Thesis work, 60 credits - Enhancing the PAM Range and Specificity of CRISPR/Cas9 through Engineering and Evolution

Are you ready to push the boundaries of drug discovery? We are looking for a master student who wants to enhance the Cas9 enzyme through laboratory-directed protein evolution in this cutting-edge master thesis.  

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:

Background: The discovery of the bacterial CRISPR-Cas system and its subsequent development into a powerful genome-editing tool has revolutionized the field of genetic research and holds immense potential for treating genetic diseases. This system, composed of a single guide RNA (sgRNA) and the Cas9 nuclease, enables precise DNA editing by inducing double-strand breaks at targeted locations. The cell’s repair mechanisms—either error-prone or highly accurate—can then modify or disrupt the target gene. CRISPR-Cas9's customizable design and user-friendly interface have led to its widespread application in drug discovery and gene therapy. 

However, a key limitation of CRISPR-Cas9 is its dependency on a specific DNA sequence, the protospacer adjacent motif (PAM), which must be present near the target site for successful genome editing. This sequence requirement, dictated by interactions between the sgRNA and the DNA, restricts the range of targetable genomic regions. This limitation highlights the need for more versatile genome-editing tools. 

Project Overview: The goal of this project is to enhance the Cas9 enzyme through laboratory-directed protein evolution. By applying targeted mutagenesis and selective pressure, we aim to develop Cas9 variants with broader PAM compatibility, expanding the range of genomic sites that can be edited. This approach will contribute to the creation of more universal and efficient genome-editing tools. 

Requirements: 

• Pursuing a Master's Degree in a relevant field of study. 
• Strong passion for scientific research and a keen willingness to learn and develop new skills. 
• Proactive and goal-driven, with a focus on achieving results and advancing projects. 
• Proven ability to work collaboratively within teams, contributing effectively to collective success. 
• Excellent problem-solving skills, with the ability to analyze complex issues and implement practical solutions. 

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 8th of December 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.