New preprint: Developing, characterizing and modeling CRISPR-based point-of-use pathogen diagnostics

We’re excited to share our recent work developing a nucleic acid sequence-based amplification pathogen diagnostic for SARS-CoV-2, with 20-200 aM sensitivity. We also develop an explanatory model to gain mechanistic insight into reaction performance. Congratulations to Katie, Dr. Kate Dray, and our wonderful collaborators in the Lucks, Jewett, and Mangan groups. Check out the preprint here!

New paper: HaloTag display enables quantitative single-particle characterisation and functionalisation of engineered extracellular vesicles

We’re excited to announce our recent work developing a method using flexible HaloTag labeling to absolutely quantify surface protein loading at the individual EV level, providing new insights into EV heterogeneity. An interesting new insight is that existing methods can substantially underestimate surface display. Congratulations to Dr. Roxi Mitrut, Dr. Devin Stranford, and Beth. Check out the paper here!

New paper: Genetically encoding multiple functionalities into extracellular vesicles for the targeted delivery of biologics to T cells

We’re very excited to share our latest work, now published in Nature Biomedical Engineering! Here, we introduce the GEMINI platform for engineering multifunctional extracellular vesicles as versatile, programmable, biological delivery vehicles. Congratulations to Dr. Devin Stranford and Beth. Check out the paper here and check out a press article about the paper here!

New preprint: HaloTag display enables quantitative single-particle characterization and functionalization of engineered extracellular vesicles

We’re excited to announce our recent work developing a method using flexible HaloTag labeling to absolutely quantify surface protein loading at the individual EV level, providing new insights into EV heterogeneity. An interesting new insight is that existing methods can substantially underestimate surface display. Congratulations to Roxi and Devin. Check out the preprint here!

New paper: Comparative evaluation of synthetic cytokines for enhancing production and performance of NK92 cell-based therapies

We’re excited to share our latest work focused on evaluating synthetic cytokines to enhance the production and performance of promising off-the-shelf cell therapies for treating cancer. We engineered natural killer-like NK92 cells to express six synthetic cytokines and evaluated their utility for driving expansion, cancer cell killing, and resistance to tumor microenvironmental conditions. Congratulations to Simrita, Patrick, Roxi, and Iva. Check out the paper here!

New paper: Mapping CAR T-cell design space using agent-based model

We’re excited to announce our latest work, now published in Frontiers in Molecular Biosciences! Through a collaboration with the Bagheri lab, we developed an agent-based computational testbed to explore how tunable CAR T-cell features and tumor properties impact solid tumor treatment. We adapted the Bagheri lab’s ARCADE framework to develop CAR T-cell Agent-based Representation of Cells And Dynamic Environments (CARCADE). This model enables one to explore how changing key tumor/treatment features impacts therapeutic efficacy, yielding hypotheses that correspond to various experimental equivalents. In this study, we validate the model, interrogate the biological underpinnings of various treatment outcomes, and propose novel tuned treatment strategies that can be tested experimentally. Congratulations to Alex and our excellent collaborators Dr. Jessica Yu and Dr. Neda Bagheri of the Bagheri lab! Check out the paper here, and access the CARCADE code freely on GitHub here!

New preprint: Bioengineering multifunctional extracellular vesicles for targeted delivery of biologics to T cells

We’re very excited to share our recent EV engineering work, now on bioRxiv! Here, we introduce the GEMINI platform for engineering multifunctional extracellular vesicles as programmable biological delivery vehicles. We demonstrate EV targeting, cargo loading, and fusion capabilities by delivering Cas9-sgRNA complexes to primary human T cells to knock out an HIV co-receptor. Check out the preprint here!

New paper: Elucidating Design Principles for Engineering Cell-Derived Vesicles to Inhibit SARS-CoV-2 Infection

We’re excited to share that our study investigating nanoscale decoys as SARS-CoV-2 inhibitors is out in Small! We learned that engineered decoy nanoparticles are potent viral inhibitors and appear quite resistant to viral evolutionary escape. We hope that the design rules and performance metrics we identified will accelerate the development and preclinical evaluation of this exciting new class of antiviral therapeutics. Congratulations to Taylor, Devin, and Roxi and our excellent collaborator Dr. Neha Kamat. Check out the paper here! Additionally, check out some press about the paper here!

 

New review article: The evolution of synthetic receptor systems

We’re thrilled to announce the publication of a review in which we survey the existing mammalian synthetic biology toolkit of protein-based receptors and signal-processing components, highlighting efforts to evolve and integrate some of the foundational synthetic receptor systems. This is the review we wish existed, so we wrote it ourselves! Congratulations to Hailey, and our excellent collaborators Janvie and Dr. Leonardo Morsut. Check out the paper here!

New paper: GAMES: A dynamic model development workflow for rigorous characterization of synthetic genetic systems.

We’re thrilled to announce the publication of GAMES, a model development workflow for rigorous characterization of synthetic genetic systems. Congratulations to Kate and Joe, and our excellent collaborators Dr. Niall Mangan and Dr. Neda Bagheri. We hope that GAMES will be useful for synthetic and systems biology researchers interested in systematic, reproducible dynamic model development. Check out the paper here!

New preprint: Elucidating design principles for engineering cell-derived vesicles to inhibit SARS-CoV-2 infection

We’re excited to introduce our work demonstrating that biologics called “decoy” vesicles can inhibit SARS-CoV-2 infection and are robust to multiple problematic viral mutations. Congratulations to Taylor and Devin, and our excellent collaborator Dr. Neha Kamat. We hope that the engineering insights identified in this study will accelerate the development of this exciting new class of antiviral therapeutics (for COVID-19 and/or other diseases). Check out the preprint here!

New preprint: GAMES: A dynamic model development workflow for rigorous characterization of synthetic genetic systems.

We’re thrilled to introduce GAMES, a model development workflow for rigorous characterization of synthetic genetic systems. Congratulations to Kate and Joe, and our excellent collaborators Dr. Niall Mangan and Dr. Neda Bagheri. We hope that GAMES will be useful for synthetic and systems biology researchers interested in systematic, reproducible dynamic model development. Check out the preprint here!

New Paper: Model-guided design of mammalian genetic programs is out in Science Advances

We’re excited to announce that our new study on predictive design of mammalian genetic programs is out in Science Advances! We paired engineered genetic parts that have special capabilities with computational models to design circuits that perform sophisticated, useful functions. We’re excited because this where synthetic biology is increasingly going: transitioning from construction based upon biophysical intuition to using predictive computational models to guide design of biological functions. Our approach enabled us to build a whole bunch of circuits executing digital logic and analog signal processing, integrating different mechanisms, and which worked as predicted at surprisingly high levels of complexity. We also showed how these circuits can be linked to other synthetic biology parts, including MESA biosensors, to build cells that sense and process environmental information in customized ways. Congrats to Joe, Viswajit, Amy, Patrick, Jon, and collaborator Dr. Neda Bagheri on this exciting work! Check out the new paper here! Additionally, check out the Northwestern Now press piece on the study here!

New paper: Computation-guided optimization of split protein systems is out in Nature Chemical Biology

We’re excited that SPORT, a computational protein design strategy for adjusting reconstitution propensity to fall into the sweet spot for your application, has officially been released in Nature Chemical Biology today. This Rosetta-based pipeline identifies mutations that tweak reconstitution propensity so that a split protein comes together only when needed – a property that is useful for creating protein-based sensors, biochemical assays, and parts for synthetic biology. Congratulations to Taylor, Jon, Will, Elizabeth, Alex, and our excellent and key collaborators Srivatsan Raman and Tony Meger on this fantastic effort! Check out our new paper here! Additionally, check out some press from Northwestern Engineering on the study here!

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New paper: Elucidation and refinement of synthetic receptor mechanisms is out in Synthetic Biology

We are thrilled to announce our paper synthetic receptor mechanisms is out in Synthetic Biology today! In this study,  took a deep dive into Modular Extracellular Sensor Architecture (MESA) design, identified several handles for substantially improving performance, and applied these findings to build next-gen receptors. We hope that these insights will help guide the use of MESA receptors for many applications and may also inform the design and refinement of other synthetic receptors. Congrats to Hailey, Patrick, Joe, Anthony, Taylor, Lauren, Everett, and Amy! Check out our paper here!

New preprint: Computation-guided optimization of split protein systems

We’re thrilled to introduce SPORT, a computational protein design strategy for adjusting reconstitution propensity to fall into the sweet spot for your application. Congratulations to Taylor, Jon, Will, Elizabeth, Alex, and our excellent and key collaborators Srivatsan Raman and Tony Meger. This exciting and collaborative work involved a lot of hard work on both the experimental and computational efforts, and is an exciting step in split protein optimization for a wide array of applications! Check out our preprint here!

Center for Synthetic Biology Faculty work with Artist-at-Large Dario Robleto to think about how their research affects society and are featured in a video about the collaboration

Dario Robleto returns to Northwestern as the new Artist-at-Large, working with faculty all over campus to discuss the implications of their research on society and ethics. Several professors in the Center for Synthetic Biology, including Josh Leonard, Danielle Tullman-Ercek, and Julius Lucks, are featured in a video about the collaboration.

To learn more about this exciting, and thought provoking collaboration, check out the video here!

New pre-print: the COMET mammalian synthetic biology toolkit

We’re thrilled to share a new toolkit for mammalian synthetic biology: the COMET library of synthetic transcription factors, promoters, and accompanying models. Congratulations to Patrick, Joseph, Joe and Hailey and our key collaborator Neda Bagheri! This is true tour-de-force many years in the making, and we’re excited to share this with the community! Check out our preprint here, and follow some twitter discussion here.

 

Congrats to recent graduates!

Suchitra, Daniel, Austin, Joseph, and Amy all graduated this year with a masters!

Brandon, Vis, and Parth graduate from undergraduate programs, and Vis and Parth continue on to medical school!

Good luck to all in the next phase of their lives! We will miss you!

Josh Leonard participates in interdisciplinary ethics panel at The Block Museum of Art

The Block Museum of Art hosted “Exploring Ethics: Across Art, Humanities, and Science”, a public event that provided researchers in various fields and artists a platform to share their experiences in encountering, raising, and answering new ethical questions as well as engage with the public on these topics. The event featured Northwestern synthetic biologists Danielle Tullman-Ercek, Julius Lucks, and Josh Leonard, as well as Artist-at-Large Dario Robleto and professor of medical education and anthropology Megan Crowley Matoka. Discussions ranged from capturing the ethics of science as art to engage two separate fields and the public, how to best get research to the point of need, and the cultural and ethical impact of organ transplant donation.

See the press release about the event here.

Copyright @SeanSuPhoto |@PurplePhotoCo.

Northwestern hosts 6th International Mammalian Synthetic Biology Workshop

The conference took place from May 17th-19th on Northwestern University’s campus and brought in researchers from around the world with over 150 in attendance. The first ever pre-conference workshop tutorial series took place on Friday, May 17th, providing an open forum for those new to and experienced in mammalian synthetic biology to ask questions to experts about topics such as sensing, cell signaling and differentiation, gene expression, and protein engineering, with professors Julius Lucks, Leonardo Morsut, Tara Deans, and Danielle Tullman-Ercek leading the discussions. Saturday and Sunday featured talks from experts in mammalian synthetic biology such as Linda Griffith, Melody Swartz, Ron Weiss, Martin Fussenegger, and many more. Leonard Lab member Devin Stranford gave a talk on her extracellular vesicle research and its applications to treating HIV. Additionally, Leonard Lab members Joe Muldoon, Taylor Dolberg, Patrick Donahue, Alex Prybutok, Kate Dray, Joseph Draut, Brandon Lim, Vis Kandula, Parth Shah, and Anthony Kang presented posters at the poster session on Saturday evening. Sunday’s talks concluded with a panel discussing the broader ethical implications and impacts of synthetic biology research, featuring Artist-at-Large Dario Robleto, bioethicist Laurie Zoloth, and historians Ben Hurlbut and Gaymon Bennett. Josh was presented with a commemorative plaque for helping organize and host the conference, which will take place by the Centre for Synthetic and Systems Biology at the University of Edinburgh, Scotland.

See the full press release about the conference here.

 

Vis receives top award at Stanford Undergraduate Research Conference

Congratulations to Vis Kandula, who received the “Outstanding Presenter” award at this year’s Stanford Undergraduate Research Conference, which took place from April 5-7. Of the 400 participants that applied from around North America, 80 individuals were accepted to present their research projects ranging from topics about experimental life sciences to quantitative social sciences. Vis was selected as an Outstanding Presenter in the experimental life sciences category.

 

Nature Chemical Biology publishes a News & Views article about Kelly’s NCB Paper

Synthetic biology: Sensing with modular receptors 
Matthew Brenner, Jang Hwan Cho and Wilson W Wong
doi:10.1038/nchembio.2290
Sensing and responding to diverse extracellular signals is a crucial aspect of cellular decision-making that is currently lacking in the synthetic biology toolkit. The development of modular receptor platforms allows for the rewiring of cellular input-output relationships.

Honor

Congratulations to Andrew Younger for being selected for the Best Mentor Award from Niles West High School

Honor

Congratulations to Michelle Hung for being awarded the Excellence in Research Award from the American Society of Cell and Gene Therapy

Science Fair Results!

Niles West High School students, mentored by Andrew Younger, get invited to the Illinois State Science fair and the Intel International Science and Engineering fair in Los Angeles. Good Luck!