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Synthetic biology: designing reliable and predictable gene circuits in mammalian cells

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  • Full or part time
    Dr Daniel Hebenstreit
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Synthetic biology holds great promise for many diverse fields, including energy and food production and the enhancement of human health. A major aim of synthetic biology is it to construct artificial gene circuits that function reliably and that can be tailored to different applications. Currently this is not possible due to fluctuations and random variations on the molecular level. Systems based on more than four or five regulatory interactions usually become unpredictable.

In this project, we will use genome editing in order to rewire signaling pathways in a mammalian cell line. We will restrict variations in the general states of the cells [1, 2] in order to design more complex synthetic gene circuits that are robust and predictable.

The project will initially involve transient transfections of the HEK293 cell line to ectopically express factors and explore their suitability for our project. The results will be evaluated using a combination of single-molecule RNA-FISH [3], flow cytometry, and next generation sequencing. In later project stages, CRISPR/Cas9 technology [4] will be employed to re-engineer the cell lines to yield stable systems with controllable synthetic components.



Keywords: Synthetic biology, systems biology, gene expression, transcription, stochastic kinetics, biological noise, genome editing, mammalian cells

Funding Notes

The University’s standard entry requirements are as follows:
• You must hold at least a upper second class UK honours degree (2:1) or equivalent qualification
• 2 satisfactory academic references
• Submit an English Language test certificate e.g IELTS (if appropriate)
Please note:
It is a requirement that overseas students will show that their ability to understand and express themselves in both written and spoken English is sufficiently high for them to derive the full benefit from the PhD. Please note that the requirement for admission is IELTS 6.5 (with no component below 6.0) or equivalent.

References

1. Paulsson, J., Physics of Life Reviews, 2005. 2(2): p. 157-175. 

2. Swain, P.S., M.B. Elowitz, and E.D. Siggia, Proc Natl Acad Sci U S A, 2002. 99(20): p. 12795-800. 

3. Raj, A., et al., Nat Methods, 2008. 5(10): p. 877-9. 

4. Ran, F.A., et al., Nat Protoc, 2013. 8(11): p. 2281-308. 


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