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The impact of the of structure on the spatial proteome

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  • Full or part time
    Prof Kathryn Lilley
  • Application Deadline
    Applications accepted all year round

Project Description

Prof. Kathryn Lilley, Department of Biochemistry, University of Cambridge
Prof. Anne Willis, MRC Toxicology Unit, Leicester University (re-locating to Cambridge in 2018)

It is now widely acknowledged that many proteins exist in multiple locations within a cell. In different locations, proteins may have different post translational modifications, make new sets of interactions with alternative binding partners and adopt different structures. The reasons why proteins traffic to multiple locations in turn may be influenced by the above, but also by alternative splicing and localised translation.

The aims of research in the supervisors’ labs are to define where translation of mRNA takes place in the cell, how this is regulated by protein binding partners and sequence motifs and how this changes upon cellular perturbation.
In this project, which will be based in Cambridge, the PhD candidate will carry out crucial experiments aimed at determining the relationship between the transcriptome, the spatial proteome and structure and how this changes upon cell perturbation, such as stress.
The project will involve the use of different protein extraction methods, and characterisation of peptides generated from the cell lysates by cutting edge quantitative and structural proteomics methods and informatics tools. The project will involve interaction with Cambridge and Leicester based members of the research groups and presentation of data.

The student will learn quantitative mass spectrometry, protein chemistry, protein cross linking, tissue culture, cell imaging, and next generation sequencing, plus familiarization with several programming languages and basic statistical skills.


The project will fit at the core of the group research activity of both the Lilley and Willis groups. The student will be supported and assisted by other members of these groups, including bioinformaticians, cell biologists and proteomics experts.

This project fits into the category of World Class Underpinning Bioscience/New Ways of Working

Learning outcomes and skills acquired (maximum 100 words)
The student will become familiar with the field of cell biology, translation , proteomics and mass spectrometry.

The skills acquired will be cell culture, basic protein biochemistry, next generation DNA sequencing, mass spectrometry, quantitative proteomics approaches and cross-linking methods, bioinformatics and data interpretation.

The student will also be expected to give a talk about their short project and will be given training in presentation skills, both oral and written.

The student will be working in two vibrant research groups and will be given the opportunity to work as part of large teams of PhD students and post doctoral research workers.

References

1. A draft map of the mouse pluripotent stem cell spatial proteome Christoforou A, Mulvey CM, Breckels LM, Geladaki A, Hurrell T Hayward PC, Naake T, Gatto L, Viner R, Martinez Arias A and Lilley KS (2016) Nature Communications 12;7:9992. doi: 10.1038/ncomms9992
2. Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics., Breckels LM, Holden SB, Wojnar D, Mulvey CM, Christoforou A, Groen A, Trotter MW, Kohlbacher O, Lilley KS, Gatto L. PLoS Comput Biol. 2016 May 13;12(5):e1004920. doi: 10.1371/journal.pcbi.1004920.
3. A subcellular map of the human proteome. Thul PJ, ........., Lilley KS, Uhlén M, Lundberg E. Science. 2017 May 26;356(6340). pii: eaal3321. doi: 10.1126/science.aal3321. Epub 2017 May 11.

How good is research at University of Cambridge in Biological Sciences?

FTE Category A staff submitted: 189.63

Research output data provided by the Research Excellence Framework (REF)

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