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(BBSRC DTP) How are transport vesicles recognized in the secretory pathway?


Project Description

The secretory pathway is fundamentally important, responsible for the production of numerous proteins including growth factors, hormones, neurotransmitters, and the proteins that make up our skin and bones. Secretory pathway dysfunction is responsible for numerous diseases, including those associated with ageing, such as neurodegeneration and cancer. Consequently, it is extremely important that we understand how the secretory pathway functions at the molecular level. The Golgi apparatus lies at the heart of this pathway, where it is a hub for protein trafficking. Transport vesicles, which mediate protein trafficking, must be specifically recognized at their target compartment to ensure cargo proteins are correctly delivered within the pathway. Major players in this process are the golgin proteins, which selectively capture vesicles at the Golgi apparatus to provide the specificity necessary for transport. However, the mechanisms by which golgins capture vesicles remain to be determined.

This project aims to address this major gap in our knowledge by identifying the vesicle-associated determinants that are specifically recognised by the golgins. To achieve this, a combination of biochemical, bioanalytical and molecular cell biological methods will be employed. Protein and lipid biochemistry combined with advanced bioanalytic approaches will be used to identify candidate players, whose functions will be investigated using established microscopy, mass spectrometry and biochemistry-based functional assays. Protein function will be manipulated using CRISPR-Cas9 mediated gene editing, and dynamics of trafficking assessed using live cell imaging and super-resolution microscopy. The results will provide major new insights into the mechanisms of vesicle trafficking within the secretory pathway, a fundamentally important process.

https://www.research.manchester.ac.uk/portal/martin.p.lowe.html
https://www.research.manchester.ac.uk/portal/lynda.k.harris.html
https://www.research.manchester.ac.uk/portal/en/researchers/anna-nicolaou(a52f889c-fa1c-4efa-afc0-7f75d888a851).html

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References


Bonifacino, J.S. (2014). Vesicular transport earns a Nobel. Trends Cell Biol 24, 3-5.
Gillingham, A.K., Munro, S. (2016). Finding the Golgi: Golgin Coiled-Coil Proteins Show the Way. Trends Cell Biol 26, 399-408.
Witkos, T.M., Lowe, M. (2015). The Golgin Family of Coiled-Coil Tethering Proteins. Front Cell Dev Biol 3, 86.
Witkos, T.M., Lowe, M. (2017). Recognition and tethering of transport vesicles at the Golgi apparatus. Curr Opin Cell Biol 47, 16-23.

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