Ahmad Khalil - Academia.edu (original) (raw)
Papers by Ahmad Khalil
Nature Biotechnology, 2009
The engineering of mechanical, electrical and chemical systems is enabled by well-established fra... more The engineering of mechanical, electrical and chemical systems is enabled by well-established frameworks for handling complexity, reliable means of probing and manipulating system states and the use of testing platforms-tools that are largely lacking in the engineering of biology. Developing properly functioning biological circuits can involve complicated protocols for DNA construction, rudimentary modelguided and rational design, and repeated rounds of trial and error followed by fine-tuning. Limitations in characterizing kinetic processes and interactions between synthetic components and other unknown constituents in vivo make troubleshooting and modeling frustrating and prohibitively time consuming. As a result, the design cycle for engineering synthetic gene networks remains slow and error prone.
NATURE REVIEWS GENETICS, 2010
The circuit-like connectivity of biological parts and their ability to collectively process logic... more The circuit-like connectivity of biological parts and their ability to collectively process logical operations was first appreciated nearly 50 years ago 1 . This inspired attempts to describe biological regulation schemes with mathematical models 2-5 and to apply electrical circuit analogies to biological pathways 6,7 . Meanwhile, breakthroughs in genomic research and genetic engineering (for example, recombinant DNA technology) were supplying the inventory and methods necessary to physically construct and assemble biomolecular parts. As a result, synthetic biology was born with the broad goal of engineering or 'wiring' biological circuitry -be it genetic, protein, viral, pathway or genomic -for manifesting logical forms of cellular control. Synthetic biology, equipped with the engineering-driven approaches of modularization, rationalization and modelling, has progressed rapidly and generated an ever-increasing suite of genetic devices and biological modules.
Cell, Jan 3, 2014
The transcription of genomic information in eukaryotes is regulated in large part by chromatin. H... more The transcription of genomic information in eukaryotes is regulated in large part by chromatin. How a diverse array of chromatin regulator (CR) proteins with different functions and genomic localization patterns coordinates chromatin activity to control transcription remains unclear. Here, we take a synthetic biology approach to decipher the complexity of chromatin regulation by studying emergent transcriptional behaviors from engineered combinatorial, spatial, and temporal patterns of individual CRs. We fuse 223 yeast CRs to programmable zinc finger proteins. Site-specific and combinatorial recruitment of CRs to distinct intralocus locations reveals a range of transcriptional logic and behaviors, including synergistic activation, long-range and spatial regulation, and gene expression memory. Comparing these transcriptional behaviors with annotated CR complex and function terms provides design principles for the engineering of transcriptional regulation. This work presents a bottom-...
Nature reviews. Genetics, 2015
As synthetic biology approaches are extended to diverse applications throughout medicine, biotech... more As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication.
Nature Biotechnology, 2009
The engineering of mechanical, electrical and chemical systems is enabled by well-established fra... more The engineering of mechanical, electrical and chemical systems is enabled by well-established frameworks for handling complexity, reliable means of probing and manipulating system states and the use of testing platforms-tools that are largely lacking in the engineering of biology. Developing properly functioning biological circuits can involve complicated protocols for DNA construction, rudimentary modelguided and rational design, and repeated rounds of trial and error followed by fine-tuning. Limitations in characterizing kinetic processes and interactions between synthetic components and other unknown constituents in vivo make troubleshooting and modeling frustrating and prohibitively time consuming. As a result, the design cycle for engineering synthetic gene networks remains slow and error prone.
NATURE REVIEWS GENETICS, 2010
The circuit-like connectivity of biological parts and their ability to collectively process logic... more The circuit-like connectivity of biological parts and their ability to collectively process logical operations was first appreciated nearly 50 years ago 1 . This inspired attempts to describe biological regulation schemes with mathematical models 2-5 and to apply electrical circuit analogies to biological pathways 6,7 . Meanwhile, breakthroughs in genomic research and genetic engineering (for example, recombinant DNA technology) were supplying the inventory and methods necessary to physically construct and assemble biomolecular parts. As a result, synthetic biology was born with the broad goal of engineering or 'wiring' biological circuitry -be it genetic, protein, viral, pathway or genomic -for manifesting logical forms of cellular control. Synthetic biology, equipped with the engineering-driven approaches of modularization, rationalization and modelling, has progressed rapidly and generated an ever-increasing suite of genetic devices and biological modules.
Cell, Jan 3, 2014
The transcription of genomic information in eukaryotes is regulated in large part by chromatin. H... more The transcription of genomic information in eukaryotes is regulated in large part by chromatin. How a diverse array of chromatin regulator (CR) proteins with different functions and genomic localization patterns coordinates chromatin activity to control transcription remains unclear. Here, we take a synthetic biology approach to decipher the complexity of chromatin regulation by studying emergent transcriptional behaviors from engineered combinatorial, spatial, and temporal patterns of individual CRs. We fuse 223 yeast CRs to programmable zinc finger proteins. Site-specific and combinatorial recruitment of CRs to distinct intralocus locations reveals a range of transcriptional logic and behaviors, including synergistic activation, long-range and spatial regulation, and gene expression memory. Comparing these transcriptional behaviors with annotated CR complex and function terms provides design principles for the engineering of transcriptional regulation. This work presents a bottom-...
Nature reviews. Genetics, 2015
As synthetic biology approaches are extended to diverse applications throughout medicine, biotech... more As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication.