About the project
Atypical brain connectivity is a major contributor to the pathophysiology of neurodevelopmental disorders, including autism spectrum disorders (ASD). TAOK2 is one of several genes in the 16p11.2 microdeletion region, which is affected in about 1% of all ASD patients.
Recent behavioral analysis in a Taok2 knockout (KO) mouse model revealed impairments in cognition, anxiety and social interaction (Richter et al. Mol Psych 2018). These mice display hallmarks of 16p11.2 microdeletion patients including increased brain size, deficits in neuronal morphology, aberrant neural connectivity in multiple brain regions and reduced neurotransmission.
Moreover, TAOK2 is functionally linked to several additional ASD risk genes including MYOVa and Shank3, suggesting that TAOK2 is a central player regulating neuronal development and function. Based on the critical role TAOK2 might play in 16p11.2 patients and its function as a major hub for ASD-linked genes, it is an excellent candidate to identify novel treatment strategies that target this pathway.
This project focuses on quantitative analysis of the synaptic proteome in Taok2 KO and 16p11.2 deletion mouse models using in vivo metabolic labeling (Savas et al. Neuron 2015) and RNA sequencing approaches to elucidate the TAOK2 interaction network. The functional relevance of identified candidate TAOK2 interactors will be functionally tested in vivo.
About the lab
This project is part of an ERANET NEURON-funded consortium project on the role of TAOK2 and its downstream pathway as critical effectors of autism spectrum disorders in 16p11.2 microdeletion patients.
You will make use of quantitative proteome analysis in multiple mouse models of ASDs to generate TAO2 interaction maps and elucidate the molecular basis of neuronal dysfunction and impaired synaptic maturation in Taok2 KO and 16p11.2 deletion mice. Proteomics analyses will be complemented with RNA sequencing analyses from the same mouse models.
The role of identified TAOK2 candidate interacting genes will subsequently be tested in vivo, using mouse genetics and viral vector approaches, in combination with (ultra)structural and functional analysis of synaptic connectivity.
- Rice et al. Science (2019). 363(6423)
- Condomitti et al. Neuron (2018). 100:201-215
- Schroeder et al. Neuron (2018). 99:329-344
- De Wit and Ghosh. Nat Rev Neurosci (2016). 17:22-35
- Savas et al. Neuron (2015). 87:764-780
We are seeking a highly motivated, independent, enthusiastic, critical and creative individual to join our team. The candidate should have a strong interest in synapse biology and developmental neurobiology.
- PhD in neurobiology (molecular, cellular, developmental, systems) or related disciplines
- A solid publication record with first-author research publication(s) in peer-reviewed international journals
- Team player
Desirable but not required
- Prior experience with bioinformatics analysis is a plus
- Prior experience with mouse neurobiology is a plus
- A versatile and challenging job in a vibrant, world-class research environment operating at an international level
- State of the art research facilities
- A dedicated training program to broaden your expertise and enhance your skill set
- A project that is part of an international consortium with partners in Germany and Canada
- A competitive compensation package based on expertise and experience
- Financial support for at least 2 years. The successful candidate is encouraged to obtain a personal fellowship (Marie-Curie, HFSP, EMBO, or national funding organizations)
- Starting Date: as soon as possible
How to apply?
For more information contact Joris de Wit. Please complete the online application procedure and include a detailed CV incl. list of publications, a motivation letter, and the contact information of three referees.