues’ structures and therefore, functions.
We have been developing synthetic components that dynamically assemble and change the shapes of biomolecular materials, specifically hydrogels and semiflexible polymer networks, and corresponding synthetic chemical networks that can regulate these materials’ dynamic assembly. I will describe how different biomolecular signals can induce different dynamic polymerization and depolymerization processes in these materials and how chemical networks can be coupled to these materials to induce dynamic material behavior. To understand what new behaviors can arise in these systems when their chemical networks become large and complex, we have recently developed integrated synthetic in vitro genetic regulatory networks consisting of oligonucleotide templates, T7 RNA polymerase and an RNase. These networks can consist of tens of different interconnected network elements and could be used to build synthetic regulatory networks of complexities comparable to those of simple viruses or those that construct macromolecular complexes inside cells.
Dr. Elizabeth Sattely (Stanford University) to present CSB seminar on Thursday, May 4, 2021 at 1:00pm via Zoom
"Discovery and Engineering of Plant Chemistry for Plant and Human Health"
Plants are some of the best chemists on the planet and produce an impressive array of small molecules. We are inspired by the fact that humans have become extraordinarily reliant on plant-derived molecules for food, medicine, and energy. However, remarkably little is known about how plants make these molecules, limiting our ability to engineer and optimize plant metabolic pathways. New plant genome sequences and synthetic biology tools have enabled three research areas under investigation in my lab: 1) Identifying the minimum set of enzymes required to make known plant-derived molecules and non-natural derivatives through metabolic engineering, and 2) discovering new molecules from plants, and 3) developing new strategies to enhance plant fitness. In this talk, I will describe some of our recent efforts to accelerate the discovery of complete plant pathways for known and novel molecules, not only in the model plant Arabidopsis but also in non-model plants.
Dr. Stanley Qi (Stanford University) to present CSB seminar on Tuesday, April 20, 2021 at 1:00pm via Zoom
"Programmable Genome Engineering for Synthetic Biology, Cell Engineering and Therapy"
Synthetic control of the genome is important for studying the genome function and developing new therapies. We focus on deploying the precise nuclease-dead dCas system to develop tools for the control of genome-level transcription, epigenetics, and 3D genome structure. We apply these technologies to understand the noncoding genome function via combined perturbation, imaging and sequencing. We apply RNA-targeting CRISPR molecules to recognize and cleave RNA viruses including SARS-CoV-2. In this talk, I will cover our efforts on expanding the CRISPR toolbox for synthetic biology and cell engineering.
Dr. Karmella Haynes (Emory University) to present CSB seminar on Tuesday, March 9, 2021 at 1:00pm via Zoom
"Chromatin Engineering For Epigenetic Therapy In Triple Negative Breast Cancer "
Mounting evidence from genome-wide comparisons of chromosome packaging and gene expression in healthy versus cancer cells suggests that epigenetic hyper-repression, rather than genetic mutation in many cases, supports cancer aggressiveness. Aberrant behavior of the chromatin system (genomic DNA, and nuclear RNA and proteins) has been implicated as a driver of metastasis and drug resistance. Since the early 1990’s small compounds have been used to disrupt hyper-repressed chromatin to simultaneously co-activate groups of therapeutic genes in cancer cells. However, it is difficult to customize the biological activity of these small compound inhibitors, and they do not directly mediate RNA PolII activity at silenced tumor suppressor genes. To address these limitations, our lab has designed synthetic reader-actuator (SRA) fusion proteins that bind epigenetic marks within chromatin. The first SRA we have designed and tested in cancer cells, “Polycomb-based transcription factor” (PcTF), reads histone modifications through a protein-protein interaction between its N-terminal Polycomb chromodomain (PCD) motif and trimethylated lysine 27 of histone H3 (H3K27me3). The C-terminal VP64 domain of PcTF recruits endogenous activators to silenced targets. We showed in previous work that dozens of genes become consistently activated from 24 - 72 hours after PcTF-overexpression in one triple negative breast cancer cell line (BT-549). This talk will highlight our most recent efforts to co-activate a set of 99 tumor suppressor genes that regulate proliferation, immune response, and epithelial cell fate in triple negative breast cancer. We observed that PcTF activates key tumor suppressor genes and leads to reduced proliferation and viability in BT-549 cells in vitro. The anti-proliferative effect can be observed in as little as 24 to 48 hours, compared to 3 - 6 day treatments required for epigenetic inhibitor drugs. To further enhance the activity of PcTF, we are developing a miniaturized chromatin-binding array to screen for SRA variants with stronger affinity for H3K27me3.
Dr. David Liu (Harvard University) to present CSB seminar on Wednesday, December 9, 2020 at 12:00pm via Zoom
"Base Editing and Prime Editing: Genome Editing Without Double-Strand Breaks"
Most genetic variants that contribute to disease are challenging to correct efficiently and without excess byproducts in various cell types using programmable nucleases. In this lecture I describe the development of two approaches to precision genome editing that do not require double-strand DNA breaks, donor DNA templates, or HDR. Through a combination of protein engineering and protein evolution, we developed two classes of base editors (CBE and ABE), proteins that enable all four types of transition mutations (C to T, T to C, A to G, and G to A) to be efficiently and cleanly installed or corrected at target positions in genomic DNA without making double-strand DNA breaks (Komor et al. Nature 2016; Gaudelli et al. Nature 2017). We also engineered a novel double-strand DNA deaminase discovered by Joseph Mougous’s lab into a mitochondrial base editor, enabling the first precision edits in the mitochondrial DNA of living cells (Mok et al. Nature 2020). Base editing has been used by laboratories around the world in a wide range of organisms and cell types. By integrating base editors with in vivo delivery strategies, we have addressed animal models of human genetic diseases such as progeria, with phenotypic rescue and lifespan extension. I will also describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit (Anzalone et al. Nature 2019). We performed >175 edits in human cells including targeted insertions, deletions, and all 12 types of point mutations without requiring double-strand breaks or donor DNA templates. We applied prime editing in human cells to correct efficiently and with few byproducts the primary genetic causes of sickle cell disease (requiring a transversion in HBB) and Tay-Sachs disease (requiring a deletion in HEXA), to install a protective transversion in PRNP, and to precisely insert various tags and epitopes into target loci. Four human cell lines and primary post-mitotic mouse cortical neurons support prime editing with varying efficiencies. Prime editing offers efficiency and product purity advantages over HDR, complementary strengths and weaknesses compared to base editing, and lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Prime editing further expands the scope and capabilities of genome editing.
Dr. Douglas Densmore (Boston University) to present CSB seminar on Thursday, November 5, 2020 at 2:00pm via Zoom
"Genetic Circuits, Cloud Labs, and COVID-19"
Synthetic biology is the process of forward engineering living systems. These systems can be used to produce bio-based materials, agriculture, medicine, and energy. One approach to designing these systems is to employ techniques from the design of embedded electronics. These techniques include abstraction, standards, and formal models. Together these form the foundation of “bio-design automation”, where software, robotics, and microfluidic devices combine to create exciting biological systems of the future. In this talk, I will discuss three general topics. The first is how software tools can be created to act as “genetic compilers” that transform high-level specifications into engineered “genetic circuits”. The second topic is how these genetic circuits can be automatically communicated to both local and community “cloud labs” where robotics, assembly-line style automation, and formalized protocol descriptions can be employed to safely and efficiently manufacture these systems. Finally, I will conclude with how these two elements have combined to power the BU Clinical Testing Laboratory where over 5000 COVID-19 tests are performed daily.
Dr. Hiroaki Suga (University of Tokyo) to present CSB seminar on Wednesday, October 21, 2020 at 6:00pm via Zoom
"Genetic Code Reprogramming That Revolutionizes The Discovery Processes Of Peptide Drug Leads"
Macrocyclic peptides possess a number of pharmacological characteristics distinct from other well-established therapeutic molecular classes, resulting in a versatile drug modality with a unique profile of advantages. Macrocyclic peptides are accessible by not only chemical synthesis but also ribosomal synthesis. Particularly, recent inventions of the genetic code reprogramming integrated with an in vitro display format, referred to as RaPID (Random non-standard Peptides Integrated Discovery) system, have enabled us to screen mass libraries (>1 trillion members) of non-standard peptides containing multiple non-proteinogenic amino acids, giving unique properties of peptides distinct from conventional peptides, e.g. greater proteolytic stability, higher affinity (low nM to sub nM dissociation constants similar to antibodies), and superior pharmacokinetics. The field is rapidly growing evidenced by increasing interests from industrial sectors, including small start-ups as well as mega-pharmas, toward drug development efforts on macrocyclic peptides, which has led to several de novo discovered peptides entering clinical trials. This lecture discusses the aforementioned screening technology involving the method of “genetic code reprogramming” powered by flexizymes, and several showcases of therapeutic potentials of macrocyclic peptides.
Dr. Chang Liu (UC Irvine) to present CSB seminar on Friday, October 25, 2019 at 3:00pm in Tech M345
“Synthetic Genetic Systems for Rapid Mutation and Evolution in vivo"
We are interested in building genetic systems that have extremely high mutation rates in order to speed up the evolution of target proteins and enzymes in vivo as well as to record transient information, such as lineage relationships or exposure to biological stimuli, as durable genetic information in situ. I will primarily discuss our work on building OrthoRep, a highly error-prone orthogonal DNA replication system that mutates user-selected genes at a rate of 1e-5 substitutions per base (s.p.b.) without any increase in the genomic mutation rate (1e-10 s.p.b). This ~100,000-fold mutational acceleration allows for the rapid continuous evolution of target biomolecules entirely in vivo using a simple serial passaging process amenable to extensive repetition. I will discuss the application of OrthoRep in exploring drug resistance, studying protein evolution, and evolving useful enzymes and proteins. I will also comment on the value of scalable continuous evolution in searching for and understanding old and new biomolecular function going forward.
Dr. Adam Arkin (UC Berkeley) to present CSB seminar on Friday, May 24, 2019 at 4:00pm in Tech L361
“Creation of engineered and synthetic microbial assemblages for understanding and application”
If one wishes to deploy an organism in the environment or a plant/animal host one must take into account both the challenges and power in the microbial consortia that inevitably preexist in these locations. Here we will discuss dissection and assembly of natural and artificial consortia of microbes and phage and their possible engineering for various applications.
Dr. Ron Weiss (MIT) to present CSB seminar on Friday, April 27, 2018 at 3:00pm in Tech M345
“Mammalian Synthetic Biology: Foundation and Therapeutic Applications”
Recent advances in mammalian synthetic biology are revolutionizing how we approach long-standing problems in medicine and healthcare. Towards this goal, we are creating a toolkit for regulating gene expression in mammalian cells and employing it for a variety of applications. In this talk, we will describe synthetic developmental programs to create organoids and multi-input genetic circuits that precisely distinguish between tumor and non-tumor cells with therapeutic outcomes against cancer.
CSB and GeneMods, the NU Synthetic Biology Club, Host FBI WMD Chicago Coordinator to Discuss Biosecurity
CSB and GeneMods hosted FBI special agent Scott Mahloch to present on synthetic biology and on contemporary issues in national security. While at NU, Mahloch also met with the iGEM team, organizers of the GeneMods podcast, and members of a Chicago community bio lab startup to discuss how to continue conducting cutting edge synthetic biology research in a way that is safe and aligned with national security and safety priorities.
SynBio Seminar Series: "Synthetic Biology for Synthetic Chemistry" by Prof. Jay Keasling, Department of Chemical Engineering & Bioengineering, UC Berkeley, Synthetic Biology Department, Physical Biosciences Division, Lawrence Berkeley National Laboratory, Joint BioEnergy Institute.
Microbial metabolism can be harnessed to convert sugars and other carbonaceous feedstocks into a variety of chemicals (commodity and specialty), fuels, and pharmaceuticals. We have engineered the industrial platform microorganisms Escherichia coli and Saccharomyces cerevisiae, and are developing others like Streptomyces venezuelae, to produce a variety of molecules, including active pharmaceutical ingredients, advanced biofuels, and chemicals that might otherwise be produced from petroleum. Unlike ethanol, the advanced biofuels have the full fuel value of petroleum-based biofuels, will be transportable using existing infrastructure, and can be used in existing automobiles and airplanes. Similarly, the microbially sourced chemicals can be dropped into existing processes used to produce existing materials. These chemicals will be produced from natural biosynthetic pathways that exist in plants and a variety of microorganisms as well as from pathways that have no representation in the natural world. In addition to creating the pathways for their synthesis, we have developed means to regulate the pathways inside the host organism, including biosensors to sense intermediates or final products. Large-scale production of these chemicals and fuels will reduce our dependence on petroleum and reduce the amount of carbon dioxide released into the atmosphere, while allowing us to take advantage of our current transportation infrastructure and products supply chains.
SynBio Seminar Series: "How to Build A Genome" by Prof. Jef Boeke, Institute for Systems Genetics at NYU Langone Medical Center
March 3, 2107: 11am - 12pm, Tech LR4
Rapid advances in DNA synthesis techniques have made it possible to engineer diverse genomic elements, pathways, and whole genomes, providing new insights into design and analysis of systems. The synthetic yeast genome project, Sc2.0 is well on its way with six of the first synthetic Saccharomyces cerevisiae chromosomes completed. Undergraduate students provide a workforce for synthesis and assembly for some of these chromosomes, though a wide variety of assembly schemes are employed by the various groups building chromosomes. The synthetic genome features several systemic modifications, including TAG/TAA stop-codon swaps, deletion of subtelomeric regions, introns, tRNA genes, transposons and silent mating loci. As well, strategically placed loxPsym sites enable genome restructuring using an inducible evolution system termed SCRaMbLE (Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution). SCRaMbLE can be used as a novel method of mutagenesis, capable of generating millions of variants leading to complex genotypes and a variety of phenotypes. The fully synthetic yeast genome opens the door to a new type of combinatorial genetics based on variations in gene content and copy number, rather than base changes. We also describe supernumerary designer “neochromosomes” that add new functionalities to cells such as humanized pathways and complexes, and general approaches to engineering of karyotype. Finally, we have automated many steps in our big DNA synthesis pipeline, opening the door to massively parallel big DNA assembly.
SynBio Seminar Series: "Biological Design for Health & the Environment" by Prof. Pamela A Silver, Department of Systems Biology, Harvard University
January 20, 2017: 11:00am - 12:00pm, Tech LR4
The engineering of Biology presents infinite opportunities for therapeutic design, diagnosis, prevention of disease and solutions to environmental problems. We use what we know from Nature to engineer systems with predictable behaviors. We also seek to discover new natural strategies to then re-engineer. This ‘Synthetic Biology’ has deep practical and social consequences for both basic and applied research. Here, I will present concepts and experiments that address how we approach these problems in a systematic way.
We engineer components of the gut microbiome to act as both diagnostics and therapeutics. In doing so, we have been able to explore the inflamed gut. We can engineer the same bacteria to secrete toxins that could result in localized killing of pathogens and to act in a communal manner.
All cells use compartmentalization of proteins to enhance biochemical reactions. We have discovered a wide spread strategy by which all prokaryotes sequester chemical reactions to protect from toxic intermediates. These results have far-reaching implications for cell-based manufacturing and sustainability.
GeneMods Inaugural Meeting
NU Synthetic Biology Club
Monday, January 11, 2016
12:00 PM - 1:00 PM
Cook Hall 3118
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