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Engineering synthetic ribosomal RNAs (rRNAs) in yeast


Project Description

Advances in DNA synthesis technology have led to rapid growth in the field of synthetic biology, heralding a nascent era of synthetic genomics. Sc2.0 (www.syntehticyeast.org) is an international consortium with the aim of designing and constructing a fully synthetic eukaryotic genome. Fundamental design changes to the synthetic genome include the removal of the ~1.2Mbp rDNA locus from its native locus from chromosome 12, which enable us to engineer synthetic rRNAs to understand biological fundamentals surrounding this class of RNAs.

In yeast ~150 repeats are clustered in a ~1.5 Mb repetitive region which is located on chromosome XII (chrXII). ChrXII is the largest and the rDNA locus is necessary to form the well-organized nucleolus. We have shown previously that it is possible to move the entire rDNA cluster to another chromosome. While moving the cluster to chrIII induces significant genome-wide conformational changes, there was no observable effect on fitness in standard laboratory growth conditions. Additionally, we have even eliminated the 1.5 Mb rDNA cluster in a designed 976 kb synthetic version of chromosome 12 (synXII). It is unclear, for example, whether rDNA cluster copy numbers are malleable within an evolutionary context or, for instance, if there is a strict lower limit on the number of rDNA clusters required to sustain life. The Cai lab is looking to recruit a highly motivated PhD student to undertake this exciting project.

Please see our recent publications in Science for further information (refs. 1-5, in particular #5). The student will have great opportunities to work with our international collaborators such as New York University (USA), Imperial College London (UK), EMBL (Germany) and Chinese Academy of Sciences and Beijing Genomics Institute (China).

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in life sciences or related subjects. A Masters degree in a relevant subject and/or experience in life sciences subject area/discipline synthetic biology is desirable.

A successful candidate should have a good understanding of molecular biology, biotechnology and microbiology and ideally will be familiar with research in synthetic biology, biological materials and biosynthesis. A good track record in hands-on bioscience laboratory work, especially with bacterial/yeast systems, is highly desirable. Most importantly, the applicant should be well-motivated and open-minded, able to thrive in s a multi-disciplinary research environment. The project can be tailored to the student within the research scope.

Contact for further Information:

Prof. Patrick Yizhi Cai
Email:
Website: http://www.cailab.org

Funding Notes

This is a 4 year PhD studentship funded by a Volkswagen Foundation Grant. The funding will cover tuition fees, stipend (£15,009 in 2019) and consumables.

Restricted to UK/EU applicants only.

We exect the programme to start in September 2019.

References

(1) Richardson, S. M., Mitchell, L. A., Stracquadanio, G., Yang, K., Dymond, J. S., DiCarlo, J. E., Lee, D., Huang, C. L. V., Chandrasegaran, S., Cai, Y., Boeke, J. D., and Bader, J. S. (2017) Design of a synthetic yeast genome. Science 355, 1040–1044.

(2) Schindler, D., Dai, J., and Cai, Y. (2018) Synthetic genomics: a new venture to dissect genome fundamentals and engineer new functions. Current Opinion in Chemical Biology 46, 56–62.

(3) Shen, Y., Wang, Y., Chen, T., Gao, F., Gong, J., Abramczyk, D., Walker, R., Zhao, H., Chen, S., Liu, W., Luo, Y., Müller, C. A., Paul-Dubois-Taine, A., Alver, B., Stracquadanio, G., Mitchell, L. A., Luo, Z., Fan, Y., Zhou, B., Wen, B., Tan, F., Wang, Y., Zi, J., Xie, Z., Li, B., Yang, K., Richardson, S. M., Jiang, H., French, C. E., Nieduszynski, C. A., Koszul, R., Marston, A. L., Yuan, Y., Wang, J., Bader, J. S., Dai, J., Boeke, J. D., Xu, X., Cai, Y., and Yang, H. (2017) Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome. Science 355, eaaf4791.

(4) Mercy, G., Mozziconacci, J., Scolari, V. F., Yang, K., Zhao, G., Thierry, A., Luo, Y., Mitchell, L. A., Shen, M., Shen, Y., Walker, R., Zhang, W., Wu, Y., Xie, Z.-X., Luo, Z., Cai, Y., Dai, J., Yang, H., Yuan, Y.-J., Boeke, J. D., Bader, J. S., Muller, H., and Koszul, R. (2017) 3D organization of synthetic and scrambled chromosomes. Science 355, eaaf4597.

(5) Zhang, W., Zhao, G., Luo, Z., Lin, Y., Wang, L., Guo, Y., Wang, A., Jiang, S., Jiang, Q., Gong, J., Wang, Y., Hou, S., Huang, J., Li, T., Qin, Y., Dong, J., Qin, Q., Zhang, J., Zou, X., He, X., Zhao, L., Xiao, Y., Xu, M., Cheng, E., Huang, N., Zhou, T., Shen, Y., Walker, R., Luo, Y., Kuang, Z., Mitchell, L. A., Yang, K., Richardson, S. M., Wu, Y., Li, B.-Z., Yuan, Y.-J., Yang, H., Lin, J., Chen, G.-Q., Wu, Q., Bader, J. S., Cai, Y., Boeke, J. D., and Dai, J. (2017) Engineering the ribosomal DNA in a megabase synthetic chromosome. Science 355, eaaf3981.

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