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Dioxygenases use molecular oxygen to modify their substrates, which can include proteins, nucleic acids, fatty acids, and small molecules. Because of their versatility, dioxygenases are involved in many essential cellular processes, such as breaking down fatty acids, signalling, and regulating gene expression. Dioxygenases are also important drug targets, and many widely used medicines work by blocking their activity.

Understanding how dioxygenases function, what substrates they act on, how they perform their reactions at the molecular level, and what their three-dimensional structures look like is crucial for developing medicines.

The objectives of this project are to characterise the function, substrates, and structure of two unusual human dioxygenases related to cancer. This knowledge, together with artificial intelligence-based methods, will be used to guide the development of molecules that selectively block the activity of these two dioxygenases to enable future cellular studies on their potential as cancer targets.

This project will employ a combination of state-of-the-art laboratory techniques to produce these two human dioxygenases in bacterial cells, to identify the natural molecules they modify (using e.g. NMR, MS, plate reader-based activity assays), and to determine their three-dimensional structures (using e.g. protein crystallography); part of the work will be carried out together with international collaborators. Collectively, the results of these investigations will inform on how these two dioxygenases work at the molecular level and will help to define their roles in both healthy and cancer cells.

Responsibilities:

• Independently design, plan and conduct experiments related to the biochemical and structural characterisation of human dioxygenases
• Design, express and purify protein constructs
• Develop and perform enzyme activity assays
• Structurally characterise proteins
• Analyse data
• Effectively work together with students and international collaborators
• Oversee the work of students
• Disseminate research results at project meetings, in peer-reviewed journals and at international conferences

We offer a post-doctoral position (full-time employment) in the Institute of Physical Chemistry PAS with a gross salary of around 11700 PLN per month financed from the NCN OPUS 30, Project no. 2025/59/B/NZ1/02711, entitled “Functional and Structural Characterization of Predicted Human Oxygenases with an Unusual Fe(II)-Binding Site”.

100% of the work time of Postdoc will be devoted to the realization of the proposed project. The offer is for 12 months with the possibility of extension.

• The candidate will have the opportunity to work in a highly ambitious young research group at the interface of biochemistry, structural biology, and medicinal chemistry and perform work with high translational potential
• The candidate will have the opportunity to build an expertise in a plethora of state-of-the-art biochemical and biophysical techniques
• The candidate will have an opportunity to work in the laboratory of an international collaborator for some time
• The candidate will have an opportunity to present their work at international conferences
• The successful candidate will be eligible for all programs at the IPC PAS, including the IPC PAS Young Scientists competition and the IPC PAS Young Scientists Mobility competition. The IPC PAS provides the opportunity to participate in ERASMUS+ programme.

• A PhD degree in chemistry, biochemistry, or related scientific disciplines is required, obtained in the year of employment in the project or within 12 years before 1 January of the year of employment in the project. For researchers with multiple PhDs, the date of the first PhD award is deemed the reference date. Extensions might apply according to the rules of the National Science Centre, Poland;

• Additionally, the candidate for the postdoctoral position must meet the following condition: their PhD degree has been conferred by an institution other than the one employing them at this position. Otherwise, they must have completed a continuous and evidenced research fellowship of at least 9 months during their studies at the doctoral school, doctoral studies or after being conferred their PhD degree at another institution than the participating entity for the project and outside the country in which their PhD degree was conferred.

• Publication record and experience in research.

• Ability to work independently as well as in a group.

• Experience with at least one of the list: (preferably two or more):

1. Recombinant protein production

2. Protein purification

3. Enzyme activity assays and kinetics

4. Structural/crystallographic characterisation of proteins

5. Medicinal chemistry

• Ability to communicate fluently in English (written and spoken).

• Strong motivation to work and solving scientific problems, creativity, and analytical thinking.

The Recruitment Commission will take into account the following criteria:

• Competence to perform specific tasks in the research project
• Previous scientific achievements, awards and distinctions resulting from prior conducted research.