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Precision Medicine DTP - Understanding the role of novel microtubule-associated proteins in controlling cell division, organization and shape


School of Biological Sciences

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Dr Julie Welburn , Dr J Marsh No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

Background
Cell organization is determined by the intracellular organization of its cytoskeleton. In particular Microtubules (MTs) are long dynamic polymers made of heterodimers of tubulin- and tubulin-, which underlie many essential processes ranging from cell polarity to transport and cell division. Recently, many new microtubule proteins, associated with both the inner and outer microtubules, have been discovered from structural studies. However, very little is known about their biology function. Given the growing number of sporadic tubulin mutations identified from patient genome sequencing and associated with a wide range of diseases, it is important to understand the role of these new proteins both in basic biology of the cell but also identify orphan diseases that may be associated with these uncharacterized proteins.
The exciting project will aim to define the function of these novel proteins and examine their conservation across eukaryotes at the cellular and molecular level, and determine whether they are implicated in human diseases, for which the causes are not known so far. The student will use a cell biology and biochemistry approaches to define the function of these proteins in vivo and in vitro using molecular biology, cell biology and biochemistry. Using a computational approach, the student will search genomic patient data to identify mutations in these proteins that could be associated with pathogenicity. The mutations will be modelled in silico to the available protein structures bound to microtubules and the effect of the mutations on microtubule function will be tested in vitro and in vivo. If we want to develop personalized treatments to treat diseases ranging from tubulinopathies to cancers, it is critical to determine the molecular basis for the function of microtubule-associated proteins, identify the disease-causing mutations and understand their underlying pathogenic mechanism.

Training outcomes

This project offers the student the opportunity to learn biochemical and cell biology approaches in the Welburn lab (in vitro reconstitution of complex systems, advanced light microscopy and super-resolution microscopy, image analysis, genome editing) and to learn and develop computational methodology in bioinformatics, machine learning and protein modelling in the Marsh lab. Overall, this exciting project offers the student the opportunity to gain experience in integrating both experimental and computational approaches for identifying damaging genetic variants.

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.

For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine

Funding Notes

Start: September 2021

Qualifications criteria: Applicants applying for an MRC DTP in Precision Medicine studentship must have obtained, or will soon obtain, a first or upper-second class UK honours degree or equivalent non-UK qualification, in an appropriate science/technology area. The MRC DTP in Precision Medicine grant provides tuition fees and stipend of at least £15,285 (UKRI rate 2020/21).

Full eligibility details are available: http://www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

Enquiries regarding programme: [Email Address Removed]
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