The first stage of Alzheimer’s disease (AD) is characterized by Aβ-induced hyperexcitability and impaired synapse function. We recently found that Aβ exposure impaired GABA release at inhibitory synapses in the hippocampus, while synapse numbers and excitatory synaptic currents remained unchanged. Even further, we found that Aβ targets preferentially dendritic inhibitory synapses more than perisomatic inhibitory synapses . These data suggest that Aβ differentially affects excitatory and different inhibitory synapses and add to the emerging notion that, apart from the well-studied effects on postsynaptic function, Aβ also severely affects presynaptic processes.
The aim of this PhD project is to provide insight in the Aβ-induced changes in presynaptic nanostructure and function and reveal why different synapse types have differential sensitivity to Aβ. In this project, you will investigate presynaptic nanostructure using super-resolution imaging on endogenous proteins using a recently developed CRISPR/Cas9 genome editing toolbox , and a combination of electrophysiological recordings and advanced imaging to correlate changes in protein distribution with effects of Aβ oligomers on presynaptic function.
This is a collaborative project, led by Dr. Corette Wierenga and Dr. Harold MacGillavry.
Ruiter,.. Wierenga CJ (2020) J Alzheimer’s Dis 78:951–
Willems, … MacGillavry (2020) PLoS Biol 18: e3000665
Qualifications
We are looking for a motivated PhD candidate with strong analytical and experimental skills and a deep interest in neuroscience. Apart from this we would like you to bring the following qualifications and characteristics:
- You have a Master's degree with a solid background in neurobiology or a related field of life sciences and an interest in neurodegenerative diseases.
- Ideally you have prior experience with one or more of the key experimental approaches required for the project: whole-cell patch clamp electrophysiology, fluorescence microscopy and molecular biology. The willingness to learn and combine these techniques is also much appreciated.
- You are fluent in English (written and spoken) and have good communication skills.
Offer
- a position for four years;
- a full-time gross salary starting at €2,443 in the first year and increasing to €3,122 in year four (scale P Collective Labour Agreement Dutch Universities);
- 8% holiday bonus and 8.3% end-of-year bonus;
- a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities.
In addition to the employment conditions laid down in the cao for Dutch Universities, Utrecht University has a number of its own arrangements. For example, there are agreements on professional development, leave arrangements and sports. We also give you the opportunity to expand your terms of employment via the Employment Conditions Selection Model. This is how we like to encourage you to continue to grow.
More information about working at the Faculty of Science can be found here .
About the organisation
This is a collaborative project between the groups of Dr. Wierenga and Dr. MacGillavry , who are embedded within the Division of Cell biology, Neurobiology and Biophysics of the Biology Department at the Faculty of Science of Utrecht University. The division aims to gain insight into basic cellular processes and in this way provide a mechanistic basis for devising therapies for cancer, metabolic and neurological diseases. Research topics of the division include: mechanisms underlying cytoskeletal dynamics, membrane transport and signaling pathways that underlie cell proliferation and differentiation, neuronal development and synaptic plasticity. We investigate cellular processes at a broad range of levels, from single molecules and protein networks to cells, tissues, and whole organisms.
At the Faculty of Science , there are 6 departments to make a fundamental connection with: Biology, Chemistry, Information and Computing Sciences, Mathematics, Pharmaceutical Sciences. and Physics. Each of these is made up of distinct institutes that work together to focus on answering some of humanity’s most pressing problems. More fundamental still are the individual research groups – the building blocks of our ambitious scientific projects. Find out more about us .
Utrecht University is a friendly and ambitious university at the heart of an ancient city. We love to welcome new scientists to our city – a thriving cultural hub that is consistently rated as one of the world’s happiest cities. We are renowned for our innovative interdisciplinary research and our emphasis on inspirational research and excellent education. We are equally well-known for our familiar atmosphere and the can-do attitude of our people. This fundamental connection attracts researchers, professors and PhD candidates from all over the globe, making both the university and the Faculty of Science a vibrant international and wonderfully diverse community.
Additional information
Additional information regarding the vacancy can be obtained from:
Dr. Corette Wierenga , via c.j.wierenga@uu.nl , or Dr. Harold MacGillavry , via h.d.macgillavry@uu.nl .
Do you have a question about the application procedure? Please send an email to science.recruitment@uu.nl .
Apply
Everyone deserves to feel at home at our university. We welcome employees with a wide variety of backgrounds and perspectives. If you have the expertise and the experience to excel in this role, then simply respond via the “Apply now” button! Please enclose:
- your letter of motivation;
- your curriculum vitae;
If this specific opportunity isn’t for you, but you know someone who may be interested, please forward this vacancy to them.
Please note: Due to the current situation regarding the Coronavirus (COVID-19) the process of selection and interviews is subject to change. Initial interviews will most likely be conducted online.
Some connections are fundamental – Be one of them
The application deadline is 6 March 2022.
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