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In silico discovery of the degrons and the degron-mediated recruitment modules of the human Ubiquitin E3 Ligase system

  • Full or part time
    Dr N Davey
  • Application Deadline
    Sunday, January 05, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

We are recruiting a highly motivated informatician (or bio-informatician) on a 4-year PhD studentship as part of the UBIMOTIF MSCA H2020 Innovative Training Network titled “Short linear interaction motifs as specificity determinants in the ubiquitin system – discovery, mechanisms and therapeutic opportunities”. The UBIMOTIF consortium includes 13 research groups and 6 partners from 10 European countries and is a joint training and research program with focus on identification, characterisation and exploitation of short linear motifs in the ubiquitin system. Visit http://www.ubimotif.ku.dk for more information.

In humans, roughly 700 enzymes – comprising mainly writers (E3 ubiquitin ligases) and erasers (deubiquitinating enzymes (DUBs)) – control the ubiquitin modification status of protein substrates. However, how the vast majority of these enzymes select their substrates remains unknown and represents a fundamental shortcoming in our understanding of the ubiquitin system. The UBIMOTIF project will determine specificity determinants of substrate recruitment modules of the ubiquitin ligases and DUBs to identify their docking motifs and interactors. The discovery of the molecular details of motif-mediated substrate-enzyme interactions in the ubiquitin system will revolutionise our understanding of this fundamental biological processes.
The position will be hosted by the Short Linear Motif Team in the Division Of Cancer Biology at the Institute of Cancer Research, Chelsea, London.


As part of the UBIMOTIF project, the student will spend 3 months (months 24-27) in the Khmelinskii lab (Institut für Molekulare Biologie, Mainz, Germany) to integrate multiplexed protein stability (MPS) profiling data into the data analysis pipeline and 3 months (months 12-15) in the Ivarsson lab (University of Uppsala, Sweden) to design and analyse the ProP-PD experiments used to test the motif-binding pocket discovery predictions.

EXPERIENCE
One or more of the following skills are desirable (but not required):
• Proficiency in Python programming and experience with Linux
• Knowledge and experience in the analysis of large biological datasets
• Knowledge and experience with Machine Learning (e.g. SciKit-learn or TensorFlow)
• Knowledge and experience with web and database development
• Understanding and interest in evolution and biology


SPECIAL REQUIREMENTS
• Applicants can be of any nationality.
• Applicants must have an ability to understand and express themselves in both written and spoken English to a level that is sufficiently high for them to derive the full benefit from the network training.
• Applicants must be eligible to enrol in a PhD programme at the ICR.
• Being a PhD student in an ITN requires a considerable amount of travelling including participation in meetings and workshops and completion of two 3 month secondments outside the host laboratory (at the University of Uppsala, Sweden and the IMB Mainz, Germany). Therefore, a requirement is the willingness to travel and stay abroad.

Candidates will be required to meet the Marie Skłodowska-Curie Early Stage Researcher eligibility criteria:

• Mobility Rule: researchers must not have resided or carried out their main activity (work, studies, etc.) in the United Kingdom for more than 12 months in the 3 years immediately before the recruitment date. Compulsory national service, short stays such as holidays, and time spent as part of a procedure for obtaining refugee status are not taken into account. The earliest possible recruitment date is 1 March 2020.
• Early Stage Researcher (ESR) criteria: ESRs must, at the date of recruitment by the host organisation, be in the first four years (full-time equivalent research experience) of their research careers and have not been awarded a doctoral degree. Full-Time Equivalent Research Experience is measured from the date when the researcher obtained the degree entitling him/her to embark on a doctorate (either in the country in which the degree was obtained or in the country in which the researcher is recruited, even if a doctorate was never started or envisaged).
• You will only be considered for the position if you fulfil (and can prove so) the eligibility criteria.


The project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 860517”

Keywords /Subject Areas:
E3 Ubiquitin ligases
Protein Protein Interactions
Systems biology
Evolutionary Biology
Structural Biology
Bioinformatics PhD London

Funding Notes

The student will receive a mobility allowance and a family allowance (where applicable) as part of the employment package. The position is funded for four years. For the first three years, the selected candidate will receive a salary of €5,171/month consisting of a monthly living allowance of €4,571 and a monthly mobility allowance of €600. An additional €500/month is available if the participant is eligible for the family allowance. The exact salary will be calculated in GBP once the appointment has been confirmed. The 4th year of the PhD will be covered by an ICR-funded stipend at ICR rates.

References

Candidates must have a first class or upper second-class honours BSc Honours/MSc in Computer Science, Bioinformatics or similar.
For a full list of criteria see https://www.icr.ac.uk/studying-and-training/phds-for-science-graduates/phd-studentship-projects



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