PhD Position in Ecology

Overview

Are you an enthusiastic young scientist with a Master’s degree in a neuroscience-related field? And would you like to figure out how synaptic defects occur in early Alzheimer’s disease? If so, then you have a part to play as a PhD candidate in our research team. Put your ideas to the test at our green campus and push your boundaries in an internationally friendly environment.

One of the main reasons that there is no treatment for Alzheimer’s disease (AD) is that cellular mechanisms of the disease onset and progression are not well understood. AD is a slowly progressing disease. Long before cognitive and behavioural symptoms occur, the level of Aβ oligomers in the brain are slowly rising, causing synaptic defects and network hyperexcitability. Hyperexcitable networks have been widely observed in AD patients and can be reproduced in a wide range of AD mouse models with progressing Aβ levels. Preventing or delaying hyperexcitability can delay or prevent cognitive impairments, indicating that hyperexcitability in early AD stages is a crucial factor in the progression of the disease.

An increasing number of studies (including from our lab: Ruiter et al, J Alz Dis 2020) are demonstrating that inhibitory circuits are specifically vulnerable to Aβ in the brain, which could underlie the enhanced excitability in neuronal networks observed at early AD stages. However, the molecular mechanism of the vulnerability of inhibitory synapses is not well understood.

Research Project

Research in the Wierenga lab focuses on the formation and plasticity of inhibitory synapses. In this project, you will use a combination of:

• Single-cell electrophysiology
• Advanced microscopy techniques
• Novel biosensors

to characterise synaptic defects at inhibitory synapses in cultured brain slices that have been exposed to amyloid β oligomers.

You will use the novel iGABASnFR2 sensors in slices from transgenic mice to monitor Aβ-mediated alterations in GABA release at specific subtypes of inhibitory synapses. In parallel, you will monitor molecular and electrophysiological changes to assess the involvement of specific signalling pathways.

Your teaching load may be up to 10% of your working time.