Caleb Bashor uses approaches in synthetic biology to understand how complex behavior emerges from the properties of components that comprise cellular regulatory networks. His research focus is on engineering synthetic regulatory programs capable of reshaping cellular phenotype, with an eye on developing transformational cell-based therapeutics from engineered human cells.
The Bashor Lab utilizes diverse eukaryotic cell types (mammalian immune and stem cells) to learn how to reprogram the complex regulatory circuitry involved in cellular sense and response. His approach uses theory and modelling to guide circuit design, and incorporates DNA assembly, microfluidics, and next-generation sequencing to build and characterize circuit libraries in high-throughput.
As a postdoctoral research fellow in the laboratory of Professor James Collins at MIT’s IMES, Bashor established foundational strategies for the comprehensive, bottom-up construction of synthetic regulatory systems in eukaryotes, focusing on the synthesis of both transcriptional (gene networks) and post-translational (signaling pathways) circuits. Both of these platforms will be brought to bear on his circuit engineering efforts.
Synthetic biology: Engineering synthetic regulatory circuitry, with a focus on mammalian gene and signal transduction circuits. Foundational techniques for constructing stable circuit expression in diverse mammalian cell types. Building circuits that can sense, compute, and respond to the extracellular environment. Using massively parallel circuit construction to rapidly and comprehensively explore circuit design space.
Systems biology: Understanding how biological behavior arises from network structure. Using synthetic rewiring to explore the design logic of signaling networks. Developing new approaches for studying and modeling signaling at the single-cell level using high-throughput perturbation and analysis.
Translation: Harnessing mammalian synthetic biology to create cell-based therapeutics. Engineering synthetic circuitry for delivery to adoptive cells. Using synthetic regulatory programs to guide stem cell reprogramming and differentiation. Using synthetic sense and response circuitry to reprogram immune cell function.
Heins, Z.J., Mancuso, C.P., Kiriakov, S., Wong, B.G., Bashor, C.J.*, Khalil, A.S*. Designing Automated, High-throughput, Continuous Cell Growth Experiments Using eVOLVER. J. Vis. Exp. (147), e59652, doi:10.3791/59652 (2019).
O'Connell RW, Bashor CJ (2019) The least mating pathway: Synthetically refactoring a familiar signaling system for new applications. Cell, 177: 521-3
Bashor CJ*, Patel N*, Choubey S, Beyzavi A, Kondev J, Collins JJ, Khalil AS (2019) Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies. Science, 364(6440): 593-7
*Perspective by Andrew H. Ng and Hana El-Samad in Science, 363(6440): 531-2
Brandon G Wong, Christopher P Mancuso, Szilvia Kiriakov, Caleb J Bashor#, Ahmad S Khalil# (2018) Precise, automated control of conditions for high-throughput growth of yeast and bacteria with eVOLVER. Nature Biotechnology, doi:10.1038/nbt.4151
Gordley RM, William RE, Bashor CJ, Toettcher JE, Yan S, Lim WA (2016) Engineering dynamical control of cell fate switching using phspho regulons. PNAS, available online.
Chan CC*, Lee JW*, Cameron DE, Bashor CJ, Collins JJ (2015) ‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial containment. Nature Chemical Biology, 12: 82-6
Keung AJ, Bashor CJ, Kirikov, S, Collins JJ, Khalil AS (2014) Using targeted chromatin regulators to engineer combinatorial and spatial transcriptional regulation. Cell, 158: 110-120
Cameron DE*, Bashor CJ*, Collins JJ (2014) A brief history of synthetic biology. Nature Reviews Microbiology, 12: 381-90
Khalil AS*, Lu TK*, Bashor CJ*, Ramirez CL, Pyenson NC, Joung JK, Collins JJ (2012) A synthetic biology framework for programming eukaryotic transcription functions. Cell, 150: 647-58
Bashor CJ, Collins JJ (2012) Insulating gene circuits from context by RNA processing. Nature Biotechnology, 30: 1061-2
Bashor CJ, Horowitz AA, Peisajovich SG, Lim WA (2010) Rewiring cells: synthetic biology as a tool to interrogate the organization of living systems. Annual Review of Biophysics, 39: 515-37
Bashor CJ, Helman NC, Yan S, Lim WA (2008) Using engineered scaffolds to reshape MAP kinase pathway signaling dynamics. Science, 319: 515-37