Upconversion nanoparticles functionalized with lipid specific peptides for long-term studies of the dynamics of lipid domains in living cells

18 Jan 2024
Job Information

Organisation/Company

University of Strasbourg

Department

Faculty of Pharmacy

Research Field

Physics » Biophysics
Chemistry » Physical chemistry

Researcher Profile

Recognised Researcher (R2)

Country

France

Application Deadline

23 Feb 2024 - 12:00 (Europe/Paris)

Type of Contract

Temporary

Job Status

Full-time

Hours Per Week

35

Offer Starting Date

4 Mar 2024

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

Start date: The postdoctoral position is funded for one year and may start from March 2024.

Candidate profile: We are looking for a highly motivated candidate with a background in physico-chemistry, biophysics or physics, and a strong interest in microscopy techniques and their applications in biology.

We value creativity and autonomy. Prior experience is expected in several of the following fields: microscopy, spectroscopy, fluorescence, upconversion luminescence, formulation/ functionalization of nanoparticles. Knowledge of Matlab or another programming language would be appreciated.

Scientific background:  The plasma membrane is highly dynamic and exhibits strong lateral heterogeneity due to the formation of transient ordered lipid nano-domains (NDLs), enriched in sphingomyelin (SM) and cholesterol (Chol), which can recruit other lipids and proteins. These NDLs are thought to play a key role in numerous cell functions and pathologies. However, the mechanisms governing and regulating this heterogeneity are poorly understood due to difficulties to visualize and track these small and highly dynamic NDLs. Single Particle Tracking (SPT) is a powerful technique for studying membrane dynamics and organization. However, it is limited by the lack of probes available for the long-term monitoring of endogenous lipids and lipid domains with good spatial and temporal resolution over large fields.

Objective: This project aims to address these challenges by developing innovative SMT probes based on the novel combination of upconverting nanoparticles (UCNPs) and lipid-specific peptides (LBPs), capable of recognizing dispersed SM molecules, clusters of SM, and domains enriched in SM/Chol or Chol. This project relies on two major areas of expertise of the host laboratory. One area concerns optical characterization, coating and functionalization of UCNPs and single particle imaging.[1] Anti-Stokes emission of UCNPs enables backgroundless luminescence imaging, while their extreme photostability and non-blinking luminescence allow to record very long trajectories in SPT measurements.[2] The second area consists in the development of protein probes that specifically bind to SM and Chol, two main components of NDLs.[3] These ligands based on non-toxic domains or mutant toxins specifically target lipids, while minimally disturbing the targeted lipids.

The project includes four activities. Activity 1 focuses on the characterization of small (<20 nm) UCNPs based on NaYF4 doped with Yb3+ and Er3+ and NaYbF4 alloy doped with Er3+ having a core-shell geometry synthesized by our collaborator. Activity 2 focuses on the coating of UCNPs with phospholipids to ensure good colloidal and chemical stability of UCNPs as well as high brightness in aqueous solution while limiting their non-specific adsorption to cells. In Activity 3, modified phospholipids, displaying functional groups will be used to couple LBPs to UCNPs and to test them on model membranes. The objective of Activity 4 is to follow the dynamics of lipids and lipid domains on the surface of living cells using the four available LBPs

Work environment: The applicant should feel comfortable to work in an interdisciplinary and international environment. The postdoctoral fellow will join the BioPhotonics Team headed by Prof. Yves Mely of the LBP (UMR 7021, CNRS/INSERM/University of Strasbourg, https://lbp.unistra.fr/ ) which offers a dynamic work environment. The laboratory is equipped with advanced spectroscopy and microscopy platforms (https://piq.unistra.fr/ ), a chemistry laboratory and rooms dedicated to cell culture.

The PostDoc will be part of a highly cooperative project including the team of Thomas Hirsch (University of Regensburg, Germany) specialized in synthesis and coating of UCNPs.

Contact: Applicants should email a CV including list of publications, a brief motivation letter and at least two recommendation letters to Prof. Yves Mély ([email protected] ) and Dr. Frédéric PRZYBILLA ([email protected] ) before 23/02/2024.

Ref: 1. Dukhno, O. et al. Time-dependent luminescence loss for individual upconversion nanoparticles upon dilution in aqueous solution. Nanoscale10, 15904–15910 (2018). 2. Targeted single-particle tracking with upconverting nanoparticles. https://www.researchsquare.com (2023) doi:10.21203/rs.3.rs-2924714/v1 .  3. Hullin-Matsuda, F., Murate, M. & Kobayashi, T. Protein probes to visualize sphingomyelin and ceramide phosphoethanolamine. Chemistry and Physics of Lipids216, 132–141 (2018).

Requirements

Research Field

Physics » Biophysics

Education Level

PhD or equivalent

Research Field

Chemistry » Physical chemistry

Education Level

PhD or equivalent

Research Field

Physics » Optics

Education Level

PhD or equivalent

Skills/Qualifications

We are looking for a highly motivated candidate with a background in physico-chemistry, biophysics or physics, and a strong interest in microscopy techniques and their applications in biology.

We value creativity and autonomy. Prior experience is expected in several of the following fields: microscopy, spectroscopy, fluorescence, upconversion luminescence, formulation/ functionalization of nanoparticles. Knowledge of Matlab or another programming language would be appreciated.

Specific Requirements

The applicant should feel comfortable to work in an interdisciplinary and international environment. The postdoctoral fellow will join the BioPhotonics Team headed by Prof. Yves Mely of the LBP (UMR 7021, CNRS/INSERM/University of Strasbourg, https://lbp.unistra.fr/ ) which offers a dynamic work environment. The laboratory is equipped with advanced spectroscopy and microscopy platforms (https://piq.unistra.fr/ ), a chemistry laboratory and rooms dedicated to cell culture.

The PostDoc will be part of a highly cooperative project including the team of Thomas Hirsch (University of Regensburg, Germany) specialized in synthesis and coating of UCNPs.

Languages

ENGLISH

Level

Excellent

Research Field

Chemistry » Physical chemistryPhysics » BiophysicsPhysics » Optics

Years of Research Experience

1 - 4

Additional Information
Work Location(s)

Number of offers available

1

Company/Institute

Laboratoire de Bioimagerie et Pathologies | UMR 7021 CNRS/Unistra

Country

France

City

Illkirch

Postal Code

67400

Street

74, route du Rhin

Geofield

Where to apply

E-mail

[email protected]

Contact

City

Strasbourg, Illkirch

Website

http://www-lbp.unistra.fr/

Street

74 route du Rhin

STATUS: EXPIRED