Class revision exercise - Synthetic Genomics

A series of papers has been published in Science (10th March 2017), which provide a picture of current progress to resynthesise the entire genome of Saccharomyces cerevisiae - the SC2.0 project (http://syntheticyeast.org/sc2-0/)

Four of these papers have been chosen for review, and they cover a range of challenges that have been found with the design, construction, testing and properties of synthetic chromosomes.

Students should enlist themselves into four groups to tackle each of these papers. Each group should plan to present a summary of their paper within around 15 minutes, to leave time for questions. A total of 30 minutes will be allocated for discussion of each paper.
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Synthetic yeast genome

Paper 1 - Rules for design of a synthetic genome
Design of a synthetic yeast genome.
Richardson, S. M., Mitchell, L. A., Stracquadanio, G., Yang, K., Dymond, J. S., DiCarlo, J. E., … Bader, J. S. (2017). Science, 355(6329), 1040–1044. http://doi.org/10.1126/science.aaf4557

Paper 2 - Debugging a synthetic chromosome
Bug mapping and fitness testing of chemically synthesized chromosome X.
Wu, Y., Li, B.-Z., Zhao, M., Mitchell, L. A., Xie, Z.-X., Lin, Q.-H., … Yuan, Y.-J. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf4706

Paper 3 - Engineering rDNA loci
Engineering the ribosomal DNA in a megabase synthetic chromosome.
Zhang, W., Zhao, G., Luo, Z., Lin, Y., Wang, L., Guo, Y., … Dai, J. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf3981

Paper 4 - 3D conformation of synthetic chromosomes
3D organization of synthetic and scrambled chromosomes
Mercy, G., Mozziconacci, J., Scolari, V. F., Yang, K., Zhao, G., Thierry, A., … Koszul, R. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf4597



Additional articles:

Designer Eukaryotic Chromosome.
Annaluru, N., Muller, H., Mitchell, L. A., Ramalingam, S., Stracquadanio, G., Richardson, S. M., … Han, J. S. (2014). Science (New York, N.Y.), 344(April), 55–59. http://doi.org/10.1126/science.1249252

Synthesis, debugging, and effects of synthetic chromosome consolidation: synVI and beyond.
Mitchell, L. A., Wang, A., Stracquadanio, G., Kuang, Z., Wang, X., Yang, K., … Boeke, J. D. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf4831

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.
Shen, Y., Wang, Y., Chen, T., Gao, F., Gong, J., Abramczyk, D., … Yang, H. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf4791

"Perfect" designer chromosome V and behavior of a ring derivative.
Xie, Z.-X., Li, B.-Z., Mitchell, L. A., Wu, Y., Qi, X., Jin, Z., … Yuan, Y.-J. (2017). Science, 355(6329). http://doi.org/10.1126/science.aaf4704

Genome-scale engineering for systems and synthetic biology.
Esvelt, K. M., & Wang, H. H. (2013). Molecular Systems Biology, 9(641), 641. http://doi.org/10.1038/msb.2012.66