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Seminar Series

Upcoming Events

Dr. Stanley Qi (Stanford University) to present CSB seminar on Tuesday, April 20, 2021 at 1:00pm via Zoom

 

Dr. Elizabeth Sattely (Stanford University) to present CSB seminar on Thursday, May 4, 2021 at 1:00pm via Zoom

 

Past Events

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. 

Prof. Jay Keasling

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.

Jef Boeke Seminar

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. 

Dr. Pamela Silver

GeneMods Inaugural Meeting

NU Synthetic Biology Club

Monday, January 11, 2016
12:00 PM - 1:00 PM
Cook Hall 3118
Learn more about this event

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