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  How do post-translational modifications regulate microtubule severing enzymes?

   Department of Chemistry

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  Dr Barbara Ciani  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Microtubule severing enzymes control when and how cells divide therefore they need to be strictly regulated to avoid cutting their substrate indiscriminately. Chemical modifications of key aminoacids allow specialised function at the cellular sites of local enrichment but how this chemistry specifically controls the structural communication between functional regions of this class of molecules and how this feedback to pathways track regulating cellular protein levels, is not fully understood. But, microtubule severing enzymes belong to a larger protein family whose members operate on diverse substrates even if sharing functional domain arrangements.

This project aims to establish a general mechanism for the regulation of the activity of the AAA-ATPases family of microtubule severing enzymes. To this purpose, we will investigate the crosstalk between chemical modification, structural rearrangement and microtubule severing activity of the AAA-ATPase Spastin and test the relevance of this mechanism to other AAA-ATPases working at different cellular locations or on diverse substrates. Spastin activity is crucial in diverse cellular processes ranging from cell division to several neuronal functions and alterations of Spastin regulation have been observed in tumors and are pathogenic in various neurodegenerative diseases.

We are looking for an enthusiastic and committed student to study the regulation of the AAA+ ATPase enzyme Spastin by post-translational modifications.

You will be trained in molecular biology, biochemistry and biophysical chemistry techniques to characterise enzyme kinetics, protein structure and protein-protein interactions. Your findings will have major impact in biochemistry and cell biology but also areas like synthetic biology. The knowledge generated will translate in novel approaches to treat neurodegenerative diseases and cancer.
Biological Sciences (4)

Funding Notes

This is a self-funded project.

If you hold a 2.1 honours masters level degree in Chemistry, Biochemistry or equivalent and are interested in developing new drug-like biomolecules, please get in touch with Dr Ciani ([Email Address Removed]).

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