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  Understanding how intrinsic disorder drives auxin receptor complex formation


   Faculty of Biological Sciences

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  Prof Stefan Kepinski, Dr Anastasia Zhuravleva  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Intrinsically disordered protein regions lack stable structure and instead move stochastically through an ensemble of conformations. Where it was once thought that absence of structure meant absence of function, it is now known that intrinsic disorder plays a critical role in cellular signalling systems. This project uses the co-receptor system for the plant hormone auxin as a model to understand how ordered regulation of protein function can arise from structural disorder.

Auxin is probably the most interesting molecule in biology. Via the formation of the TIR1-auxin-Aux/IAA co-receptor complex, auxin regulates virtually every aspect of plant development. The central importance of auxin for plant growth has meant that the auxin receptor complex is a high-value target for the development of auxinic herbicides meaning that understanding receptor complex formation is both an intellectually intriguing and economically important problem in structural and plant biology.

Our recent work has shown that half of the Aux/IAA protein component, including the motif that interacts with the F-box protein TIR1, is largely intrinsically disordered but contains regions of transient cryptic structure. We have also shown that the conformational ambiguity of the Aux/IAA is central to this process of complex formation. This project would allow you to build of these exciting discoveries using a combination of NMR, SPR, Cryo-EM and molecular dynamics simulation approaches and receive truly interdisciplinary training in an exciting and rapidly developing field. The project is a collaboration between researchers at Leeds and Prof. Richard Napier (University of Warwick - Biophysics) and Dr Charo Del Genio (University of Coventry - Structural Modelling and molecular dynamics simulation).

Eligibility

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject area. A Master degree is desirable but not essential.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are: • British Council IELTS - score of 6.0 overall, with no element less than 5.5 • TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable).

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert
  • For source of funding please state you are applying for a Gosden PhD scholarship
Biological Sciences (4)

Funding Notes

This Gosden funded scholarship will attract an annual tax-free stipend of £15,609 for up to 4 years, subject to satisfactory progress and will cover the UK tuition fees. Due to limited funding we can only consider applicants for this position who are eligible to pay academic fees at the UK fee rate.

References

1. Kuhn, A., Ramans Harborough, S., McLaughlin, H.M., Natarajan, B., Verstraeten, I., Friml, J., Kepinski, S., Østergaard, L. (2020) Direct ETTIN-auxin interaction controls chromatin states in gynoecium development. eLife 9:e51787 DOI: 10.7554/eLife.51787
2. Wieteska, L., Shahidi, S., Zhuravleva A. (2017) Allosteric fine-tuning of the conformational equilibrium poises the chaperone BiP for post-translational regulation. eLife;6:e29430.
3. Ramans Harborough, S, Kalverda, A.P., Thompson, G.S., Kieffer, M., Kubes, M., Quareshy, M., Prusinska, J., Hayashi, K., Napier, R.M., Manfield, I.M., Kepinski, S. (2019) A fuzzy encounter complex precedes formation of the fully-engaged TIR1-Aux/IAA auxin co-receptor system. bioRxiv doi: https://doi.org/10.1101/781922

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