DC15: Establishing a toolbox of warheads for covalent targeting of RNA

PhD project description:

The PhD project will focus on the design, synthesis, and characterization of covalent warheads targeting the 2’OH group in RNA nucleotides to create a broad toolbox to enable the discovery of covalent RNA ligands. Binding parameters will be optimized for both reversible and irreversible covalent binders, including time bound within the RNA, by tuning both steric and electronic properties of the warheads. Synthetic modification of warheads and synthesis of analogues will be essential to drive the discovery forward. The flavin mononucleotide (FMN) riboswitch will be used as model system for validating the warheads. Promising warheads will be appended onto the scaffold of known FMN riboswitch ligands to obtain covalently binding FMN ligands.

You will be responsible for the screening of commercially available candidate warheads and characterization of stability and identity of their adducts. Utilizing identified warheads, you will take part in the design of novel target compounds for synthesis and will be responsible for the development of synthesis routes, and synthesis of the target compounds. You will be tasked with developing new synthesis routes and using these to produce compound libraries for the purpose of establishing structure-activity relationships.

You will work in a team together with other synthesis- and medicinal chemists both within the TargetRNA doctoral network and the research group. The work tasks will be varied, and you will be given the opportunity to contribute to developing new solution in a research environment that focuses on innovation. Testing in biochemical assays will be carried out by other project members as well as external partners.

You are expected to co-supervise MSc-students and participate actively in professional activities within the TargetRNA network, the research group and at the Department of Chemistry.

Research environment:

The PhD position is associated to the Haug research group, which is part of the research group for Bioresources and Pharmaceutical Chemistry.

Skills/qualifications:

• Applicants must hold a master's degree or equivalent education in organic synthesis or medicinal chemistry. Master students can apply provided they complete their final master exam before 01.11.2024. It is a condition of employment that the master's degree has been awarded.
• Applicants must have a documented solid background within synthesis of small organic molecules.
• Experience from structural characterization of organic molecules using NMR spectroscopy is a requirement.
• Experience with other analytical techniques such as HPLC, MS and LC-MS is an advantage.
• Experience from medicinal chemistry projects is an advantage.
• Experience in molecular modelling / docking is an advantage.
• Applicants must be able to work independently and in a structured manner and demonstrate good collaborative skills.
• Applicants must be proficient in both written and oral English.

Personal and relational qualities will be emphasized. Ambitions and potential will also count when evaluating the candidates. 

Special requirements for the position: The University of Bergen is subjected to the regulation for export control system. The regulation will be applied in the processing of the applications. 

About the research training: As a PhD Research Fellow, you must participate in an approved educational programme for a PhD degree within a period of 3 years. The deadline for applying for admission to the PhD programme at The Faculty of Mathematics and Natural Sciences is 2 months after you start your position or after the start of the research project that will lead to the PhD degree. It is a condition that you satisfy the enrolment requirements for the PhD programme at the University of Bergen. Please include approved documentation of proficiency in English (if required, cf. English language requirements for PhD admission).

Benefits/salary/social security:

• Exciting development opportunities as part of your role in a strong professional environment.
• Salary as PhD research fellow (code 1017) in the state salary scale. This constitutes a gross annual salary of NOK 540 500 (equivalent to pay grade 55). Further increases in salary are made according to length of service in the position. 
• Enrolment in the Norwegian Public Service Pension Fund.
• Good welfare benefits.

State employment shall reflect the diversity of Norwegian society to the greatest extent possible. People with immigrant backgrounds and people with disabilities are encouraged to apply for the position.The University of Bergen applies the principle of public access to information when recruiting staff for academic positions. Information about applicants may be made public even if the applicant has asked not to be named on the list of persons who have applied. The applicant must be notified if the request is not met. Further information about our employment process can be found here.

For more information about the position, please contact Bengt Erik Haug.