Internal structure of lipid nanoparticles loaded with small interfering RNAs: heterogeneity and[...]

Organisation / Company Université de Strasbourg Laboratory UMR 7021 - LBP Is the Hosting related to staff position within a Research Infrastructure? No

Keywords

lipid nanoparticles, siRNA, fluorescent nucleoside analogue, Fluorescence Lifetime Imaging Microscopy, Fluorescence Correlation Spectroscopy, time-resolved fluorescence spectroscopy

Offer description

Small interfering RNA (siRNA) therapeutics are a powerful strategy for treating diseases by selectively silencing the expression of pathogenic genes through RNA interference. Their clinical translation has been enabled by lipid nanoparticles (LNPs), which protect siRNAs from enzymatic degradation, improve their pharmacokinetic profile, and facilitate cellular uptake and endosomal escape. By efficiently delivering siRNAs to target tissues, LNP-based formulations have demonstrated robust and durable gene silencing, leading to several approved therapies. Ongoing advances in LNP composition and design continue to expand the therapeutic scope of siRNA, positioning LNPs as a versatile modality for precision medicine. Despite their clinical success, siRNA-loaded lipid nanoparticles still face several key bottlenecks that limit broader application. In particular, incomplete understanding of LNP structural heterogeneity and intracellular disassembly hampers rational optimization.

In this context, the objective of the recruited post-doc is to investigate LNP structure and heterogeneity, by focusing on the structural organization of siRNAs within LNPs and its evolution during the intracellular trafficking of LNPs. This will be achieved by using a unique combination of a perfect fluorescent analogue of guanosine and advanced quantitative fluorescence spectroscopy and microscopy techniques. By labelling site-selectively siRNAs with the fluorescent analogue of guanosine, our advanced fluorescence techniques will enable to characterize the organization of siRNAs in LNPs at the single particle level both in solution and cells. Altogether the obtained data should be critical for the rational design of siRNA-loaded LNPs.

The successful candidate will ideally hold a PhD in biophysics, physics, or chemistry. Experience with fluorescence spectroscopy and/or microscopy techniques would be an asset. The postdoctoral researcher will work within a high-level, international, and multidisciplinary team at the interface of biology, chemistry, and physics. They will have access to the PIQ-QUEST microscopy platform, which includes several advanced microscopy modalities developed within the laboratory.

Who can apply?

Researchers of any nationality who:

• Have completed a PhD or will complete it at the date of the call deadline (September 2026).
• Have a maximum of 8 years full-time equivalent experience in research at the time of the call deadline.
• Have not resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 3 years immediately prior to the call deadline.

Beware that applicants who have applied to the MSCA Postdoctoral Fellowship 2025 call and received an evaluation below 80% are not eligible for an application in 2026.

How to apply?

We encourage all motivated and eligible postdoctoral researchers to send their expressions of interest to the supervisor’s e-mail address before 24th April 2026.

Your application shall include:

• a CV (5 pages max),
• a cover letter outlining your research background and its synergies with the supervisor’s field and/or the proposed research topic.

Estimated timetable

• Deadline for sending an expression of interest: 24th April 2026
• Selection of the applicant: May 2026 at the latest