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Proteomics to determine how defects in membrane trafficking within the secretory pathway cause human disease


   Faculty of Biology, Medicine and Health


Manchester United Kingdom Biochemistry Cell Biology Medicine Pharmacology

About the Project

Work in the Lowe laboratory is aimed at deciphering the molecular mechanisms that control membrane trafficking within cells. A major focus of our work is the trafficking of proteins to and through the Golgi apparatus, which lies at the heart of the secretory pathway. Recent advances have identified many of the key players in secretory trafficking, but the mechanisms by which many of these proteins function are poorly defined. Moreover, it is known that mutation of a number of these trafficking factors causes disease in humans, but the underlying mechanisms remain to be determined. Amongst the various proteins of interest to us are members of the golgin family and proteins related to the golgins, whose loss in vivo can lead to a number of tissue-specific phenotypes that include neurodegeneration, bone malformation and osteoporosis, and skin abnormalities similar to those seen in ageing.

A project is available in the lab to better understand how the golgins and related proteins function in membrane trafficking within the secretory pathway. The project will employ a combination of methods to reveal how these proteins function in healthy cells, but also how their function is altered in disease. Amongst these methods is CRISPR-mediated genome editing, to generate modified versions of the proteins at endogenous levels, and proteomics, which allows the identification of associated protein complexes and post-translational modifications in an unbiased and systematic manner. These approaches will be combined with cell biology experiments to determine the functional roles of the golgins and related proteins in specific protein trafficking events within cells.

Training will be provided in mammalian cell culture, molecular cloning, genome editing using CRISPR, various microscopy techniques including fluorescence microscopy, and proteomics.

For further details about our work please see https://www.research.manchester.ac.uk/portal/martin.p.lowe.html, or feel free to contact Prof Martin Lowe for further details on the various available topics at

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk


Funding Notes

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in cell biology or proteomics, or with an interest in protein trafficking, are encouraged to apply.

This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

References

Gillingham and Munro (2016). Finding the Golgi:Golgin coiled-coil proteins show the way. Trends Cell Biol. 26, 399-408.

Hennies et al (2008). Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin. Nat. Gen. 40, 1410-1412.

Liu et al (2017). Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice. Proc. Natl. Acad. Sci. 114, 346-351

Witkos and Lowe (2016). The golgin family of coiled-coil tethering proteins. Front. Cell Dev. Biol. 3: 86.

Witkos and Lowe (2017). Recognition and tethering of transport vesicles at the Golgi apparatus. Curr. Op. Cell Biol. 47, 16-23.

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