PhD Studentship: Investigating novel PBF interactions in signal transduction

Signal transduction pathways coordinate various cellular responses to stimuli via altered protein expression, post-translational modifications and subcellular localisation. Pituitary tumor-transforming gene-binding factor (PBF) is a ubiquitously expressed transmembrane glycoprotein with an emerging critical role in signal transduction. PBF overexpression in vitro can induce cellular proliferation, migration, invasion, and genetic instability. Although PBF’s primary function remains unclear, our recent data reveal a physiological role in cell adhesion and motility.

Tyrosine phosphorylation is a key mediator of signalling molecule interactions. Signalling proteins with SH2 (Src Homology 2) domains modify their function and activity through binding phosphotyrosine residues and we recently identified proteins that interact with a highly phosphorylated tyrosine residue in PBF. These are well-characterised proteins in critical signalling pathways and this project will address the hypothesis that PBF is an important signalling node within these pathways.

This study will investigate protein interactions using NanoBiT, co-immunoprecipitation and GFP-TRAP assays and utilising mutant plasmids created via cloning and mutagenesis. Downstream effects of altered PBF expression levels will be investigated using siRNA knockdown, plasmid transfection, kinase activity/signalling pathway inhibitors, Western blotting and immunofluorescence analysis, and utilising CRISPR-Cas9 knockout cells and PBF-knockout mouse embryonic fibroblasts. Cellular effects of PBF interaction with these signalling molecules and pathways will be investigated by manipulating their expression and activity and measuring various functional endpoints including cell adhesion, motility, proliferation, cell cycle and DNA damage.

Overall, this project will elucidate novel interactions within critical signalling pathways and increase our understanding of signal transduction regulation of fundamental cellular processes.

Funding notes:
This is a PhD studentship with the Midlands Integrated Biosciences Training Partnership, funded by BBSRC and in partnership with the University of Warwick, Aston University, Harper Adams University, Coventry University, and the University of Leicester.

For more details please visit: https://warwick.ac.uk/fac/cross_fac/mibtp/ or https://www.birmingham.ac.uk/about/college-of-life-and-environmental-sciences/midlands-integrative-biosciences-training-partnership

How to apply:

To apply, please follow this link, make an account, and submit an application via the university online admissions portal. This link is unique to the MIBTP programme; please do not use any other link to apply to this project or your application may be rejected: https://sits.bham.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=FR167D&code2=0005

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