Synthetic biology will transform how we grow food, what we eat, and where we source materials and medicines. Here I have selected six products that are now on the market, highlighting the underlying ...technologies and projecting forward to the future that can be expected over the next ten years.
Fluid deformable surfaces Voigt, A.
Journal of fluid mechanics,
11/2019, Volume:
878
Journal Article
Peer reviewed
Open access
Lipid membranes are examples of fluid deformable surfaces, which can be viewed as two-dimensional viscous fluids with bending elasticity. With this solid–fluid duality any shape change contributes to ...tangential flow and
vice versa
any tangential flow on a curved surface induces shape deformations. This tight coupling between shape and flow makes curvature a natural element of the governing equations. The modelling and numerical tools outlined in Torres-Sánchez
et al.
(
J. Fluid Mech.
, vol. 872, 2019, pp. 218–271) open a new field of study by enabling the exploration of the role of curvature in this context.
Plants are exposed to a wide range of potential pathogens, which derive from diverse phyla. Therefore, plants have developed successful defense mechanisms during co-evolution with different ...pathogens. Besides many specialized defense mechanisms, the plant cell wall represents a first line of defense. It is actively reinforced through the deposition of cell wall appositions, so-called papillae, at sites of interaction with intruding microbial pathogens. The papilla is a complex structure that is formed between the plasma membrane and the inside of the plant cell wall. Even though the specific biochemical composition of papillae can vary between different plant species, some classes of compounds are commonly found which include phenolics, reactive oxygen species, cell wall proteins, and cell wall polymers. Among these polymers, the (1,3)-β-glucan callose is one of the most abundant and ubiquitous components. Whereas the function of most compounds could be directly linked with cell wall reinforcement or an anti-microbial effect, the role of callose has remained unclear. An evaluation of recent studies revealed that the timing of the different papilla-forming transport processes is a key factor for successful plant defense.
Bacterial genes associated with a single trait are often grouped in a contiguous unit of the genome known as a gene cluster. It is difficult to genetically manipulate many gene clusters because of ...complex, redundant, and integrated host regulation. We have developed a systematic approach to completely specify the genetics of a gene cluster by rebuilding it from the bottom up using only synthetic, well-characterized parts. This process removes all native regulation, including that which is undiscovered. First, all noncoding DNA, regulatory proteins, and nonessential genes are removed. The codons of essential genes are changed to create a DNA sequence as divergent as possible from the wild-type (WT) gene. Recoded genes are computationally scanned to eliminate internal regulation. They are organized into operons and placed under the control of synthetic parts (promoters, ribosome binding sites, and terminators) that are functionally separated by spacer parts. Finally, a controller consisting of genetic sensors and circuits regulates the conditions and dynamics of gene expression. We applied this approach to an agriculturally relevant gene cluster from Klebsiella oxytoca encoding the nitrogen fixation pathway for converting atmospheric N2 to ammonia. The native gene cluster consists of 20 genes in seven operons and is encoded in 23.5 kb of DNA. We constructed a "refactored" gene cluster that shares little DNA sequence identity with WT and for which the function of every genetic part is defined. This work demonstrates the potential for synthetic biology tools to rewrite the genetics encoding complex biological functions to facilitate access, engineering, and transferability.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these ...natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology--including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits--and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UL, UM, UPUK
Microbial engineering often requires fine control over protein expression-for example, to connect genetic circuits or control flux through a metabolic pathway. To circumvent the need for trial and ...error optimization, we developed a predictive method for designing synthetic ribosome binding sites, enabling a rational control over the protein expression level. Experimental validation of >100 predictions in Escherichia coli showed that the method is accurate to within a factor of 2.3 over a range of 100,000-fold. The design method also correctly predicted that reusing identical ribosome binding site sequences in different genetic contexts can result in different protein expression levels. We demonstrate the method's utility by rationally optimizing protein expression to connect a genetic sensor to a synthetic circuit. The proposed forward engineering approach should accelerate the construction and systematic optimization of large genetic systems.
Coordinated cellular movements are key processes in tissue morphogenesis. Using a cell-based modeling approach we study the dynamics of epithelial layers lining surfaces with constant and varying ...curvature. We demonstrate that extrinsic curvature effects can explain the alignment of cell elongation with the principal directions of curvature. Together with specific self-propulsion mechanisms and cell-cell interactions this effect gets enhanced and can explain observed large-scale, persistent, and circumferential rotation on cylindrical surfaces. On toroidal surfaces the resulting curvature coupling is an interplay of intrinsic and extrinsic curvature effects. These findings unveil the role of curvature and postulate its importance for tissue morphogenesis.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Computation can be performed in living cells by DNA-encoded circuits that process sensory information and control biological functions. Their construction is time-intensive, requiring manual part ...assembly and balancing of regulator expression. We describe a design environment, Cello, in which a user writes Verilog code that is automatically transformed into a DNA sequence. Algorithms build a circuit diagram, assign and connect gates, and simulate performance. Reliable circuit design requires the insulation of gates from genetic context, so that they function identically when used in different circuits. We used Cello to design 60 circuits forEscherichia coli(880,000 base pairs of DNA), for which each DNA sequence was built as predicted by the software with no additional tuning. Of these, 45 circuits performed correctly in every output state (up to 10 regulators and 55 parts), and across all circuits 92% of the output states functioned as predicted. Design automation simplifies the incorporation of genetic circuits into biotechnology projects that require decision-making, control, sensing, or spatial organization.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Computation underlies the organization of cells into higher-order structures, for example during development or the spatial association of bacteria in a biofilm. Each cell performs a simple ...computational operation, but when combined with cell-cell communication, intricate patterns emerge. Here we study this process by combining a simple genetic circuit with quorum sensing to produce more complex computations in space. We construct a simple NOR logic gate in Escherichia coli by arranging two tandem promoters that function as inputs to drive the transcription of a repressor. The repressor inactivates a promoter that serves as the output. Individual colonies of E. coli carry the same NOR gate, but the inputs and outputs are wired to different orthogonal quorum-sensing 'sender' and 'receiver' devices. The quorum molecules form the wires between gates. By arranging the colonies in different spatial configurations, all possible two-input gates are produced, including the difficult XOR and EQUALS functions. The response is strong and robust, with 5- to >300-fold changes between the 'on' and 'off' states. This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between cells.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Once an engineered organism completes its task, it is useful to degrade the associated DNA to reduce environmental release and protect intellectual property. Here we present a genetically encoded ...device (DNAi) that responds to a transcriptional input and degrades user-defined DNA. This enables engineered regions to be obscured when the cell enters a new environment. DNAi is based on type-IE CRISPR biochemistry and a synthetic CRISPR array defines the DNA target(s). When the input is on, plasmid DNA is degraded 10(8)-fold. When the genome is targeted, this causes cell death, reducing viable cells by a factor of 10(8). Further, the CRISPR nuclease can direct degradation to specific genomic regions (for example, engineered or inserted DNA), which could be used to complicate recovery and sequencing efforts. DNAi can be stably carried in an engineered organism, with no impact on cell growth, plasmid stability or DNAi inducibility even after passaging for >2 months.
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