Synthesis of post-translationally modified peptide fragments in Alzheimer’s Disease

Depuis le 1er janvier 2020, l’Equipe Chimie Biologique de CY Cergy Paris Université a intégré L’UMR CNRS BioCIS (Biomolécules : Conception, Isolement, Synthèse) de la faculté de pharmacie de l’Université Paris Saclay.
L’équipe Chimie Biologique est située sur le site universitaire de CY Cergy Paris Université de Neuville/Oise.
L’équipe regroupe des chercheurs sur la thématique générale de la chimie orientée vers les sciences de la vie. Elle étudie la synthèse, la caractérisation et l’évaluation de biomolécules, ainsi que la mise au point de nouvelles méthodologies de synthèse.
Nous sommes spécialisés dans la chimie des acides aminés modifiés et des peptides notamment fluorés, des glycosides, glycopeptides, pour des applications dans le domaine de la chimie biologique et de la chimie médicinale.
Les compétences des membres de l'équipe comprennent entre autres la chimie des composés organofluorés et des glycosides, la chimie organométallique, la synthèse asymétrique, la synthèse sur surface solide des peptides, les analyses structurales et biophysiques. 
 

This masters level internship involves the synthesis of large peptides/ protein fragments to help further understand the misfolding of proteins in neurodegenerative disease. We are specifically looking at Tauopathies such as Alzheimer’s Disease. The project benefits from a collaboration with the CPCV laboratory at Sorbonne University.

                                                                                                           Abstract:  Tau, along with amyloid beta, is one of two protein aggregates that underpin our current understanding of Alzheimer’s disease (AD). While Aβ is primarily implicated in AD, Tau is involved in over twenty other neurodegenerative diseases known as tauopathies in which misfolded Tau is found in neuronal fibrils. Emerging post-mortem cryo-EM images of pathological Tau fibrils strongly suggests that the particular protein fold observed for each tauopathy may be the defining criterion for that disease. However, the different biological “switches” that send Tau down a specific disease pathway and fold in vivo remain to be clearly defined. Post-translational modification (PTM), and in particular phosphorylation of Tau is known to be involved in AD pathology. The main objective of this internship is to synthesize discrete fragments of the Tau protein that incorporate defined pathological post-translational modifications (PTMs).

Project: The project will include both manual and automated microwave-assisted SPPS to generated post-translationally modified peptides which will be subject to chemical ligation with our collaborators at Sorbonne University. The synthetic fragments will be subjected to aggregation assays and monitored by Fluorescence assay, Circular Dichroism and Infrared spectroscopy. The most interesting peptides will be characterized structurally via NMR and/or cryo-EM.

We are looking for a Candidate with experience in organic chemistry and/ or peptide chemistry. Ideally with an interest in their application to biological systems.