Description du sujet de thèse

Peptide self-assembly is a feature of increasingly common diseases, including type 2 diabetes (T2D) and Alzheimer's disease (AD). These diseases involve the formation of amyloid fibres, either from amylin peptide (T2D) or from Aβ (AD). The imaging detection of these fibres is important both for diagnosis and for a better understanding of the molecular mechanisms of these diseases. Despite the large number of imaging probes described for the detection of amyloid fibres, none has so far shown selectivity for amylin-type amyloids over Aβ-type amyloids. As more and more evidence suggests a link between T2D and AD, the selective detection of amylin and Aβ amyloids becomes important. It is within this framework that the research proposed for this doctoral project takes place.
Imaging probes, bi-functional compounds containing a fibre targeting unit and a unit based on a Ln complex for MRI (magnetic resonance imaging) will be synthesised and characterised by our collaborators (CBM, Orléans).

In the Laboratoire de Chimie de Coordination (LCC), and within the ALAMBIC team, the subject will be articulated around two axes:
(i) Study of the self-assembly process of amylin and Aβ peptides, and their co-assembly.
(ii) Study of the interaction of probes with amyloids, and evaluation of the selectivity for amylin or Aβ fibres.

The technical and scientific environment of the laboratory and the host team is of high quality. The PhD student will be trained in advanced spectroscopic techniques such as NMR (paramagnetic), UV-Vis and circular dichroism, fluorescence and imaging microscopies.

Contexte de travail

The work will mainly be carried out at the CNRS Coordination Chemistry Laboratory (UPR 8241) in the team "ALAMBIC: Alzheimer, amyloids and bioinorganic chemistry" led by Dr. Christelle Hureau in the framework of a collaborative ANR involving two other partners (ANR MASAI). The project will benefit from the infrastructures of the team, the host laboratory (Laboratoire de Chimie de Coordination, UPR 8241) and the platforms available in Toulouse (Institut de Chimie de Toulouse).

Contraintes et risques

Handling of chemicals.

Informations complémentaires

In addition to the response via the CNRS portal, the applicant is asked to send a CV and a covering letter including the contact details of one or two referees to christelle.hureau@lcc-toulouse.fr and genevieve.pratviel@lcc-toulouse.fr