![Page 1: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/1.jpg)
Synthetic biology
June Gorrochategui Ortega
Genomics
![Page 2: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/2.jpg)
Introduction
Bottom-up approaches
Top-down approaches
Semi-synthetic approaches
Conclusion
Synthetic biology
![Page 3: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/3.jpg)
Introduction
Definition: design and construction of biological devices and systems
Types
1. DNA-based device construction
2. Genome-driven cell engineering
3. Protocell creation
Bottom-up
Top-down
Semi-synthetic
![Page 4: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/4.jpg)
Bottom-up approaches
Simple systems are put toghether, to create more complex systems
– Constructtion from basic units of
• whole genomes
• cells
![Page 5: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/5.jpg)
Bottom-up: genome synthesis
Short nucleotide sequences are constructed and assembledD. G. Gibson, et al. Complete Chemical Synthesis, Assembly, and Cloning of a
Mycoplasma genitalium Genome. Science 319, 1215 (2008)
Partition of a wild M. genitalium genome into 101 cassettes
Synthesis of 50bp oligonucleotides
and assembling
Assembling of5-7 kb
sequences: 101 cassettes
obtained
Five step assembling and
transplantation into yeast
![Page 6: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/6.jpg)
Bottom-up: protocell creation
Protocell:
– hypothetical precursor structures of the first cells
– Cell-like construct
Two options to create protocells:
Using basic units such as nucleotides and amino acids
(bottom-up)
Using more complex units such as DNA and enzymes
(semi-synthetic)
![Page 7: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/7.jpg)
Introduction
Bottom-up approaches
Top-down approaches
Semi-synthetic approaches
Conclusion
Synthetic biology
![Page 8: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/8.jpg)
Top-down approaches
Start from a living organism TOP
Try to make it as simple as possible DOWNMINIMAL CELL
MINIMAL GENOME
Bioinformatics approach
Experimental approach
![Page 9: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/9.jpg)
Bioinformatics approach
Compare different genomes:
– Genes in common → Minimal genome
First used by Mushegian and Koonin in 1996
Compared the three fully sequenced bacterial genomes available at the time (Haemophilus influenzae, M. genitalium and Escherichia coli)
![Page 10: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/10.jpg)
Experimental techniques
Knocking out of genes to see if they are essential for the cell
Some examples:
Global transposon mutagenesis Antisense RNA
![Page 11: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/11.jpg)
Introduction
Bottom-up approaches
Top-down approaches
Semi-synthetic approaches
Conclusion
Synthetic biology
![Page 12: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/12.jpg)
Semi-synthetic approach
Introduce biomolecules into a synthetic compartment
Autopoiesis (self-producing) is needed
AUTOPOIESIS
Theory that describes the behavior of all biological systems
It defines the characteristics a synthetic biosystem must have in order to mimic
a natural one
![Page 13: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/13.jpg)
Minimal autopoietic system
A and B: components of the environment
S and M: components of the cell
Y and W: waste material
The system is a self-bounded molecular assembly
Its dynamics are:
![Page 14: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/14.jpg)
Semi-synthetic minimal cell
Essential genetic and metabolic compounds are
introduced inside vesicles or liposomes
![Page 15: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/15.jpg)
Conclusion
Aplications
Synthetic systhems capable of detecting dangerous substances
Synthetic communication systems that coordinate cellular response
Improvement in tissue and organ engineering
Synthetic biology is becoming a very important field
Improve our understanding of biology
Give solutions for global problems
![Page 16: The future of Synthetic Biology - Curso de Genética - …genetica.uab.cat/base/documents/Genomics/June...Semi-synthetic approach Introduce biomolecules into a synthetic compartment](https://reader031.vdocuments.us/reader031/viewer/2022022013/5b34cdb27f8b9aec518c962e/html5/thumbnails/16.jpg)
References
Luisi PL, Ferri F, Stano P. Approaches to semi-synthetic minimal cells: a review. Naturwissenschaften 93: 1-13. (2006)
Fritz B. R. , Timmerman L. E. , Daringer N. M. , Leonard J. N. and Jewett M. C. Biology by Design: From Top to Bottomand Back. Journal of Biomedicine and Biotechnology. doi:10.1155/2010/232016 (2010)
D. G. Gibson, et al. Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science 319, 1215 (2008)
Hutchinson CA, Peterson SN, Gill SR, Cline RT, White O, Fraser CM, Smith HO, Venter JC. Global transposon mutagenesis and a minimal Mycoplasma genome. Science 286: 2165–2169 (1999)
Chen YY, et al.: Synthetic biology: advancing biological frontiers by building synthetic systems. Genome Biology 2012, 13:240 (2010)