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Revealing DNA’s Secret Structures with Ruthenium: From the Test Tube, to the Cell (FIELDENJ_U21SCIEP)


School of Chemistry

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Dr J Fielden , Dr R Lord No more applications being accepted Competition Funded PhD Project (Students Worldwide)
Norwich United Kingdom Biochemistry Inorganic Chemistry Physical Chemistry Synthetic Chemistry

About the Project

There is a lot more to DNA than the Watson-Crick double helix. As a flexible polymer, it folds in different ways adopting many different secondary structures.(i) Much less is known about these structures – how and when they form, what they do and how their structure relates to their role. Even so, such “alternative” structures have been linked to switch on/off of genes, and thus genetic diseases such as diabetes and cancer. 

 

This PhD focuses on one such structure, the i-Motif (iM). Existence of iM in organisms was proven in 2018,(ii) but little is known about its biological structure/function relationships, and research is held back by a lack of effective detection methods that can be applied to live cells and organisms. However, we recently discovered a ruthenium complex that can, in vitro, detect iM in the presence of other DNA forms through a phosphorescence lifetime increase,(iii) and is likely compatible with living systems. The goal of this studentship is to improve our lead compound, increasing the strength and specificity of its response, improve our understanding of its phosphorescence switch on, and begin the work of translating this research from the test tube to cells. As such, the project, led by Dr John Fielden, is highly interdisciplinary. It will involve training in a wide range of techniques, from synthesis of new ligands and complexes, to characterisation of their interaction with DNA and their effect in cells, and involves both internal and external collaborations.  

 

Informal enquiries are welcomed and should be directed to Dr John Fielden.  

For more information on the supervisor for this project, please go here https://people.uea.ac.uk/john_fielden

The programme type is PhD

Start date of project is 1st October 2021

The mode of study is full time

Studentship length is 3.5 years NB. 3.5 year studentships have a (non-funded) 6 month ‘registration only’ period 


Funding Notes

Successful candidates who meet UKRI’s eligibility criteria will be awarded an EPSRC funded studentship covering fees, stipend (£15,285 p.a., 2020-21), and research funding for 3.5 years. International applicants (EU/non-EU) are eligible for fully-funded EPSRC studentships. The eligibility requirements are detailed in the UKRI Training Grant Guidance: https://www.ukri.org/wp-content/uploads/2020/10/UKRI-291020-guidance-to-training-grant-terms-and-conditions.pdf
Entry requirements are 2:1 in Chemistry. Chemical Physics, Pharmacy or Biochemistry may be acceptable given adequate synthetic chemistry training.

References

(i) M. L. Bochman, K. Paeschke, V. A. Zakian, Nature Rev. Genet. 2012, 13, 770.
(ii) M. Zeraati, D. B. Langley, P. Schofield, A. L. Moye, R. Rouet, W. E. Hughes, T. M. Bryan, M. E. Dinger, D. Christ, Nature Chem. 2018, 10, 631.
(iii) P. Spence, J. Fielden, Z. Waller, J. Am. Chem. Soc. 2020, 142, 13856.
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