Development of a workflow from immunopurification to microfluidic chip analysis of alpha synucl[...]

Institut de Chimie Physique/Université Paris Saclay/CNRS; Orsay; Sur place; EUR 20 000 - 40 000; Plein temps

Résumé du poste

Une institution académique en France recherche un candidat motivé ayant des solides connaissances en biochimie pour développer des protocoles de biomarqueurs liés à la maladie de Parkinson. Ce rôle nécessite un bon niveau d'anglais et une capacité à travailler en équipe, surtout dans un cadre inter-laboratoires.

Qualifications

• Solides connaissances en biochimie exigées.
• Fort niveau d'anglais requis.
• Capacité à travailler en équipe indispensable.

Responsabilités

• Développer un protocole de biomarqueur pour le diagnostic précoce de la maladie de Parkinson.
• Immunopurifier et analyser l'alpha-synucléine à l'aide de techniques avancées.

Connaissances

Connaissances en biochimie

Anglais

Travail en équipe

Connaissances en spectrométrie de masse

Description du poste

Description

The recent years have seen a rise of evidence interconnecting protein unfolding and structural pathologies. Indeed, misfolding and aggregation of diverse specific proteins and their accumulation as lethal amyloid in different organs is the hallmark feature in a group of chronic, degenerative diseases termed protein misfolding disorders (PMDs). PMDs include highly prevalent human illnesses such as Alzheimer’s (AD) [1] and Parkinson’s (PD) [2] diseases. Among them, prion diseases are unique because the pathology can be transmitted by a proteinaceous infectious agent, termed a prion, that induces disease by propagating protein misfolding and aggregation [3]. All misfolded proteins involved in PMDs like a-synuclein (a-syn) in PD share common properties, such as aggregation, seeding, and orderly propagating process [4-7]. Within this scope, we recently described new intrinsic properties of the prion protein conformational landscape with respect to several physio-chemical parameters such as protein concentration [8] as well as mutations [9]. It appears from these experiments that protein concentration and mutations modulate conformers abundances, a result that can be viewed as a marker of early events of neurodegenerative diseases. Similar results were obtained on a-synuclein, showing that changes in conformation abundances occurred with pH, protein concentration or the presence of an acetyl group in N-terminus. Spontaneous aggregation revealed the appearance of a truncated form, that is viewed as an early biomarker of Parkinson disease.

Our objective is to develop a workflow from immunopurification to microfluidic chip analysis of alpha synuclein to develop a conformational biomarker protocol using ion mobility and mass spectrometry for early diagnostic of Parkinson disease. The one-step microfluidic device is aim at immuno-purify, dialyze, concentrate alpha-synuclein from complex biological fluids ( cerebrospinal fluid, plasma, red blood cells) in one step to avoid extensive manipulation. Here the decisive and challenging innovation stands in the validation of the immunoprecipitation process that must not alter conformational properties of alpha synuclein and of the use of conformers variations as biomarkers of PD in biological

Profile

Le / la candidat-e devra avoir de solides connaissanes en biochimie, une forte motivation, un bon niveau d'anglais et la capacité de travailler en équipe. Des connaissances en spectrométrie de masse est un plus. Le trvail en équipe est très important dans la mesure ou le sujet est à cheval sur deux laboratoires.

Starting Date

• 02-02