PhD candidate 'linking mTOR to deregulated GABA signalling in human IPSC-derived network models for neurodevelopmental epilepsy'

PhD candidate 'linking mTOR to deregulated GABA signalling in human IPSC-derived network models for neurodevelopmental epilepsy'

Published Deadline Location
2 Jul 15 Aug Nijmegen

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Job description

This PhD candidate position is available for a fixed term of 4 years to perform research in relation to mTORpathies and neurodevelopmental epilepsy at the Cognitive Neuroscience Department at the Radboudumc in Nijmegen. Epilepsy is a common neurological disease, affecting approximately 180,000 people in the Netherlands and treating childhood-onset genetic epilepsies remains challenging. Our overall aim is to gain mechanistic insight into the mTOR-dependent regulation of GABAergic networks in developmental epilepsies. We developed an in vitro model to investigate neuronal development, by differentiating hiPSCs into excitatory neurons (iNeurons) and forebrain organoids. We will use patient-derived hiPSCs CRIPSR/Cas9-edited lines carrying mTORpathy related mutations as well as TSC2 patients derived lines.

You will perform molecular (transcriptomic), structural (immunohistochemistry & quantitative morphometry) and functional phenotyping aiming for unravelling common molecular and cellular mechanisms of mTORpathies and developmental epilepsy. The functional phenotyping will employ measurements using state or the art high-density microelectrode arrays (MEAs) on 2-dimensional neuronal networks as well as on early developmental stages of brain organoids.

The project is part of an interdisciplinary collaboration with the Pathology Department at the Amsterdam UMC (E. Aronica group), connecting researchers with expertise in epilepsy, neuropathology and neurophysiology to elucidate the mechanisms underlying altered neuronal network function in epilepsy. The research will be located at the Cognitive Neuroscience Department (D. Schubert group) in strong collaboration with the Human Genetics department (N. Nadif Kasri group) and embedded in the Donders Institute for Brain, Cognition and Behaviour of the Radboud University Medical Center.

Our research team at the Radboud university medical center is renowned for its genetic, molecular and electrophysiological research in the field of neurological and neurodevelopmental disorders. Over the past years we have developed unique knowledge and resources, such as the human (patient) induced pluripotent stem cell lines, including the required experimental platforms for in-detail assessment of the derived human neuronal in-vitro network models.

Tasks and responsibilities
  • You will be responsible for generating isogenic hIPSC cell lines and develop brain organoid model for mTORpathies.
  • Designs and performs scientific research.
  • Works in a team with PhD students, scientists and clinicians.
  • Discusses, plans and performs research in a stimulating environment.
  • Works in a highly international research group and is willing to travel to other institutes within Europe.

Specifications

Radboud University Medical Center (Radboudumc)

Requirements

You have obtained an academic degree (MSc) in molecular life sciences, biomedical sciences or a related discipline. You also have a strong background in molecular and cellular neuroscience. Preferentially with basic experience in electrophysiology. You are highly motivated to work in an interdisciplinary environment at the cutting edge of science. You have e xperience with cell culture of primary neurons and induced pluripotent stem cells. In addition, excellent interpersonal and communication skills are essential, as is a willingness to work flexibly.

Conditions of employment

Fixed-term contract: 4 years.

Working at Radboud university medical center means that you are ahead of the curve and working together on the healthcare of the future. But there is more. Our secondary terms of employment are impressive. These are fully tailored to you thanks to our Employment Conditions Selection Model. At Radboud university medical center, you will be given trust, and you will take the responsibility to handle everything together. We provide annual courses, both professional and personal.
  • In addition to your monthly salary and an annual vacation allowance of 8%, you will receive an end-of-year bonus of 8.3%.
  • If you work irregular hours, you will receive an allowance.
  • As a full-time employee (36 hours per week), you are entitled to approximately 168 vacation hours (over 23 days) per year.
  • Radboud university medical center pays 70% of the pension premium. You pay the rest of the premium with your gross salary.
  • You get a discount on health insurance as well: you can take advantage of two group health insurance plans. UMC Zorgverzekering and CZ collectief.
In addition to our terms of employment, we also offer employees various other attractive facilities, such as childcare and sports facilities. Want to learn more? Take a look at the Cao UMC.

Employer

Radboudumc

The research project will be based at the department of Cognitive Neuroscience, in close collaboration with the department of Human genetics. We provide a stimulating work environment within a group of enthusiastic clinical and non-clinical researchers with a strong national and international research network. The departments house a range of top researchers in the areas of Genetics and Neurosciences. The departments both have a strong track record, with recent publications in high-impact journals (Science, Nature, Nature Genetics). The combined infrastructure is state-of-the-art including innovative genetic technologies (Next-Generation Sequencing, etc.), induced pluripotent stem cells (Nijmegen IPS Technology Center) and a wide range of cellular functional assays.

Research Institutes
At the moment there are more than 1,300 PhD candidates at our medical hospital. This number includes PhD candidates on our pay roll as well as external candidates (those employed somewhere else but researching on our premises).
  • Radboud Institute for Health Sciences: ± 700
  • Radboud Institute for Molecular Life Sciences: ± 400
  • Donders Center for Medical Neurosciences: ± 200
Read what it is like to do a PhD at the Radboud University Medical Center.

Radboudumc
Radboud university medical center is a university medical center for patient care, scientific research, and education in Nijmegen. Radboud university medical center strives to be at the forefront of shaping the healthcare of the future. We do this in a person-centered and innovative way, and in close collaboration with our network. We want to have a significant impact on healthcare. We want to improve with each passing day, continuously working towards better healthcare, research, and education. And gaining a better understanding of how diseases arise and how we can prevent, treat, and cure them, day in and day out. This way, every patient always receives the best healthcare, now and in the future. Because that is why we do what we do.

Read more about our strategy and what working at Radboud university medical center means. Our colleagues would be happy to tell you about it. #weareradboudumc

Specifications

  • PhD
  • Health
  • max. 36 hours per week
  • €2495—€3196 per month
  • University graduate
  • 141383-P753934-1

Employer

Radboud University Medical Center (Radboudumc)

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Location

Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen

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