PhD Position: Missing Link Aβ Exposure and Inhibitory Synaptic Defects

PhD Position:
Finding the Missing Link between Aβ Exposure and Inhibitory Synaptic Defects

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 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 and 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.

• You are a highly motivated, enthusiastic, critical, creative and team‑oriented young scientist with a particular interest in neuroscience.
• You have a Master's degree in life sciences, biology, biomedical sciences or a related discipline, and an interest in intracellular signalling and optical recording methods.
• Ideally, you have some experience in advanced microscopy and/or electrophysiology in living brain tissue and in programming (in Matlab or a similar environment), or are willing to learn.
• You take initiative and are eager to learn.
• You can work independently, but you also enjoy interacting within a group.
• You are fluent in English (written and spoken) and have good communication skills.
• You demonstrate integrity and positivity and motivate others to do the same.

• We will give you a temporary employment contract (1.0 FTE) of 1.5 years, after which your performance will be evaluated. If the evaluation is positive, your contract will be extended by 2.5 years (4‑year contract).
• You will receive a starting salary of €3,059 gross per month based on a 38‑hour working week, which will increase to €3,881 in the fourth year (salary scale P).
• You will receive an 8% holiday allowance and an 8.3% end‑of‑year bonus.
• You will receive extra days off. With full‑time employment, you can choose between 30 or 41 days of annual leave instead of the statutory 20.

Work and science require good employment practices. Radboud University's primary and secondary employment conditions reflect this. You can make arrangements for the best possible work‑life balance with flexible working hours, various leave arrangements and working from home. You are also able to compose part of your employment conditions yourself. For example, exchange income for extra leave days and receive a reimbursement for your sports membership.

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