publication . Preprint . Other literature type . Article . 2020

Self-adaptive Biosystems Through Tunable Genetic Parts and Circuits

Bartoli, Vittorio; di Bernardo, Mario; Gorochowski, Thomas E.;
Open Access English
  • Published: 06 Oct 2020
  • Publisher: Preprints
Abstract
Biological systems often need to operate in complex environments where conditions can rapidly change. This is possible due to their inherent ability to sense changes and adapt their behavior in response. Here, we detail recent advances in the creation of synthetic genetic parts and circuits whose behaviors can be dynamically tuned through a variety of intra- and extra-cellular signals. We show how this capability lays the foundation for implementing control engineering schemes in living cells and allows for the creation of biological systems that are able to self-adapt, ensuring their functionality is maintained in the face of varying environmental and physiolog...
Persistent Identifiers
Subjects
free text keywords: biochemistry, biotechnology
Funded by
EC| COSY-BIO
Project
COSY-BIO
Control Engineering of Biological Systems for Reliable Synthetic Biology Applications
  • Funder: European Commission (EC)
  • Project Code: 766840
  • Funding stream: H2020 | RIA
Validated by funder
,
UKRI| EPSRC and BBSRC Centre for Doctoral Training in Synthetic Biology
Project
  • Funder: UK Research and Innovation (UKRI)
  • Project Code: EP/L016494/1
  • Funding stream: EPSRC
,
UKRI| BrisSynBio: Bristol Centre for Synthetic Biology
Project
  • Funder: UK Research and Innovation (UKRI)
  • Project Code: BB/L01386X/1
  • Funding stream: BBSRC
Communities
FET H2020FET OPEN: FET-Open research and innovation actions
FET H2020FET OPEN: Control Engineering of Biological Systems for Reliable Synthetic Biology Applications
67 references, page 1 of 5

Fernandez-Rodriguez J, Yang L, Gorochowski TE, Gordon DB, Voigt CA: Memory and Combinatorial Logic Based on DNA Inversions: Dynamics and Evolutionary Stability. ACS Synth Biol 2015, 4:1361-1372.

Sleight SC, Bartley BA, Lieviant JA, Sauro HM: Designing and engineering evolutionary robust genetic circuits. J Biol Eng 2010, 4:12. [OpenAIRE]

9. Ceroni F, Boo A, Furini S, Gorochowski TE, Borkowski O, Ladak YN, Awan AR, Gilbert C, Stan G-B, Ellis T: Burden-driven feedback control of gene expression. Nat Methods 2018, 15:387-393. •• Details the development of a feedback control system to automatically regulate the burden experienced by cells expressing a synthetic genetic construct. The major contribution is the detailed analysis of endogenous cellular responses to find a suitable burden-responsive promoter and the use of a tunable CRISPRi feedback regulatory mechanism that enables any synthetic construct to be targeted. It is shown that this system can significantly improve the yield of protein products, as well as the evolutionary stability of genetic constructs. [OpenAIRE]

10. Stanton BC, Nielsen AAK, Tamsir A, Clancy K, Peterson T, Voigt CA: Genomic mining of prokaryotic repressors for orthogonal logic gates. Nat Chem Biol 2014, 10:99-105.

11. Chappell J, Westbrook A, Verosloff M, Lucks JB: Computational design of small transcription activating RNAs for versatile and dynamic gene regulation. Nat Commun 2017, 8:1051.

12. Chappell J, Takahashi MK, Lucks JB: Creating small transcription activating RNAs. Nat Chem Biol 2015, 11:214-220.

13. Kim H, Bojar D, Fussenegger M: A CRISPR/Cas9-based central processing unit to program complex logic computation in human cells. Proc Natl Acad Sci 2019, 116:7214.

14. Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, et al.: Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation. Cell 2014, 159:647-661. [OpenAIRE]

15. Green AA, Silver PA, Collins JJ, Yin P: Toehold Switches: De-Novo-Designed Regulators of Gene Expression. Cell 2014, 159:925-939. [OpenAIRE]

16. Green AA, Kim J, Ma D, Silver PA, Collins JJ, Yin P: Complex cellular logic computation using ribocomputing devices. Nature 2017, 548:117.

17. Gorochowski TE, Chelysheva I, Eriksen M, Nair P, Pedersen S, Ignatova Z: Absolute quantification of translational regulation and burden using combined sequencing approaches. Mol Syst Biol 2019, 15:e8719.

18. Kelly CL, Harris AWK, Steel H, Hancock EJ, Heap JT, Papachristodoulou A: Synthetic negative feedback circuits using engineered small RNAs. Nucleic Acids Res 2018, 46:9875-9889.

19. Soper T, Mandin P, Majdalani N, Gottesman S, Woodson SA: Positive regulation by small RNAs and the role of Hfq. Proc Natl Acad Sci 2010, 107:9602.

20. Greco FV, Tarnowski MJ, Gorochowski TE: Living computers powered by biochemistry. The Biochemist 2019, 41:14-18.

21. Briat C, Gupta A, Khammash M: Antithetic Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks. Cell Syst 2016, 2:15-26.

67 references, page 1 of 5
Any information missing or wrong?Report an Issue