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4-year PhD Studentship in Synthetic Biology for the Rational Reprogramming of Living Cells


Project Description

The ability to reprogram living cells would open up opportunities to repurpose biology and tackle major challenges covering the sustainable production of material to the development of living therapeutics [1]. However, at present the reprogramming of cells is difficult because we do not fully understand the rules for how new functionalities are best implemented [2, 3].

In computer software engineering, “design patterns” provide reusable solutions to frequently encountered problems that are independent of the programming language used for implementation. This PhD will explore whether biology also exploits its own form of design patterns in gene regulatory networks to control key cellular behaviours. Focusing on the role of small regulatory motifs that are known to be enriched in living systems, and which cluster in specific ways [4], we will use computational methods to study the cellular functions that motifs support and their robustness to being used in different ways. These biological design rules will then be tested by developing a new gene regulatory system based on CRISPR/Cas technologies, to allow for the construction of our own large-scale regulatory circuits in living cells. The student will use this capability to explore the ability to synthesise novel regulatory programs from motif-based design rules tackling a broad range of core functionalities (e.g. complex decision making and dynamic oscillations in gene expression). Insight from this work will fuel exciting new approaches for constructing synthetic biological programs that go far beyond what is currently achievable, while also providing a deeper understanding of the fundamental ways that biology harnesses the substrate of life to process information.

The project will be based in the Biocompute Lab (www.biocomputelab.org) at the University of Bristol. All research will be performed in close collaboration with Dr Boyan Yordanov and Dr Sara-Jane Dunn from the Biological Computation Group at Microsoft Research Cambridge (https://www.microsoft.com/en-us/research/group/biological-computation/). The student will carry out regular research visits between these groups and gain experience of academic and industrial research environments. The highly interdisciplinary nature of the project also means that we expect the student to be open to learning complementary experimental or computational skills depending upon their background.

ELIGIBILITY
First class or upper second-class honours degree in a related topic (e.g. biology, biochemistry, chemistry, physics, engineering or computer science). The candidate needs to meet RCUK residency requirements (https://epsrc.ukri.org/skills/students/help/eligibility/): either 1. a home UK student, or 2. an EC national who has lived in the UK for 3 years prior to starting the PhD (and if the 3 years have been spent in higher education, then they have to have been resident in the EEA or Switzerland immediately before this).

APPLICATION PROCESS
Deadline for applications: 30/11/2019 (early applications are advised).
Please contact the supervisor Dr Thomas Gorochowski () with a short CV and cover letter explaining your motivation. Interviews will be held early in December and it is hoped that a successful candidate can start as soon as possible in the new year (before September 2020).

Funding Notes

The funding covers tuition, a tax-free stipend, plus a travel/consumables budget for 4 years.

References

1. "Living computers powered by biochemistry", The Biochemist 41, 14-18, 2019.
https://doi.org/10.1042/BIO04103014

2. “Genetic circuit characterization and debugging using RNA-seq”, Molecular Systems Biology 13, 952, 2017.
http://msb.embopress.org/content/13/11/952

3. “Registry in a tube: multiplexed pools of retrievable parts for genetic design space exploration”, Nucleic Acids Research 45, 1553-1565, 2017.
http://nar.oxfordjournals.org/content/early/2016/12/21/nar.gkw1226.full

4. "Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks", Science Advances 4, eaap9751, 2018.
http://advances.sciencemag.org/content/4/3/eaap9751


How good is research at University of Bristol in Biological Sciences?

FTE Category A staff submitted: 64.60

Research output data provided by the Research Excellence Framework (REF)

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