Thesis work, 60 credits - Reverse Transcriptase Engineering and Optimization for Genome Editing

Are you ready to be at the forefront of revolutionary science? Join the Genome Editing Technologies (GET) team at AstraZeneca and contribute to cutting-edge research aimed at curing genetic diseases. In our vibrant, international collective, you'll work with world-class scientists on groundbreaking genome editing tools. Together, we’re pushing the boundaries of molecular biology to change the future of medicine. 

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 description:

The Genome Editing Technologies (GET) team at AstraZeneca is tasked with developing and applying cutting-edge molecular tools for the primary purpose of curing genetic diseases. We are a vibrant, international collective of scientists with a wide range of expertise that creates an environment where impactful science thrives. Seize this opportunity to join the GET team, where you will undertake the project of developing reverse transcriptases for genome editing. 

Reverse transcriptases (RTs) are enzymes that, when discovered in 1970, disrupted the central dogma of molecular biology. Nowadays, these RNA-templated DNA polymerases have found their way into the genome engineering field as a crucial part of Prime Editing (PE) strategy. In prime editing, RTs are coupled with targeted nucleases and a suitably designed RNA to implement precise edits into the genome. However, the efficiency of PE is often an issue, and efforts to improve this technology are highly desirable. 

The aim of this project is to enhance the performance of reverse transcription in prime editing. The candidate is expected to execute at least one, and preferably more, Design-Make-Test-Analyze (DMTA) cycles on the Prime Editing RT component. Within this framework, the candidate will be exposed to and have the chance to learn a variety of in silico and experimental approaches. 

• Design: Leverage structural prediction (AlphaFold, ESM fold), structural analysis (PyMol, UCSF Chimera), literature review, and biochemical RT diagnostic data to introduce potential gain-of-function mutations into an RT. 
• Make: Construct plasmids for the expression of modified constructs in mammalian cells. 
• Test: Benchmark your designs using our cutting-edge mammalian reporter cell lines. Run NGS validations as needed. Generate biochemistry/biophysics data to inform future DMTA cycles. 
• Analyze: Process and organize data in a concise manner to report new findings and inform the next DMTA cycle. Writing a master's thesis based on performed experiments is expected. 

Join our team and let’s make some great RTs together! 

Requirements: 

• Pursuing a Master's Degree in a relevant field of study. 
• Background in: Cell biology, genetics, molecular biology, structural biology, biochemistry, chemistry, or related fields is a plus. 
• Have a strong drive for learning and scientific curiosity. 
• Be passionate about developing molecular tools with potential to impact genetic diseases. 
• Be excited about the opportunity to work with cutting-edge genome editing technologies. 
• Possess strong problem-solving skills and the ability to work independently and as part of a team. 
• All necessary training and support will be provided, so prior experience in all areas is not required. 

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 15th of December2024. 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.  

AstraZeneca embraces diversity and equality of opportunity. We are committed to building an inclusive and diverse team representing all backgrounds, with as wide a range of perspectives as possible, and harnessing industry-leading skills. We believe that the more inclusive we are, the better our work will be. We welcome and consider applications to join our team from all qualified candidates, regardless of their characteristics. We comply with all applicable laws and regulations on non-discrimination in employment (and recruitment), as well as work authorisation and employment eligibility verification requirements.