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  NERC GW4+ DTP PhD project: Are some gene regulatory networks more evolvable than others?


   Department of Life Sciences

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  Prof Tiffany Taylor  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This project is one of a number that are in competition for funding from the NERC Great Western Four+ Doctoral Training Partnership (GW4+ DTP) for entry in October 2023. The GW4+ DTP consists of the Great Western Four alliance of the Universities of Bath, Bristol and Exeter and Cardiff University plus five prestigious Research Organisation partners: British Antarctic Survey, British Geological Survey, Centre for Ecology & Hydrology, the Natural History Museum and Plymouth Marine Laboratory. The partnership aims to provide a broad multi-disciplinary training, designed to produce tomorrow’s leaders in earth and environmental science.

Supervisory Team:

Lead Supervisor: Dr Tiffany Taylor, University of Bath, Life Sciences Department 

Co-Supervisor: Dr Thomas Gorochowski, University of Bristol, School of Biological Sciences

Project Background 

The difference between whether populations survive or go extinct during environmental shifts depends on whether the rate of adaptation can keep up with the rate of change. All living organisms rely on huge numbers of genes working in concert to support a variety of functions. Many of these genes are organised into networks, which can be controlled collectively. These networks have evolved a staggering complexity and can be made up of numerous interacting genes, molecular products, and regulatory elements, that together enable an organism to exquisitely respond to changes in their environment. Changes to these networks facilitate rapid adaptation because single mutations can impact many genes simultaneously. However, we don’t understand how network structures themselves evolve, and the implications that these have on an organisms’ ‘evolvability’ and ability to adapt. 

Project Aims and Methods 

This project aims to explore whether certain gene regulatory network patterns are better ‘primed’ for evolutionary rescue of a broken network compared to others. In the Taylor lab, we have observed the ability for evolution to rescue cell motility where the correct regulation of the flagella motor has been forcefully broken. This work allowed us to learn a few rules that, we believe, make some regulatory networks easier to rewire and evolve than others. Using synthetic biology to create our own regulatory networks from scratch, we can for the first time explicitly test these rules in new ways. Specifically, this project aims to generate numerous synthetic gene regulatory networks that under selection have the potential to rescue a desired phenotype. Using our ‘rulebook’, we have a priori predictions as to which network structures are best suited to this task (i.e., require the fewest mutations) and through experimental evolution, we can assess whether the rules hold more generally. This will provide deeper insight into how evolvable specific organisms and phenotypes are, the role of such rewiring to generate evolutionary innovations when new challenges are faced, and potentially harnessed to create synthetic living systems that can evolve in predictable ways. 

Using this framework, there are many potential questions that can be explored depending on the interests of the PhD student: How does strength of selection change the evolutionary outcome? What role does promiscuous binding of transcription factors play in creating opportunities for rewiring, and is there a trade-off with mis-regulation in other areas of a network? We are excited to work with the right candidate to shape the research direction with their own ideas. 

Candidate requirements 

Applicants should have a passion for a combination of evolution, molecular microbiology and/or synthetic biology. Applicants should hold, or expect to receive, a First Class or high Upper Second-Class UK Honours degree (or the equivalent qualification gained outside the UK) in a relevant subject. A master’s level qualification or additional research experience would also be advantageous.

Non-UK applicants must meet the programme’s English language requirement by 01 February 2023 (the only exemption is if you will be awarded a UK degree or degree conducted in English before your PhD start date).

Project partners  

The project will benefit from expertise in evolution of novel regulatory and genetic innovations (Taylor, Bath) and the development and evolution of artificial and synthetic biological systems (Gorochowski, Bristol). The GW4+ DTP programme will offer additional benefits including training in essential skills such as statistics, bioinformatics, and scientific writing; a supportive peer-support network spanning across four South West Universities (Bath, Bristol, Cardiff and Exeter) and collaborative partners; and outreach opportunities with the public. 

Training 

Throughout this interdisciplinary project, the student will receive extensive training in experimental evolution, synthetic biology, molecular microbiology, genetics, and bioinformatics. They will be primarily based in the Taylor lab as part of the Milner Centre for Evolution (within the Life Sciences Department) at the University of Bath with opportunities to work in the Gorochowski lab in the School of Biological Sciences at the University of Bristol. 

Enquiries and Applications:

Informal enquiries are welcomed and should be directed to Dr Tiffany Taylor [Email Address Removed]

Formal applications should be made via the University of Bath's online application form for a PhD in Biology

When completing the form, please identify your application as being for the NERC GW4+ DTP studentship competition in Section 3 Finance (question 2) and quote the project title and lead supervisor’s name in the ‘Your research interests’ section. 

More information about applying for a PhD at Bath may be found on our website.

We welcome and encourage student applications from under-represented groups. We value a diverse research environment. If you have circumstances that you feel we should be aware of that have affected your educational attainment, then please feel free to tell us about it in your application form. The best way to do this is a short paragraph at the end of your personal statement.

Project keywords: evolution, microbiology, molecular biology, synthetic biology 


Biological Sciences (4)

Funding Notes

Candidates may be considered for a NERC GW4+ DTP studentship tenable for 3.5 years. Funding covers tuition fees, a stipend (£17,668 p/a in 2022/23) and a generous allowance for research expenses and travel. Studentships are open to both Home and International students; however, International applicants should note that funding does NOT cover the cost of a student visa, healthcare surcharge and other costs of moving to the UK. In line with guidance from UK Research and Innovation (UKRI), the number of awards available to International candidates will be limited to 30% of the total.

References

Taylor, T. B., et al. (2022) Natural selection on crosstalk between gene regulatory networks facilitates bacterial adaptation to novel environments. Current Opinion in Microbiology (67) 102140
Shepherd, et al. (2022) Evolutionary innovation through transcription factor promiscuity in microbes is constrained by pre-existing gene regulatory network architecture. bioRxiv
Castle, S. D. et al. (2021). Towards an engineering theory of evolution. Nature Communications, 12(1), 1-12
Gorochowski, T. E., et al. (2018). Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks. Science Advances, 4(3)

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