Characterization of the aggregation and potential toxicity of the p3 peptide

INTRODUCTION

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. Neurotoxicity in AD is thought to initiate with the aggregation of the Alzheimer beta (Ab) peptide.

Ab is produced from the Amyloid Precursor Protein (APP) via a complex mechanism involving sequential cleavage by b- and g-secretase. This is called the amyloidogenic pathway. Alternatively, APP can be processed through cleavage by a- and g-secretase respectively which results in the release of the so-called p3 peptide, the non-amyloidogenic pathway. Current Alzheimer's disease therapy is often focused on inhibiting the amyloidogenic pathway, hence upregulating the activity of a-secretase. However, little is known about the aggregation or oligomerization behavior of the p3 peptide and whether it potentially induces toxic effects.

APP processing.png

PROJECT DESCRIPTION

This BSc project aims to characterize the aggregation and potential toxicity of the p3 peptide. You will learn a variety of biophysical and cell culture techniques to evaluate these characteristics. You will use A11 oligomer-specific antibody and ThT fluorescence to follow the oligomerization and fibrillization processes of the p3 peptide. Atomic Force Microscopy will be used to confirm the presence of fibrils, and can provide information on the structural characteristics of the formed fibrils. You will also explore the use of other assays to evaluate p3 aggregation such as size exclusion chromatography. Finally, the toxicity of the formed species will be assessed in the in cellulo facility.

The two questions this project focuses on are:

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Does the p3 peptide aggregate, and, if so, what is its mechanism?

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Are p3 peptides toxic to cells in culture?

The set up of this project is dual, consisting of a biophysical approach to describe aggregation and a biological part assessing toxicity. According to your background and personal interest one of both branches can be more emphasized.

MORE INFORMATION

Annelies Vandersteen, MSc, ir 

PhD student 

annelies.vandersteen@switch.vib-vub.be

http://switch.vub.ac.be/neurodegeneration

Phone +32 (0)26291924

Annelies is currently based at the Vrije Universiteit Brussel and will be at Universiteit Twente starting from June, 1st. The proposed project will be executed at Universiteit Twente. Dr. Kerensa Broersen will be located at Universiteit Twente from the 1st of March onwards and will be available for discussion on the project.