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Background:
Genetic control challenges in both fundamental biology and biotechnology are effectively tackled by building functionally separated (orthogonal) systems within one cell. A key example is the use of the phage T7 RNA polymerase, which allows us to: (a) specifically regulate a synthetic gene, (b) minimise a circuit’s impact on cellular resources and growth, and even (c) engineer transcriptional control systems regulated by light.
Analogously, orthogonal ribosomes allow us to introduce a second pool of ribosomes into cells without interfering with cellular functions. Indeed, we have shown that this enables us to engineer the orthogonal subpool by insertion of Broccoli RNA, for fluorescent labelling and in vivo ribosome tracking and quantification. However, we lack the tools to specifically control their activity, other than by controlling the synthesis rate of the ribosomal RNA. As ribosome biogenesis is slow, we cannot programme this system to respond quickly to external cues. A system that allowed us to control subpool activity directly without requiring ribosome biogenesis would constitute a model platform to study ribosome activity in living cells, as well as to build next generation microbial cell factories.
Aim and objectives:
This project aims to build an orthogonal ribosome control system to allow for reversible ribosome activity control. The student will use bioinformatic analyses and create libraries of candidate control proteins, screening for activity with high throughput microbial assays. They will create libraries for protein engineering and develop positive and negative selection strategies for developing orthogonal controls by directed evolution. Finally, they will use a range of biophysical and molecular techniques (polysome and ribosome profiling, binding assays) to characterise the systems they have engineered.
The student will benefit from the excellent research environment in the School of Molecular and Cellular Biology at Leeds, as well as membership of the research networks of the Astbury Centre, LeedsOmics and the Leeds Engineering Biology community.
Lab websites and links:
https://biologicalsciences.leeds.ac.uk/homepage/84/school-of-molecular-and-cellular-biology
For informal enquiries about the project, please contact Dr Eszter Csibra e.csibra@leeds.ac.uk.
About YBDTP:
YBDTP brings together world-class bioscience research and innovation, as well as excellence in doctoral supervision, across the region. YBDTP will fund postgraduate researchers at the Universities of Leeds, Sheffield, York, Bradford, Hull, Leeds Beckett, Sheffield Hallam and Teesside forming a strong regional training partnership. In YBDTP you'll benefit from a regional doctoral training programme that has interdisciplinary collaboration at its core. The aim is to enable you to develop a range of research skills in biological, biotechnology and biochemical areas as well as equip you with core data analysis and professional skills that are necessary for bioscience research and related non-academic careers.
https://www.whiterose-mechanisticbiology-dtp.ac.uk/yorkshire-bioscience-dtp/
Funding Notes:
Funding: A tax-free annual stipend at the standard UKRI rate (£19,237 for 2024/25 entry), research costs and tuition fees at UK rate
Academic year: 2025/26
Open to: International (including EU) and UK (home) students
Eligibility:
Open to International (including EU) and UK (home) students.
You can apply if you have, or are expecting to gain, at least an upper second-class honours degree or equivalent. Due to the interdisciplinary nature of this programme, we welcome applications if your background is in any biological, chemical or physical science or mathematics and are interested in using your skills in addressing biological questions. International students should check if they meet the entry requirements for their country.
We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international (EU and non-EU) applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
The Yorkshire Bioscience DTP is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Not all projects will be funded; a limited number of candidates will be appointed via a competitive process.
English language: If English isn't your first language, you may need to provide evidence of your English language ability.
How to apply:
Application deadline: 5pm, Friday 14th March 2025
To submit your application, click on the link to the Expression of Interest form in the Funding Notes section of any of your chosen projects. You can apply for up to 3 YBDTP projects (which can be at different universities).
We would advise you to read the questions in the form before submitting your application. Inside the form there is a link to a document for you to see the questions in advance.
If you have any questions about the application process, please email wrdtp@leeds.ac.uk.
If you have any questions about the project you are interested in, please email the project supervisor (details inside the project description).
How we allocate:
Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly. If you're shortlisted, you'll be invited for an interview on a date to be confirmed in February 2025. You'll be notified as soon as possible after the interview dates whether your application has been successful, placed on a reserve list or unsuccessful. If you are successful, you'll be required to confirm your intention to accept the studentship within 10 days.
Terms and conditions:
The studentships are fully funded for four years, and you must complete your PhD in four years.
You'll receive the UKRI minimum doctoral stipend per year for your living costs, which is paid to you in regular instalments. The UK Research and Innovation (UKRI) stipend is tax free and does not need to be paid back.
International students will need to have sufficient funds to cover the costs of their student visa, NHS health surcharge, travel insurance and travel to the UK as these are excluded from UKRI funding.
To apply for a studentship from the Yorkshire Bioscience Doctoral Training Partnership to undertake this project, please complete an expression of interest form for October 2025 recruitment here: View Website
Research output data provided by the Research Excellence Framework (REF)
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