Industrial PhD student - Expand the druggable space of small molecules
Location: Gothenburg, Sweden
Type of employment: Temporary contract (3 years)
Pay: According to local agreement
Working hours: 100%
Start date:April/beginning of May 2025
We are looking for a highly motivated Ph.D. student to discover new inhibitors of protein-RNA interactions, in collaboration with AstraZeneca, Medicinal Chemistry department within Early Respiratory & Immunology (eR&I)and Prof. Felix Hausch from the Technical University Darmstadt.
The successful candidate will be placed within the Department of Medicinal Chemistry in early Respiratory & Immunology (eR&I), at AstraZeneca in Gothenburg, Sweden. R&I is one of AstraZeneca´s main therapy areas. With five decades of experience, eR&I is an established leader in respiratory care and a disrupter in immunology with the goal to turn ideas into life-changing medicines that improve patients´ lives and benefit society. eR&I´s chemistry team is focused on driving discovery research to deliver world-class medicines with an emphasis on molecules accessible by chemical synthesis.
The candidate will participate in a structured Ph.D. program established as part of the EU consortium Macrocycles for Drug Discovery (MC4DD) with the Ph.D. being awarded by department of Chemistry at Technical University Darmstadt.
About the project
The number of disease-causing proteins, which can be modulated by synthetic organic molecules (so-called small molecules) is limited and innovative strategies to access novel disease-causing targets are required. One approach to increase the number of targets is to modulate disease not by binding to the protein, but to the corresponding RNA to obtain the desired biological effect. This research area has gotten particular traction within the last couple of years with the one small molecule RNA binder approved by the FDA in 2020 and several more small molecule RNA binder entering the clinical phases. One of the main challenges in this field is to elucidate at which part of the target RNA sequence the small molecule has to bind to obtain the desired functional effect. If the binding site of an RNA-binding protein is known finding a small molecule which disrupts the protein-RNA-interaction can be a promising strategy to discover functional RNA binder.
In this project the successful candidate will explore novel inhibitors of disease-associated RNA-protein interactions and will work in an international multidisciplinary training network involving 8 academic and 5 industrial partners, including courses, workshops and secondments at top-ranking European universities and partners in the pharmaceutical industry.This project is part of the MC4DD European doctoral network being financed by the Marie Skłodowska-Curie Actions (MSCA) of the EU.
What you'll do?
As a PhD student within the MC4DD consortium you will be based for the majority of your Ph.D. time at AstraZeneca´s vibrant research site in Gothenburg (Sweden). Your focus will be to set-up and run assays to find novel inhibitors of disease-associated protein-RNA interactions and to synthesize analogs to improve the potency of the newly discovered inhibitors. In collaboration within colleagues at AstraZeneca and academic partners within the MC4DD consortium you will characterize the inhibitor-RNA interactions using NMR and/or X-ray crystallography.
Your Ph.D. time will also include research stays at partner institutions to facilitate your research. Additional to your scientific growth through working on your project you will also obtain an excellent education in contemporary medicinal chemistry and increase your soft skills through courses and workshops within the MC4DD consortium. Moreover, you will have the opportunity to expand your professional network both in academia and the pharmaceutical industry by interacting with consortium partners.
Main Duties and Responsibilities:
Set up assays to identify and validate inhibitors of disease-associated protein-RNA-interactions
Synthesize analogs of identified inhibitors to increase binding affinity and explore structure-activity-relationships
Investigate inhibitor-RNA interaction using NMR and/or X-ray crystallography in collaboration with colleagues at AstraZeneca and within the MC4DD consortium
Analyze data and present results at regular meetings (within AstraZeneca and the MC4DD consortium) and at renowned external conferences
Publish results in peer-reviewed high impact journals
Essential requirements
Master degree in chemistry with a focus on synthetic organic chemistry, medicinal chemistry, or chemical biology
Very good English skills in speech and writing
Excellent team-working ability to work effectively in a multi-disciplinary research environment and strong motivation to explore new frontiers in chemistry
Strong planning, organizational and time management skills
Since the position is funded by the Marie Skłodowska Curie Action (MSCA) from EU, there are specific eligibility requirements concerning mobility. Applicants must not have studied or worked in Sweden for more than 12 months during the past 36 months. Please see MSCA’s rules for doctoral networks for details
Desirable requirements
Preliminary knowledge in setting up and/or running biological assays (biophysical or cell-based) is a plus
Preliminary experience in working with RNA and/or proteins is a plus
About AstraZeneca
AstraZeneca is a global, science-driven biopharmaceutical company. We are dedicated to turn ideas into life changing medicines and strive to continuously meet the unmet needs of patients worldwide.
Our Gothenburg site is one of AstraZeneca's strategic R&D sites. Here, you'll feel a global atmosphere in a multinational environment. Collaboration comes in all forms - across teams, functions, countries and even companies. With more than 3 000 employees from over 70 countries, our vibrant Gothenburg site is a truly inspiring place to work. Here, the history and future of scientific breakthrough come together. We believe that the diversity of our people is crucial to bringing new discoveries to life.
What's next?
If you are interested, apply now! We welcome your application (CV and cover letter) no later than January 17, 2025. If you need additional information, please contact Werngard Czechtizky (at Werngard.Czechtizky@astrazeneca.com) or Stefan Schiesser (at Stefan.Schiesser@astrazeneca.com).
Where can I find out more?
AstraZeneca - Respiratory & Immunology
EU consortium MC4DD
Department of Chemistry at Technical University Darmstadt
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