Thesis work, 45 credits - HyTting the (un)PROTACables: Exploring the Potential of Hydrophobic Tag-Based Protein Degradation

Are you ready to push the boundaries of drug discovery? Join us at AstraZeneca to explore a novel approach to Targeted Protein Degradation (TPD) with groundbreaking potential. This thesis project will focus on advancing a new TPD strategy using Hydrophobic tags (HyT), offering a fresh perspective on targeting “undruggable” proteins. 

About AstraZeneca: 

AstraZeneca is a global, science-led, patient-centred biopharmaceutical company focusing on discovering, developing, and commercialising prescription medicines for some of the world’s most serious diseases. But we’re more than a global leading pharmaceutical company. At AstraZeneca, we're dedicated to being a Great Place to Work and empowering employees to push the boundaries of science and fuel their entrepreneurial spirit.  

About the Opportunity: 

As a Thesis Worker at AstraZeneca, you’ll find an environment that’s full of unique opportunities and exciting challenges. Here, you’ll have the opportunity to pursue your areas of interest whilst equally developing a broad skillset and knowledge base to get the best out of your experience. You’ll be working on meaningful projects to make an impact and deliver real value for our patients and our business. 

Thesis work description:  

Targeted protein degradation (TPD) has emerged as a promising strategy for drug development, offering innovative avenues for targeting previously undruggable proteins. A key approach in this field involves PROTACs (PROteolysis TArgeting Chimeras), which are small molecules designed to selectively degrade proteins of interest, and are being extensively utilized as tools for TPD. 

This thesis project will focus on evaluating the potential of a novel TPD strategy using Hydrophobic tags (HyT). HyT-protein degraders are bifunctional molecules, akin to PROTACs, comprising a ligand for the protein of interest (POI), a middle linker, and a highly hydrophobic group. This hydrophobic group binds to the surface of target proteins with hydrophobic moieties. Typically, the hydrophobic domains of stable proteins are sequestered within the protein structure. However, when these hydrophobic domains are exposed on the protein surface, cells interpret them as unstable or misfolded proteins, leading to the degradation of these proteins via protein quality control mechanisms. 

This thesis has the potential to uncover new possibilities in the TPD space of drug discovery strategy at AstraZeneca, shedding light on the innovative use of Hydrophobic tags as a means of targeted protein degradation. 

Objectives: 

• Evaluate HyT-degraders targeting key proteins within the AstraZeneca portfolio. 
• Test these molecules in cell-based assays with both cell lines and primary cells. 
• Investigate the mechanism of action through advanced cellular techniques. 

Essential Requirements: 

• Ongoing Master's Studies in a relevant discipline, supported by a degree in Biological Sciences/Bioengineering 
• Experience working within a laboratory environment and aseptic mammalian cell culture 
• Enthusiastic for addressing novel aspects of early-stage drug discovery 

So, what’s next?  

Apply today and take the chance to be part of making a difference, making connections, and gaining the tools and experience to open doors and fulfil your potential. We can´t wait to hear from you!  

We welcome your application as soon as possible, but ahead of the scheduled closing date 10th of November 2024. In the event that we identify suitable candidates ahead of the scheduled closing date, we reserve the right to withdraw the vacancy earlier than published.