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Lipid nanoparticles (LNPs) are crucial for delivering nucleic acids into cells, powering mRNA vaccines and gene editing. While generally considered low-toxic (>24h), we observed significant intracellular nanostructure remodeling and diffusion hindrance within 4 hours of LNP exposure. Using Fluorescence Correlation Spectroscopy (FCS), we found these disturbances far exceed those from other stressors. We hypothesize that LNP lipids interact with cell membranes, causing this remodeling, potentially impacting organelle health and cellular stress. This project will use a soft matter approach and high-throughput biochemical assays, to analyze LNP-cell interactions and their biological consequences. We aim to understand the physicochemical impact of LNPs on cell membranes (1-100nm scale) and connect these findings to standard toxicity measures. This research will reveal potential adverse LNP effects, crucial for both molecular biology and clinical applications.

The responsibilities of the post-doctoral researcher will include:

• Experimental Design and Execution: designing and conducting experiments both in vitro (test tube) and in cell cultures, working with various laboratory techniques (confocal microscopy, fluorescence spectroscopy, biochemical assays, flow cytometry) and equipment.

• Data Analysis.

• Literature Review and Critical Analysis: staying up-todate with the latest research in the field, comparing new findings with previous work, and contributing to the intellectual development of the project.

• Manuscript Preparation.

We offer a post-doctoral position (full-time employment) in the Institute of Physical Chemistry PAS with a gross salary of Around 9 650 PLN gross per month financed from the NCN OPUS 27 Project no 2024/53/B/ST4/01213 Entitled “Effect of lipid nanoparticles on the nanostructure of cell cytoplasm” 100% of the work time of Postdoc will be devoted to the realization of the proposed project. The offer is for 24 months with a possible extension.

The selected candidate will gain valuable new knowledge and techniques to enhance their skill set. This project encompasses biophysics, nanotechnology, cell biology, and physical chemistry, offering a learning opportunity for individuals from diverse backgrounds. We intend to publish the findings in prestigious high-impact journals. 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. Institute provides an opportunity to participate in ERASMUS+ programme.

1. PhD degree in chemical, physical or biological sciences, obtained in the year of employment in the project or within 7 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. Extension might apply according to National Science Centre, Poland, rules.

2. Additionally, the candidate for the postdoctoral position must meet the following condition:

• they did not have the principal investigator as their research supervisor or auxiliary supervisor of their PhD dissertation;

• their PhD degree has been awarded by another institution than the one planned to employ them at this post or they have completed a continuous and evidenced post-doctoral fellowship of at least 10 months in another institution than the host institution for the project and in another country than the one in which they have been conferred a PhD degree

3. Publication record and experience in research.

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

5. Experience in at least two from the following techniques: cell culture, confocal microscopy, spectroscopy (FCS, FRET, FLIM) and/or flow cytometry.

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

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

The Recruitment Commission will take into account the following criteria: - competencies for specific tasks in the research project - knowledge in biophysics - previous scientific achievements -awards and distinctions resulting from the conducted research