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 firstname.lastname@example.org
HOW TO APPLY
Applications should be made by emailing email@example.com 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 firstname.lastname@example.org, 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.
Open to students worldwide
Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
1. (2017). Targeting SxIP-EB1 interaction: An integrated approach to the discovery of small molecule modulators of dynamic binding sites. Sci Rep. 7,15533.
2. (2016). SHANK3 structure reveals a Ras-associated domain regulating integrin activation, Nature Cell Biol, 19, 292.
3. (2020). Relief of talin autoinhibition triggers a force-independent association with vinculin. J Cell Biol., 219(1)
4. (2019) Assessment of corneal substrate biomechanics and its effect on epithelial stem cell maintenance and differentiation. Nat. Comms. doi: 10.1038/s41467-019-09331-6.
5. 4D Corneal Tissue Engineering: Achieving Time‐Dependent Tissue Self‐Curvature through Local-ized Control of Cell Actuators. Adv. Func. Mater. doi: 10.1002/adfm.201807334.
6. (2018) Autogenous Biofabrication of Nativelike, Scaffold-Free Human Skin Equivalents Using a Smart, Enzyme-Degradable Tissue Templating Coating. ACS Appl. Bio Mater. doi: 10.1021/acsabm.8b00685.
7. Membrane tension orchestrates rear retraction in matrix directed cell migration. Developmental Cell https://doi.org/10.1016/j.devcel.2019.09.006
8. Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis. EMBO Journal 2019 Jun 3;38(11).
9. HRS-WASH axis governs Actin mediated endosomal recycling and cell invasion. Journal of Cell Biology 2018 Jul 2;217(7):2549-256
10. STEF/TIAM2 mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nature Communications 2018 May 29;9(1):2124