Thesis work: CRISPR screen to identify Antisense Oligonucleotides

Job description
Genome-wide CRISPR screen to identify the Antisense Oligonucleotides (ASO)-interacting proteins involved in ASO efficacy


Would you like to apply your cell biology expertise to improve the efficacy of innovative medicines in a company that follows the science and turns ideas into life changing medicines? Then AstraZeneca might be of interest to you!
 
Thesis type: 60 credits


Project start: January 2024


Student location: On Site, Gothenburg Sweden



Antisense oligonucleotides (ASO) therapy can be created for any patient, any target, including targets that have long been considered “un-druggable” by traditional therapies. More than 12,000 patients have been safety treated with ASO medicines across many disease areas. Even though these molecules are currently prescribed, their mechanisms of entry and action remain poorly understood. Moreover, the majority of diseases targeted by ASO requires recurrent ASO injections. Thus, ASO efficiency should be improved to reduce the amounts of delivered-ASO and their consecutive toxicities. Our ultimate goal is to better know the ASO route(s) and proteins involved in these routes to design ASO favouring one route to improve ASO efficiency. Previous studies are mainly based on mass spectrometry analysis to identify ASO-interacting proteins. Here, we plan to perform a functional characterization of all coding genes to identify the proteins improving or limiting the ASO efficiency. The originality of the project is based on three key elements: our skills to perform genome wide CRISPR based screens (Gautron A., Embo Mol Med 2021), our collaboration with SciLifeLab (Stockholm) and our capability to perform biochemical validations of ASO-protein interactions (assays already developed in our team). Beyond the elucidation of the molecular mechanism of ASO internalization and cell trafficking, identifying key ASO-protein partners can impact future ASO-biomedical applications.
 


At AstraZeneca, all of our employees make a difference to patients’ lives every day. We operate in more than 100 countries around the world and are one of Sweden’s most important export companies.
 
With more than 2,400 employees from 50 countries, the vibrant Gothenburg site helps to support the entire life-cycle of AstraZeneca medicines, from drug discovery and clinical trials, to global commercialisation and product maintenance. Gothenburg is one of AstraZeneca’s three strategic, global R&D centres, alongside Cambridge and Gaithersburg, and plays a central role in our mission to deliver life-changing medicines to patients.
 


Application
Randstad Life Sciences is collaborating with AstraZeneca in this recruitment process. Please send your application in English and we only accept applications through Randstad’s website.



Deadline for application: 2023-10-16, selection and interviews will be ongoing. The position may be filled before the last day of application, therefore, apply as soon as possible.




Responsibilities
Our goal is to 1) Identify the proteins involved in ASO uptake and ASO guidance to their RNA-targets using a genome wide approach (CRISPR screen), 2) Confirm the ASO-protein partners by biochemical approaches and imaging. You will mainly involve in the first part of the project by assuming the cell culture part of the CRSIPR screen with your supervisor.

Qualifications
Essential Requirements 
Cell biology or Genetic background
Cell culture experience
Knowledges on CRISPR approaches



Desirable Requirements 
Knowledges on Oligonucleotides


About the company
If you’re inspired by the possibilities of science to make a difference and ready to discover what you can do – join us! 


At AstraZeneca we are guided in our work by a strong set of values, and we’re resetting expectations of what a bio-pharmaceutical company can be. By truly following the science, we pioneer new methods, new thinking and bring unexpected teams together. From scientists to sales, lab techs to legal, we’re on a mission to turn ideas into life-changing medicines that transform lives. We need great people who share our passion for science and have the drive and determination to meet the unmet needs of patients around the world. If you’re swift to action, confident to lead, willing to collaborate, and curious about what science can do, then you’re our kind of person.


AstraZeneca is an equal opportunity employer. AstraZeneca will consider all qualified applicants for employment without discrimination on grounds of disability, sex or sexual orientation, pregnancy or maternity leave status, race or national or ethnic origin, age, religion or belief, gender identity or re-assignment, marital or civil partnership status, protected veteran status (if applicable) or any other characteristic protected by law. AstraZeneca only employs individuals with the right to work in the country/ies where the role is advertised.