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The role of vimentin in cell adhesion and motility in disease


   Department of Oncology and Metabolism

  Dr A Gad  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

This role supports an active research program to assess the molecular mechanisms underlying adhesive, mechanical and motile changes in cells as they relate to vimentin, the intracellular protein, and its assembled filamentous form in vimentin intermediate filaments. 

 Vimentin filaments has been shown in the literature to have a wide array of associations with disease, from autoimmune, fibrosis, and cancer to neurological disease. This work already establishes an essential role enabling motility, invasiveness, and amplifications of disease process, and also that vimentin filament superstructures in cells control of some of the most critical abilities to respond to disease including the activation of regulatory T cells, and the efficiency of pathogen clearance by macrophages. Vimentin presents an exciting and novel target to intervene in the mechano-biology of disease and this program has the opportunity to make a significant contribution to a field.  

This research project will assess primary vimentin properties in situ, and changes from a proprietary compound that targets vimentin. The compound alters the physical properties of vimentin filaments and our analysis aims to understand and further characterize these mechanical alterations. The project will use several in vitro and other models and assays to inform us about cell adhesion, deformation, mechanics and motility. Key tools for the study include advanced microscopy techniques, including Super-resolution microscopy, Live cell imaging and Atomic force microscopy. 

Understanding context in the literature is important for this role, given vimentin was discovered 30 years ago and accumulated an unusual body of papers showing many functions yet no essential role in normal conditions. Many other papers enumerate correlations and causalities across many disparate diseases, underscoring its potential importance as a therapeutic target. Despite this interesting profile, Vimentin has been greatly overlooked. The Gad laboratory is in a position to lead the field of vimentin cell biology into a next generation of understanding. Willingness to master this literature on vimentin, and how these contrasting biologies can co-exist is an exciting aspect of this project and its publishing opportunities.

The project will have access to proprietary compounds that target vimentin developed by a private company that is collaborating with Dr. Gad. You will work within an interdisciplinary research group on site at the University of Sheffield, UK in a diverse learning environment that presents an outstanding opportunity to develop technical skills, specific knowledge and professional scientific communication. The project provides not only the chance for exposure to novel academic, scientific, and applied learning, but a rare opportunity to experience cutting edge therapeutic development that crosses an unusual intersection of structural biology, translational implications, biomechanical measurement techniques, and cell models. Publication opportunities are expected.

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