Dr C.K Schmidt
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
University of Manchester Supervisors: Dr Christine Schmidt, Jim Warwicker. A*STAR Supervisor: Frank Eisenhaber (BII).
Posttranslational modification with ubiquitin is fundamental to most aspects of eukaryotic cell biology. This importance translates to human health, as defective ubiquitin networks are linked to diseases including cancer, neuro-degeneration and immunodeficiency. Ubiquitin can be modified itself, leading to different ubiquitin topologies, col-lectively termed the ubiquitin code. Ubiquitin-modified substrates are recognised by specific receptors that translate the modifications into biochemical and cellular events, for instance to promote genome stability through the DNA damage response. Many thousands of ubiquitylation sites have been revealed. By contrast, only few receptors spe-cific to different ubiquitin topologies are known. This drastically limits our ability for translating the ubiquitin code.
To address this challenge, the project will make use of novel comprehensive approaches to systematically define the proteomes binding to different ubiquitin topologies. The project integrates computational as well as biophysical, cellular and biochemical assays that will be combined to unique pipelines to identify novel ubiquitin-binding regions that will impact on multiple cell biology areas. Moreover, the work will provide the means for studying underexplored networks of other ubiquitin and ubiquitin-like topologies. Based on the cross-disciplinary techniques of this project, the work will lay the foundation for new areas of ubiquitin biology. Moreover, in the longer run, the findings have potential to aid the design of new therapeutic strategies to treat diseases associated with perturbed ubiquitin net-works.
The successful candidate will have a first-class degree in biology, bioinformatics or any associated sciences, and an eagerness to cross the boundaries of traditional academic disciplines, especially between biology and computational sciences. Knowledge of a scripting language, such as Pearl and/or Python, will be advantageous but not essential.
Schmidt website: https://www.research.manchester.ac.uk/portal/christine.schmidt.html
Eisenhaber website: http://www.bii.a-star.edu.sg/research/biography/franke.php
Funding Notes
This project is available to UK/EU candidates. Funding covers fees (UK/EU rate) and stipend for four years. Overseas candidates can apply providing they can pay the difference in fees and are from an eligible country. Candidates will be required to split their time between Manchester and Singapore, as outlined on www.manchester.ac.uk/singaporeastar.
Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
References
1. C. K. Schmidt et al., Systematic E2 screening reveals a UBE2D–RNF138–CtIP axis promoting DNA repair. Nat. Cell Biol. 17, 1458–1470 (2015).
2. P. A. Knobel et al., USP28 is recruited to sites of DNA damage by the tandem BRCT domains of 53BP1 but plays a minor role in double-strand break metabolism. Mol. Cell. Biol. 34, 2062–74 (2014).
3. B. Eisenhaber et al., The Recipe for Protein Sequence-Based Function Prediction and Its Implementation in the ANNOTATOR Software Environment. Methods Mol. Biol. 1415, 477–506 (2016). (F. Eisenhaber is last author on this paper).
4. W. A. Sherman et al., HPMV: Human protein mutation viewer — relating sequence mutations to protein sequence architecture and function changes. J. Bioinform. Comput. Biol. 13, 1550028 (2015). (F. Eisenhaber is last author on this paper).
5. W. Xi et al., Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes. ACS Nano. 10, 5835–5846 (2016). (C. Schmidt is co-corresponding author on this paper).
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