Job ID: 64319

PhD project on developing anti-sense oligonucleotide approaches for neurodevelopmental disorder by combining largescale molecular and bioinformatic datasets’

Position: Ph.D. Student

Deadline: 15 January 2022

Employment Start Date: 1 April 2022

Contract Length: 4 years

City: Nijmegen

Country: Netherlands

Institution: Radboud University Medical center

Department: Human genetics

Description:

This PhD studentship position is available for a fixed term of 4 years to perform research on the development of anti-sense oligonucleotide (ASO) therapy for neurodevelopmental disorders at the Human Genetics Department at the Radboudumc in Nijmegen.

Approximately 1% of children are born with severe neurodevelopmental disorders (NDDs) for which there is currently no disease-modifying therapy. However, because NDDs are frequently caused by identifiable pathogenic mutations, a unique therapeutic opportunity has emerged from recent developments in molecular biology, with the potential to revolutionize the treatment of this group of disorders. 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 to model several NDDs that are amenable for ASO therapy. The candidate will help with the development ASO strategies, using molecular datasets in combination with bioinformatics tools, and will be involved in testing ASOs at the molecular and functional level. 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 within a consortium financed by the ZonMW PSIDER program. The candidate will closely interact with research groups of Prof. Elgersma, Prof. Kushner and dr. de Vrij at Erasmus MC (Rotterdam), as well as Prof. Aartsma-Rus and  Prof. van Roon-Mom at LUMC (Leiden). In Nijmegen the research will be located at the Human genetics Department (collaboration between PI groups of Vissers and Nadif Kasri) 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 availability of large molecular datasets on patients with NDDs, and 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.

 

 

  • The PhD student will be responsible for developing novel therapeutical strategies for selected neurodevelopmental disorders, using ASO technology.
  • 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.

 

  1. Profile
  • Academic degree (MSc) in molecular life sciences, biomedical sciences or a related discipline.
  • A strong background in bioinformatics
  • Has affinity with cellular and molecular biology
  • Highly motivated to work in an interdisciplinary environment at the cutting edge of science
  • Excellent interpersonal and communication skills are essential, as is a willingness to work flexibly

Information about the vacancy can be obtained from Prof. dr. Lisenka Vissers (Lisenka.Vissers@radboudumc.nl)  and  dr. Nael Nadif Kasri (n.nadif@donders.ru.nl) (This e-mail addresses are to be used for information purposes only