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"Synthetic Biology"
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Microbial response to acid stress: mechanisms and applications
Microorganisms encounter acid stress during multiple bioprocesses. Microbial species have therefore developed a variety of resistance mechanisms. The damage caused by acidic environments is mitigated through the maintenance of pH homeostasis, cell membrane integrity and fluidity, metabolic regulation, and macromolecule repair. The acid tolerance mechanisms can be used to protect probiotics against gastric acids during the process of food intake, and can enhance the biosynthesis of organic acids. The combination of systems and synthetic biology technologies offers new and wide prospects for the industrial applications of microbial acid tolerance mechanisms. In this review, we summarize acid stress response mechanisms of microbial cells, illustrate the application of microbial acid tolerance in industry, and prospect the introduction of systems and synthetic biology to further explore the acid tolerance mechanisms and construct a microbial cell factory for valuable chemicals.
Journal Article
Mastering Complexity: Towards Bottom-up Construction of Multifunctional Eukaryotic Synthetic Cells
With the ultimate aim to construct a living cell, bottom-up synthetic biology strives to reconstitute cellular phenomena in vitro – disentangled from the complex environment of a cell. Recent work towards this ambitious goal has provided new insights into the mechanisms governing life. With the fast-growing library of functional modules for synthetic cells, their classification and integration become increasingly important. We discuss strategies to reverse-engineer and recombine functional parts for synthetic eukaryotes, mimicking the characteristics of nature’s own prototype. Particularly, we focus on large outer compartments, complex endomembrane systems with organelles, and versatile cytoskeletons as hallmarks of eukaryotic life. Moreover, we identify microfluidics and DNA nanotechnology as two technologies that can integrate these functional modules into sophisticated multifunctional synthetic cells.
Bottom-up synthetic biology thrives in reverse-engineering a particular biological function using a minimal set of molecular components, like purified proteins.
Recently, precision technologies, like microfluidics, have been used to recombine functional modules towards multifunctional synthetic cells. Synthetic biology can capitalize on a variety of pre-existing on-chip functions, which greatly increases the scope for complexity in the field.
Advances in DNA nanotechnology gave rise to a diverse range of fully synthetic functional modules, like DNA-based ion channels or motors, which can replace some protein-based parts.
Noteworthy progress has been made in achieving large and stable compartments, organelle-like multicompartment systems, and sophisticated cytoskeletal structures.
Journal Article
Engineering living therapeutics with synthetic biology
The steadfast advance of the synthetic biology field has enabled scientists to use genetically engineered cells, instead of small molecules or biologics, as the basis for the development of novel therapeutics. Cells endowed with synthetic gene circuits can control the localization, timing and dosage of therapeutic activities in response to specific disease biomarkers and thus represent a powerful new weapon in the fight against disease. Here, we conceptualize how synthetic biology approaches can be applied to programme living cells with therapeutic functions and discuss the advantages that they offer over conventional therapies in terms of flexibility, specificity and predictability, as well as challenges for their development. We present notable advances in the creation of engineered cells that harbour synthetic gene circuits capable of biological sensing and computation of signals derived from intracellular or extracellular biomarkers. We categorize and describe these developments based on the cell scaffold (human or microbial) and the site at which the engineered cell exerts its therapeutic function within its human host. The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine that holds great promise for the development of effective treatments for a wide variety of human diseases.The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine for the development of effective treatments for a variety of diseases. This article discusses advances in synthetic biology approaches to programme living cells with therapeutic functions as well as challenges for their development.
Journal Article
Regenesis : how synthetic biology will reinvent nature and ourselves
Regenesis tells of recent advances that may soon yield endless supplies of renewable energy, increased longevity and the return of long-extinct species
Book
Realizing the potential of synthetic biology
Five experts discuss their views on the main achievements and challenges of synthetic biology in basic and applied science, consider potential ethical issues, and describe how synthetic biology relates to disciplines such as systems biology and computational modelling.
Synthetic biology, despite still being in its infancy, is increasingly providing valuable information for applications in the clinic, the biotechnology industry and in basic molecular research. Both its unique potential and the challenges it presents have brought together the expertise of an eclectic group of scientists, from cell biologists to engineers. In this Viewpoint article, five experts discuss their views on the future of synthetic biology, on its main achievements in basic and applied science, and on the bioethical issues that are associated with the design of new biological systems.
Journal Article
The genesis machine : our quest to rewrite life in the age of synthetic biology
\"Synthetic biology is the promising and controversial technology platform that combines biology and artificial intelligence, opening up the potential to program biological systems much as we program computers. Synthetic biology enables us not just to read and edit DNA - the technique of CRISPR - but also write it. Rather than life being \"a beautiful game of chance\", synthetic biology creates the potential to control our genetic destiny, to say \"no\" to bad genes and build a veritable genetic app store for downloading and adding new capabilities into any cell, microbe, plant, or animal. Amy Webb and Andrew Hessel's riveting stories include: the work of scientists to develop plants that can be grown in sprawling indoor farms capable of feeding millions with a fraction of the usual resources required; a synthetic, self-regulating insulin that doesn't require injections or a pump; life-altering regenerative, personalized medicine; and novel, durable solutions to climate change. There is also whimsy, such as the dream of some geneticists to \"unextinct\" the wooly mammoth. By examining both the science and the ethical, moral, and religious issues surrounding synthetic biology, Webb and Hessel provide the background for preventing its misuse by some to re-engineer their bodies and that of their children, further increasing the disturbing division and polarization of societies into the haves (the enhanced) and the have nots. They provide the background for making wise decisions about issues such as: whether to program novel viruses to fight diseases, what genetic privacy will look like, who will \"own\" living organisms, how companies should earn revenue from engineered cells, and how to contain a synthetic organism in a lab. Whether we approve or disapprove of synthetic biology, it is coming. Now, we need to understand its promise and peril. Webb and Hessel help us understand the science as well as the political and societal issues involved\"-- Provided by publisher.
BOOK
Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity
Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic
E coli
Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine.
Synthetic biology can be used to create rationally designed living therapeutics. Here the authors engineer
E. coli
Nissle to target STING activation in antigen presenting cells for the treatment of solid tumors and demonstrate preclinical activity in murine models.
Journal Article