PhD Position in Neurodevelopmental Disorders
Catholic University of Leuven
Belgium

 
Research in the Lab of Protein Phosphorylation and Proteomics (LPPP) focuses on the regulation of (patho)physiologic processes by reversible phosphorylation, an indispensable protein modification for control of cell signaling processes. Within this context, we are interested in human diseases characterized by dysfunctions of protein kinases and protein phosphatases, with a focus on protein kinase D (PKD) and protein phosphatase 2A (PP2A). Our research is both of fundamental and translational nature, and we have multiple clinical collaborations. Website: https://www.kuleuven.be/wieiswie/en/person/00015134

Project

Reversible protein phosphorylation is a majorly important post-translational modification involved in cell regulation and signaling. Dysfunctions of the kinases or phosphatases involved often result in human pathologies, including cancer, diabetes, immunologic and neurologic disorders. For more than 20 years, we have studied in our lab, the structure, function and regulation of Protein Phosphatase 2A (PP2A), the major family of Ser/Thr-specific phosphatases in most cells and tissues. Five years ago, in 2015, we discovered that inborn, de novo mutations in specific PP2A genes are the cause of a new genetic disorder, characterized by intellectual disability, (neuro)developmental delay, hypotonia, dysmorphic features, and sometimes epilepsy, autism, heart defects and brain abnormalities (Houge*,Haesen* et al. 2015; Reynhout*, Jansen* et al. 2019). Biochemical characterization of the variants revealed these mutations predominantly result in PP2A losses-of-function, although potential gains-of-function might not be excluded at this point. While PP2A shows high expression in brain and regulates a broad network of neuronal signaling cascades, it is currently not known which specific pathways are affected by these genetic PP2A alterations, or which brain areas might be dysfunctional. The aim of this project is to phenotypically characterize in depth different in vitro and in vivo models of this syndrome, including a neuronal cell model derived from human patient-derived iPCSs and a mouse model, in which the most recurrent PP2A mutation was introduced. These studies, coupled to extended biochemical assays to better understand the consequences of the mutation at the PP2A enzyme level, will provide the first patho-physiological insights into this new genetic disorder. These insights should eventually allow us to guide new therapeutic approaches to treat this disease and improve the general health of affected individuals.

Profile

-You obtained a Master degree in Biomedical Sciences, Medicine, Pharmacy, Biochemistry, Bioengineering, Biology, or related area, with excellent study results, and at least a ‘distinction’ during the Master years.

-You are passionate about scientific research, and motivated to pursue a PhD degree for at least 4 years.

-You are willing to work with animals (mice); possession of a FELASA B certificate and/or previous experience with mouse-related work is a strong plus.

-You can work independently, but are also a team player.

-You have an excellent knowledge of English, spoken and written.

Offer

-You can do state-of-the-art, innovative research into a new disease within the context of a dynamic team with more than 20 years of expertise in PP2A research.

-You will get an excellent guidance and supervision.

-You can collaborate with several other national and international research teams, allowing you to broaden your scientific knowledge and network.

-You can get in close contact with families and patients of this new PP2A-related syndrome.

-You will get a 1-year-PhD fellowship that is conditionally extendable up to 4 years; additional application for a personal PhD fellowship (e.g. FWO pre-doctoral fellowships) is strongly encouraged, and you will get every support to achieve this.

-In principle, the start date of the PhD is 1 Jan. 2021, but this is flexible in joint consultation with your supervisor.

Interested?

Send a personal motivation letter, including CV and contact details of at least one reference to the supervisor of this project, Prof. Veerle Janssens (veerle.janssens@kuleuven.be), before 15th September 2020.

You can also contact Saar Reynhout (sara.reynhout@kuleuven.be), a previous PhD student on the topic, for more information.

You can apply for this job no later than September 30, 2020 via the
KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.
  • Employment percentage: Voltijds
  • Location: Leuven
  • Apply before: September 30, 2020
  • Tags: Cellulaire en Moleculaire Geneeskunde


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