LipAgg European Doctoral Network

We are delighted to welcome our 15 PhD students to the LipAgg European Doctoral Network as they begin bringing the LipAgg project to life.

The LipAgg project aims to elucidate the structural and functional roles of amyloid protein–lipid aggregates in pathological processes such as aggregation, cellular toxicity, and intercellular spread.

It focuses on key amyloidogenic proteins : amylin (IAPP), amyloid beta (Aβ), and α-synuclein (αS). The project investigates the lipid-chaperone hypothesis, which highlights the role of free lipids in promoting membrane damage through stable protein–lipid complexes. LipAgg will address critical molecular mechanisms underlying amyloid toxicity, including oligomer toxicity, membrane interactions, and aggregate propagation.

Combining advanced biophysical, structural, chemical and cellular approaches, the project ultimately seeks to identify strategies to prevent amyloid-related damage and improve therapeutic perspectives.

LipAgg Doctoral Network projects

LipAgg fellows

DC1 Emilie FONTAINE

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Project : xxx

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DC2 project - Applications closed

This project aims at establishing a reproducible protocol to generate αS-lipid complexes made from recombinant αS and near physiological vesicle preparations, the characterisation of their stability using DSC and ITC and their structure at the near atomic resolution using solid state NMR.

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Supervisor : Christian Griesinger – Director, Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Co-supervisor : Céline Galvagnion – Associate Professor of Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark

DC3 project - Applications closed

This project focus on the characterization of the islet amyloid polypeptide (IAPP)/lipid complexes formed with lipid mixtures of varying composition, ranging from phospholipids to free fatty acids. The candidate will isolate β-cells from pancreatic islets and determine their lipid composition using lipidomics (in collaboration with a mass spectrometry centre). IAPP fibril formation and structure will be investigated using biophysical techniques, mainly fluorescence spectroscopy, circular dichroism, and microscopy.

Finally, the candidate will study the insertion of IAPP–lipid complexes into lipid membranes using Resonance Raman Spectroscopy, as well as perform kinetic and thermodynamic measurements. This will be done in the presence and absence of peptidomimetic inhibitors made by DC11.

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Supervisor : Carmelo La Rosa – Associate Professor of Physical Chemistry, Department of Chemical Sciences, University of Catania, Italy
Co-supervisor : Lucie Khemtemourain – Research Director, Laboratory of Chemistry and Biology of Membranes and Nano-objects, Spectroscopy and Imaging of Membrane-Active Peptides Team, CNRS / Bordeaux INP / University of Bordeaux, France

DC4 project - Applications closed

This project leverages advanced molecular simulations to quantify the binding affinity of the amyloidogenic proteins IAPP and α-Synuclein (αS) to diverse lipid environments. Our goal is to elucidate how lipid interactions dictate the structural transformation and aggregation dynamics of these proteins—processes central to Type 2 Diabetes and Parkinson’s Disease. Building on these insights, we will utilize a computer-aided drug design (CADD) toolbox to develop peptidomimetic inhibitors targeting key IAPP/αS-lipid binding hotspots.

As part of a highly collaborative effort within the LipAgg network, the successful candidate (DC4) will contribute to both the rational design and the targeted chemical synthesis of these novel ligands, preparing them for experimental validation across our consortium.

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Supervisor : Birgit Strodel – Professor, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Germany
Co-supervisor: Sandrine Ongeri – Professor of Therapeutic Chemistry, FluoPEPIT/BioCIS Team, Université Paris-Saclay / CNRS, France

DC5 project - Applications closed

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 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 DC7.

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Supervisor: Lucie Khemtemourain – Research Director, Laboratory of Chemistry and Biology of Membranes and Nano-objects, Spectroscopy and Imaging of Membrane-Active Peptides Team, CNRS / Bordeaux INP / University of Bordeaux, France
Co-supervisor: Gunnar F. Schröder – Professor, Molecular Structure and Biophysics Group, Ernst-Ruska Centre for Microscopy and Spectroscopy with Electrons, Forschungszentrum Jülich, Germany

DC6 project - Applications closed

The project aims to characterize the islet amyloid polypeptide (IAPP)/lipids complexes by NMR and to determination their structure at the near atomic resolution. Structural characterization of the IAPP fibrils grown in the presence of the Amyloid Protein-Lipid (AP-L) complexes will be done using NMR and compared to the structure obtained with cryo-EM (DC5). IAPP fibril formation kinetics in the absence and presence of AP-L will be studied as well as the incorporation of the AP-L into model membranes.

The Doctorate Candidate will also investigate membrane damages and/or perturbations associated with IAPP-lipid complex binding using fluorescence leaking assay and ²H and ³¹P-NMR. All NMR structural data will be correlated with toxicity assays performed by DC7.

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Supervisor: Christian Griesinger – Director, Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
Co-supervisor: Lucie Khemtemourain – Research Director, Laboratory of Chemistry and Biology of Membranes and Nano-objects, Spectroscopy and Imaging of Membrane-Active Peptides Team, CNRS / Bordeaux INP / University of Bordeaux, France

DC7 project - Applications closed

The Doctorat Candidate (DC) enrolled in this position, will identify mechanisms by which astrocytes spread Amyloid Protein-Lipid (AP-L) complexes and study if the AP-Ls induce astrocytic stress responses that affect their interplay with neurons. The candidate will expose cultures of human iPCS-derived astrocytes to fluorescently labelled AP-L complexes and analyze how the cells accumulate and spread the complexes over time using live cell imaging, immunocytochemistry, ELISA, Western blot, electron microscopy and other techniques.

Moreover, the DC will isolate deposits of amyloid complexes from human astrocytes and determination of their lipid composition. Moreover, the DC will isolate deposits of amyloid complexes from human astrocytes for DC10.

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Supervisor: Anna Erlandsson – Professor, Department of Public Health and Caring Sciences; Molecular Geriatrics / Rudbeck Laboratory, Sweden
Co-supervisor: Lucie Khemtemourain – Research Director, Laboratory of Chemistry and Biology of Membranes and Nano-objects, Spectroscopy and Imaging of Membrane-Active Peptides Team, CNRS / Bordeaux INP / University of Bordeaux, France

DC8 project - Applications closed

The DC enrolled in this position, will synthesize peptide mimics to modulate the pathological α-Synuclein protein aggregation as well as α-Synuclein/lipids interaction. The DC will be involved in the synthesis of unnatural scaffolds, i.e. non-natural amino acids and of peptide mimics, designed according to the results of the structural biology results of the consortium.

The DC will also perform conformational studies using NMR techniques, and will be involved in some biophysical and biochemical evaluations of the activity and the interaction of the prepared compounds with α-Synuclein or with lipids.

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Supervisor: Sandrine Ongeri – Professor of Therapeutic Chemistry, FluoPEPIT/BioCIS Team, Université Paris-Saclay / CNRS, France
Co-supervisor: Birgit Strodel – Professor, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Germany

DC9 project - Applications closed

This research project consists in investigating the cellular toxicity of AP-L complexes (αS, Aβ and IAPP) in pancreatic cells and iPSC-derived neurons. The Aβ-L, αS-L and IAPP-L complexes formed in vitro will be provided by DC1, DC2 and DC3, respectively. IAPP-L complexes isolated from pancreatic islets will be provided by DC3. iPSC from healthy controls and patients will be differentiated into dopaminergic ventral midbrain neurons.

The cellular toxicity of the AP-L will be assessed using Propidium Iodide (PI) cell death and TUNNEL assay, MTT, ROS analysis, ICC and Seahorse assays and compared to that of lipid-free AP complexes. The influence of AP-L inhibitors on cell toxicity will also be investigated using the inhibitors designed by DC8 and DC11.

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Supervisor: Céline Galvagnion – Associate Professor of Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark
Co-supervisor: Anna Erlandsson – Professor, Department of Public Health and Caring Sciences; Molecular Geriatrics / Rudbeck Laboratory, Sweden

DC10 project - Applications closed

This project aims at isolating αS-L complexes from neuronal models, to identify their lipid composition and seeding capacities in the test tube. The capacity of ex-cellulo isolated and in vitro prepared (in collaboration with DC2) αS-L complexes to seed the aggregation of αS in the test tube will be characterised using standard Thioflavin-T assays. Moreover, the PhD student will investigate membrane damages and/or perturbations associated with αS-L complex binding using RRS and fluorescence leaking assays during his/her stay at UNICT.

The effect of inhibitors on the membrane damaged and/or perturbations caused by these αS-L complexes as well as their seeding capacity in vitro and in cells will also be investigated in collaboration with DC8.

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Supervisor: Céline Galvagnion – Associate Professor of Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark
Co-supervisor: Carmelo La Rosa – Associate Professor of Physical Chemistry, Department of Chemical Sciences, University of Catania, Italy

DC11 project - Applications closed

The DC enrolled in this position, will synthesize peptide mimics to modulate the pathological Aβ-lipid and IAPP-lipid interaction. The DC will be involved in the synthesis of unnatural scaffolds, i.e. non-natural AAs and of peptide mimics, designed according to the results of the structural biology results of the consortium.

The DC will also perform conformational studies using NMR techniques, and will be involved in some biophysical and biochemical evaluations of the activity and of the influence of the prepared compounds on Aβ/lipid effects.

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Supervisor: Sandrine Ongeri – Professor of Therapeutic Chemistry, FluoPEPIT/BioCIS Team, Université Paris-Saclay / CNRS, France
Co-supervisor: Carmelo La Rosa – Associate Professor of Physical Chemistry, Department of Chemical Sciences, University of Catania, Italy

DC12 project - Applications closed

This research project aims at studying the seeding capacity of AP-L in pancreatic and iPSC-derived neurons. The capacity of ex-cellulo isolated (in collaboration with DC3, DC7 and DC10) and in vitro prepared (in collaboration with DC1, DC2, DC3) AP-L complexes to seed the aggregation of αS, Aβ and IAPP in pancreatic cells and/or iPSC-derived neuronal cells will be investigated using confocal microscopy.

Finally, the potential inhibitory effect of small molecules and peptidomimetics on in cellulo protein aggregation will be studied (in collaboration with DC4 and DC8).

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Main host : Céline Galvagnion – Associate Professor of Molecular and Cellular Pharmacology, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark
Second host : Anna Erlandsson – Professor, Department of Public Health and Caring Sciences; Molecular Geriatrics / Rudbeck Laboratory, Sweden

DC13 project - Applications closed

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This project aims at characterizing the aggregation state of amyloid proteins Aβ and IAPP complexed with lipid membranes using FTIR, EPR and NMR spectroscopy. The dynamical properties will be studied by measuring membrane fluidity and order parameters using EPR with spin labelled lipids or site directed spin labelled Aβ.

The lipid/proteins contacts will be determined by NMR spectroscopy. The composition of the model membranes investigated will be designed according to the protocols established by research partners (mainly DC1).

Application procedure:

1. Register

Create your account via Menu → Registration and complete all required personal information.

2. Choose the call

Select the call under the PhD course in Physical, Chemical and Materials Sciences and Technologies (MSCA LIPAGG Project).

3. Upload Your Documents

Submit all required supporting documents listed in Annex A of the Call (pages 12–16).

https://unical.portaleamministrazionetrasparente.it/moduli/downloadFile.php?file=oggetto_allegati/261349520342902150O__Odr_564_bando_dottorato_agg_unical_lipagg_stfcm_msca_xli_en.pdf

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Supervisor: Rita Guzzi – Associate Professor of Applied Physics, University of Calabria, Italy
Co-supervisor: Christian Griesinger – Director, Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

DC14 project - Applications closed

How do complexes formed between the amyloid proteins (Aβ, IAPP, and αS) and lipids)—referred to as AP-L complexes—penetrate and destabilize cell membranes? This project aims to decode the reciprocal dynamics between these toxic AP-L complexes and the lipid membrane environment. Using enhanced molecular simulation techniques, the successful candidate (DC14) will capture the high-resolution “insertion” events that trigger membrane failure.

A unique strength of this role is the tight integration of computational modeling with experimental EPR spectroscopy, providing a comprehensive assessment of lipid bilayer integrity.

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Supervisor: Birgit Strodel – Professor, Institute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, Germany
Co-supervisor: Rita Guzzi – Associate Professor of Applied Physics, University of Calabria, Italy

DC15 project - Applications closed

This PhD project studies how alpha-synuclein aggregates in the presence of lipids, which is relevant for example to Parkinson’s disease. High-resolution structures of lipidic α-synuclein fibrils will be determined using cryo-electron microscopy in the presence of aggregation inhibitors, with the aim to characterize how different inhibitors change the fibril structure.

The structural data will guide the design of new aggregation inhibitors, and the results will be linked to cellular toxicity. Computational modelling and peptide docking to alpha-synuclein structures to improve inhibitor binding. The project also supports related amyloid-β studies and includes collaboration on inhibitor design and synthesis.

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Supervisor: Gunnar F. Schröder – Professor, Molecular Structure and Biophysics Group, Ernst-Ruska Centre for Microscopy and Spectroscopy with Electrons, Forschungszentrum Jülich, Germany
Co-supervisor: Sandrine Ongeri – Professor of Therapeutic Chemistry, FluoPEPIT/BioCIS Team, Université Paris-Saclay / CNRS, France

We are delighted to welcome our 15 PhD students to the LipAgg European Doctoral Network as they begin bringing the LipAgg project to life.

LipAgg Doctoral Network projects

LipAgg fellows

Emilie Fontaine

Emilie Fontaine

DC1 Emilie FONTAINE

Project : xxx

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DC2 project - Applications closed

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DC3 project - Applications closed

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DC4 project - Applications closed

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DC5 project - Applications closed

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DC6 project - Applications closed

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DC7 project - Applications closed

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DC8 project - Applications closed

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DC9 project - Applications closed

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DC10 project - Applications closed

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DC11 project - Applications closed

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DC12 project - Applications closed

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DC13 project - Applications closed

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2. Choose the call

Select the call under the PhD course in Physical, Chemical and Materials Sciences and Technologies (MSCA LIPAGG Project).

3. Upload Your Documents

Partner:

Host PI:

DC14 project - Applications closed

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DC15 project - Applications closed

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Guiding principles and recommendations

Biography : Lucie Khemtemourian