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Adhesion force regulation as a mechanism of cell adaptation to tissue stiffness and composition in health and disease

  • Full or part time
    Dr I Barsukov
  • Application Deadline
    Friday, January 11, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Cells have amazing ability to adapt to different conditions. They form complex multi-cellular tissues, differentiate and migrate. Throughout the life, tissues are constantly formed, maintained and repaired. Disease, injury and old age eventually overcome regeneration processes, reducing the life span and quality. Critical part of the cell adaptation is mechanical force generated inside the cells and transmitted through the adhesion structures that connect cells to tissues. This force allows cells to probe the environment, establish contacts with tissues and other cells, move and change structure. Understanding how force is regulated will give insights on how repair system works, and will lead to new ideas on how to enhance repair processes to prolong healthy life.

This multi-disciplinary, multi-laboratory PhD project offers a unique opportunity to investigate adhesion force regulation on a molecular level in vitro with advanced methods of biochemistry and structural biology. This knowledge will guide fluorescent imaging experiments in live cells on measuring cellular forces in response to the assembly of multi-protein cellular structures. An integral part of the project is tissue engineering for developing new tissues as models for the analysis of cell interactions with the environment and, eventually as rationally designed bio-materials for wound healing and tissue regeneration. In experiments leading to this project we identified critical components of the force regulation system and defined some of their properties.

The prospective student will advance the understanding of force regulation by investigating structures of proteins complexes using X-ray crystallography and ultra-high field Nuclear Magnetic Resonance Spectroscopy. Experiments in live cells will involve high-resolution Fluorescent Imaging and traction force microscopy, supported by tissue engineering to provide tissue like environments for these cells.

The prospective student will work on rotation basis in laboratories of the three supervisors of the project, receiving full training in the fields of structural biology, cell biology and tissue engineering. The candidate will benefit from working alongside expert researches from different fields in Liverpool and Newcastle, and will have possibility to visit collaborating laboratories abroad. Beside science, she/he will experience life in Liverpool and Newcastle Universities and cities. The student will participate in outreach activities and learn how to communicate science to the lay public and to develop alternative skills (e.g. entrepreneurship, management, media, ethics) through courses and seminars regularly held at the Universities. All this will provide her/him with a wide range of skills applicable to academia, industry or other sectors.

For further information see the website: https://www.liverpool.ac.uk/integrative-biology/

To apply

Please complete the online application form and attach a full CV and covering letter. Informal enquiries may be made to

Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,777 for 2018-19). The PhD will start in October 2019. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.

References

Lilja, J., Zacharchenko, T., Georgiadou, M., Jacquemet, G., De Franceschi, N., Peuhu, E., Pouwels, J., Beifuss, M., Boeckers, T., Kreienkamp, H.-J., Barsukov, I. (joint corresponding author) and Ivaska, J. (2016). SHANK3 structure reveals a Ras-associated domain regulating integrin activation, Nature Cell Biol, 19, 292.

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