Application deadline: 08 Dec 2023
Institute: Systems Biology Ireland, University College Dublin
More information: https://www.ucd.ie/workatucd/jobs/
University College Dublin (UCD) is seeking applications for a Postdoctoral Research Fellow to work on the mapping of dynamic changes in protein complexes using modern MS-based proteomics methods.
Drug resistance is a major challenge in oncology. Increasing evidence highlights the importance of nongenetic mechanisms. Here, we investigate the role of protein-protein interactions (PPIs) in drug resistance. We study whether drug induced PPI changes can reorganize multi-protein complexes (MPCs) in signaling pathways, thereby leaving a ‘memory’ of drug exposure that facilitates successful adaptation and resistance. As result we expect to identify new targets for therapeutic interference that extend the current narrow range of molecular oncology targets. As use case we focus on neuroblastoma, a childhood cancer where new drug targets are needed to replace genotoxic chemotherapy with its severe long-term side effects. Based on our previous results that stress signaling is critical for chemotherapy response we analyze drug induced PPI changes in stress pathway MPCs using quantitative proteomics. This targeted approach is complemented by a global mapping of MPCs changes using thermal proximity coaggregation. Our preliminary evidence also suggests that RNA can function as scaffold for MPCs. Therefore, we will assess the role of such scaffolding RNA for re-modelling MPCs in drug resistance. To causally link MPC changes to drug resistance we will employ artificial dimerizer systems to control several PPIs simultaneously and test how this modulates drug resistance.
This project is teamwork combining molecular biology, proteomics, and bioinformatics. The successful applicant will perform the proteomics experiments in the team. To be successful in the role, the Fellow will have experience in MS based proteomics (interaction proteomics, phosphoproteomics and protein expression profiling) and protein biochemistry. An understanding of cancer signalling and protein-protein interaction networks is also required. The Fellow should be self-motivated and comfortable working with collaborators
from different disciplines. This post will be part of a team and perform the proteomics analysis of the project.
The team will be part of Kolch Group at Systems Biology Ireland (SBI, http://www.ucd.ie/sbi/), a research centre based on the UCD Belfield Campus. SBI was established in 2009, and has successfully developed an integrated mathematical/computational modelling and experimental research programme focusing on the design of new therapeutic approaches to cancer, based on a systems level, mechanistic understanding of cellular signal transduction networks.
To apply, go to https://www.ucd.ie/workatucd/jobs/ and search for Job ID: 016578.
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