Understanding the function of microtubule-associated signalling networks in health and disease: role of adaptor proteins in network assembly

How do cell manage to divide, move and form tissues? And why these finely tuned processes work so well in health, but are disrupted in disease and ageing? These fundamental biological questions are highly relevant to our well-being. Despite active research, the answers are still very incomplete. In this project you will investigate the molecular system that is key to the regulation of all cell processes – microtubule (MT) signalling networks. These networks are assembled at the actively growing plus-ends of MTs. They guide MTs precisely to different area in cells, and then selectively trigger specific responses “on arrival”. Mutations of these proteins in cancer contributes to disease progression and metastasis, demonstrating their critical role. We will focus on the adaptor proteins of the MT signalling networks that control the network assembly and recruitment of other proteins through a set of inter-connected interactions.

The complexity of signalling requires the use of advanced methods from different fields of biological research. The project will start from the analysis of the molecular details of the interactions. Using NMR and X-ray crystallography you will investigate the structures of adaptor proteins complexes. This knowledge will be used to develop a set of molecular tools – mutations and cell-permeable peptides that disrupt specific interactions. You will reconstruct the networks in vitro, monitor their assembly by high-resolution fluorescent microscopy and develop a computational model of the network assembly. You will engineer a set of artificial cell substrates that reproduce conditions of healthy and pathological tumour and ageing tissues, and use them to test how MT signalling networks allow cell adoption to the environment changes with high-resolution imaging. Joining all the information together you will identify critical components of the signalling networks and test their potential as drug targets.

You will receive comprehensive training in structural biology methods, cell imaging and tissue engineering and will use state of the art research facilities of Liverpool and Newcastle. Through rotations you will work in the laboratories of each project supervisor and will interact with researches from a wide range of field. On completion you will gain a combination of multi-disciplinary expertise that is highly sought-after in academia or industry.

Informal enquiries may be made to igb2@liverpool.ac.uk

HOW TO APPLY 

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to bbsrcdtp@liverpool.ac.uk, noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.