Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Towards high-throughput single cell growth optimization and production analysis using picoliter bioreactors

Grünberger A, Probst C, Wiechert W, Kohlheyer D. Towards high-throughput single cell growth optimization and production analysis using picoliter bioreactors. Presented at the Metabolic Engineering IX 2012, Biarritz, France

Immuntherapie der allergischen Rhinitis ohne Allergene? : Neue Möglichkeiten einer Immunmodulation durch Vakzinierung mittels „virus-like particles“ und CpG-Motiven

BACKGROUND: Allergen-specific immunotherapy is generally accepted as the only causal therapy for allergic rhinitis. Up to now there has been a dogma in immunotherapy for inhalation allergies that at least allergen components are necessary for effective therapy. This dogma could, however, be swayed by current results of effective immunotherapy without allergens. Virus-like particles (VLP) represent a novel and interesting aspect for immunotherapy for inhalation allergies. AIM: Initial experiences with successful immunotherapy without allergens are available. This article describes the currently available clinical experiences with bacteriophage VLPs filled with oligonucleotides which contain CpG motifs with tumor antigens on the surface for the treatment of allergic rhinitis. RESULTS: Vaccination with VLPs was found to be well tolerated, immunogenic and effective for prophylactic treatment of various infections. Bacteriophage VLPs filled with CpG motifs with tumor antigens on the surface led clinically to an induction of specific T-cells in tumor patients and were successfully implemented as adjuvants during prophylactic vaccinations. CONCLUSION: The VLP technique in combination with the use of CpG motifs could contribute to the causal treatment of complex diseases, such as malignancies, autoimmune diseases and allergies