PhD position: Structural characterization of lipid-associated IAPP and Aβ Fibrils in Type 2 Diabetes and Alzheimer’s Disease (H/F)

Description du Poste

Sujet De Thèse

LipAgg Doctoral Network project
The LipAgg project (https://lipagg.eu/) seeks to unravel the structural complexities of amyloid protein-lipid aggregates and investigate their role in pathological aggregation, cellular toxicity, and intercellular spread. Focusing on key human amyloid proteins —amylin (IAPP), amyloid beta (Aβ), and α-synuclein (αS)—linked to type 2 diabetes (T2D), Alzheimer's disease (AD), and Parkinson’s disease (PD), respectively, the project builds on recent discoveries made by the consortium. These findings highlight the critical role of free lipids in membrane damage through the formation of stable lipid-amyloidogenic protein complexes, leading to the lipid-chaperone hypothesis.

LipAgg Doctoral Network program
The selected PhD candidate will participate in the EU-funded HORIZON-MSCA-DN-2024-01 project LipAgg. The LipAgg network brings together partners from 6 European countries and comprises 11 academic or research institutions and 12 industrial partners. The consortium is committed to delivering an outstanding training programme for 15 Doctoral Candidates (DCs) aimed at elucidating the role of lipids in the toxicity and propagation of protein aggregation.

Title: Structural characterization of lipid-associated IAPP and Aβ Fibrils in Type 2 Diabetes and Alzheimer’s Disease.

Objectives: The goal of this project is to determine the structures of both islet amyloid polypeptide (IAPP) and amyloid-β (Aβ) using cryo-electron microscopy (cryo-EM). Amyloid fibrils will first be characterized alone and then in the presence of specific free lipids and model membranes. Both conventional lipids (such as phosphatidylcholine and phosphatidylserine) and less conventional lipids will be selected in collaboration with 2 other doctoral candidates from the consortium (DC1 and DC3). Smaller aggregate species will also be investigated using electron microscopy, although at lower resolution due to their size and structural heterogeneity. All cryo-EM structural data will be correlated with toxicity assays performed by the doctoral candidate DC7.

Key words: amyloid forming proteins, lipid/protein interactions, cryo-electron microscopy, fluorescence

The Position
The Doctoral candidate key tasks will be to manage and carry out the assigned research project, participate in the LipAgg training and network activities, take PhD courses, write scientific articles and your PhD thesis, participate in national and international congresses and scientific meetings, undertake a research stay at an external research laboratory within the LipAgg network, and disseminate the obtained scientific results.

The expected start date is 1 September 2026.

Required documents
CV - including methodological skills
Motivation letter
Copy of Master’s degree (or proof of expected completion)
Master thesis (if available)
All academic transcripts
Contact information for at least two references

Recent representative publications of Dr. Lucie Khemtemourian and Dr. Gunnar Schröder

1. McCalpin SD, Khemtemourian L, Suladze S, Ivanova MI, Reif B, Ramamoorthy A. Zinc and pH Modulate the Ability of Insulin to Inhibit Aggregation of Islet Amyloid Polypeptide. Communications Biology, 2024, 7, 776. DOI.org/10.1038/s42003-024-06388-y.
2. Khemtemourian L, Fatafta H, Davion B, Lecomte S, Castano S and Strodel B. Structural dissection of the first events following membrane binding of the islet amyloid polypeptide. Frontiers in Molecular Biosciences, 2022, 9, 849979. DOI.10.3389/fmolb.2022.849979.
3. Hoffmann ARF, Saravanan MS, Lequin O, Killian JA, Khemtemourian L. A single mutation on the human amyloid polypeptide modulates fibril growth and affects the mechanism of amyloid-induced membrane damage. BBA-Biomembranes, 2018, 1860, 1783-92. DOI.10.1016/j.bbamem.2018.02.018
4. Frieg B, Han M, Giller K, Dienemann C, Riedel D, Becker S, Andreas LB, Griesinger C, Schröder GF. Cryo-EM structures of lipidic fibrils of amyloid-beta (1-40). Nat Commun. 2024, 15, 1297. DOI.10.1038/s41467-023-43822-x.
5. Röder C, Kupreichyk T, Gremer L, Schäfer LU, Pothula KR, Ravelli RBG, Willbold D, Hoyer W, Schröder GF. Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-beta fibrils. Nat Struct Mol Biol. 2020, 7, 660-667. DOI.10.1038/s41594-020-0442-4.

Votre Environnement de Travail

The ideal candidate for this position is a highly motivated and talented researcher holding a Master’s degree (MSc or equivalent) in Biophysics, Chemical Physics, Biochemistry or Structural Biology.

The candidate should enjoy the challenge of novel scientific concepts and have a highly motivated, persistent and result-driven attitude. The candidate should be able to work well both independently and in an interdisciplinary team.

Excellent oral and written communication skills in English are required. Strong organisational and planning skills are also necessary.

This position is subject to the mobility and eligibility rules of the Marie Skłodowska-Curie Actions. In particular, the candidate must not have resided or carried out their main activity (work, studies, etc.) in France for more than twelve months during the three years immediately prior to the recruitment date, unless as part of a procedure for obtaining refugee status under the Geneva Convention. At the date of recruitment, the candidate must be a Doctoral Candidate, i.e. in the first five years (full-time equivalent research experience) of their research career and must not have been awarded a doctoral degree.

Rémunération et avantages

Rémunération

gross salary of 3048 euros per month for the living allowance and of 710 euros per month for the Mobility

Congés et RTT annuels

44 jours

Pratique et Indemnisation du TT

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

À propos de l’offre

À propos du CNRS

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