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ICL

Rewiring Cancer Targets Through Proteome-Wide Discovery of Molecular Glues

Imperial College London Department of Chemistry
✓ Fully Funded ⏰ Closing Soon 🎓 Biochemistry 🎓 Molecular Biology 🎓 Pharmaceutical Chemistry machine learning translational research drug discovery proteomics molecular glues chemical biology protein-protein interactions cancer targets

Explore how molecular glues can rewire protein interactions to target cancer. Develop proteomic and data-driven methods to discover new drug modalities across the entire proteome.

AI-generated overview

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Why This Research Matters

This research could transform cancer treatment by enabling drugs to target previously inaccessible proteins through induced proximity mechanisms. It opens new therapeutic strategies that go beyond traditional inhibition, potentially improving specificity and reducing side effects.

Chemical Biology

Project Description

Project Overview

Molecular glues are small molecules that rewire cellular interaction networks by stabilizing or inducing protein-protein interactions, allowing selective targeting of proteins previously considered undruggable. This project aims to establish a new discovery platform, PRISM, to map such interactions throughout the proteome and uncover new therapeutic modalities.

What You Will Do

The student will develop high-throughput proteomic workflows to identify ternary complexes and validate molecular glue activity using biophysical and cellular assays. They will link the induced interactions to functional outcomes in disease-relevant models, applying machine learning to predict and design novel molecular glues.

Expected Outcomes

The research will generate a unique dataset of glueable protein-protein interactions and develop methods to predict molecular glues, providing new avenues for translational drug discovery and potential cancer therapies.

Why This Matters

By enabling selective modulation of challenging biological targets, molecular glues could revolutionize drug discovery and cancer treatment, offering mechanisms beyond conventional inhibitors like degradation, sequestration, and transcriptional control.

Entry Requirements

Candidates should have a strong background in chemistry or chemical biology and an interest in quantitative and data-driven approaches to biological systems.

Eligibility

UK/Home
EU
International

Supervisor Profile

PE
Professor Ed Tate
Imperial College London, Department of Chemistry
14299 Citations
62 h-index
Google Scholar

Professor Ed Tate is a leading figure in chemical biology at Imperial College London. His research focuses on developing chemical tools to probe biological systems, emphasizing innovative approaches to drug discovery. He has extensive expertise in proteomics, molecular glues, and targeted protein degradation, contributing significantly to understanding complex protein networks in disease.

Key Publications

2019 3305 citations
FSP1 is a glutathione-independent ferroptosis suppressor
2020 337 citations
Antibody–PROTAC conjugates enable HER2-dependent targeted protein degradation of BRD4
2010 336 citations
Protein myristoylation in health and disease
2014 283 citations
Global profiling of co- and post-translationally N-myristoylated proteomes in human cells
2011 260 citations
Activity-based probes: discovering new biology and new drug targets

Research Contributions

Investigated protein lipidation such as myristoylation and its role in health and disease.
Provided novel insights into protein modifications that influence cellular function and drug target discovery.
Developed antibody-PROTAC conjugates for targeted protein degradation.
Advanced therapeutic approaches enabling selective degradation of disease-relevant proteins.
Profiled co- and post-translational modifications using chemical proteomic technologies.
Enhanced understanding of protein function and regulation at the proteome-wide level.

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