Design principles for synthetic gene regulation: understanding how cis-regulatory functions are encoded in plant DNA

Lead Research Organisation: University of East Anglia
Department Name: Graduate Office

Abstract

Plants are emerging as commercially-relevant production systems for high-value natural products. This requires suites of non-homologous, characterised regulatory elements for applications such as balancing components within a responsive circuit and preventing the build-up of toxic intermediates along a biosynthesis pathway. Plant regulatory sequences are comprised of complex arrangements of protein binding motifs and cis-regulatory elements. Both the primary DNA sequence and secondary DNA structure contribute to regulating gene-expression by recruiting proteins and dictating nucleosome architecture. This project will apply an original synthetic-biology approach to study the relationship between sequence and function utilising comparative genomic approaches to inform the design of synthetic regulatory sequences. This will enable us to understand how cis-regulatory function is encoded in specific DNA sequences. The project will focus on the identification and characterisation of cis-regulatory elements conserved across plants to inform the design of minimal synthetic elements that function across species. Comparative analysis of genome sequences will be used to inform iterative 'design-build-test-learn' cycles in which the function of libraries of designed, synthetic sequences will be analysed. The student will be trained in bioinformatics and comparative genomics analyses, synthetic biology approaches and low and high-throughput plant molecular biology and biotechnology techniques.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 30/09/2015 29/09/2023
2116919 Studentship BB/M011216/1 30/09/2018 31/12/2022 Samuel Witham
 
Description Background:
Nitrate (N) is essential for plant growth and metabolic processes. The use of N-containing fertilisers helped to improve crop yield over several decades but had negative impacts on the environment. In response to changes in N availability, plants have been shown to alter the expression of thousands of genes. Previous work has indicated that these changes are coordinated by a complex network of transcription factors (TFs).

Achievements to date:
Using a combination of in vitro and in planta assays, we have investigated numerous interactions within a key nitrogen response gene regulatory network in Arabidopsis thaliana, characterising physical interactions and quantifying regulatory consequences. Our results indicate the presence of a key feed-forward loop and help to elucidate the phenotypes (e.g. root architecture, plant yield) observed in loss-of-function mutations.
Exploitation Route A molecular understanding of transcriptional regulation of N-responses in Arabidopsis and its conservation in crop species provides a model for engineering plant N-responses using gene editing and network rewiring. These techniques could eventually be used to engineer crops with improved nitrogen-use efficiency, reducing dependency on nitrogen fertilisers.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology

 
Description UEA i-Teams 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact I worked in a multidisciplinary team of PhD students for 12 weeks to advise inventors on commercialising their product. Through this I gained intellectual property, communication and networking training and also worked with an industry mentor. I attended workshops and presentations by entrepreneurs and industry experts, and I presented our research and recommendations to colleagues, business leaders and employers.
Year(s) Of Engagement Activity 2019
URL https://www.uea.ac.uk/business/access-entrepreneurship-and-innovation/i-teams