Doctoral Candidate Position 3 - University of Groningen the Netherlands

Activation and function of LRRK2 in macrophages

Application form

Description of project

Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of dopaminergic neurons in the brain. Mutations in Leucine-rich repeat kinase 2 (LRRK2) are so far the most frequent cause of late-onset and idiopathic PD. Furthermore, recent data suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in PD pathogenesis. LRRK2 PD-associated mutations result in increased α-synuclein aggregates, mitochondrial dysfunction and neuroinflammation. However, the role of LRRK2 in immunity is still not well understood. This PhD project aims to investigate the role of LRRK2 in macrophages and its contribution to PD pathophysiology.
Using targeted biochemical approaches, this project will determine how α-synuclein results in LRRK2 activation in microglia, peripheral monocytes, monocyte-derived macrophages. Moreover, LRRK2 substrates will be identified with phosphoproteomics. The influence of LRRK2 PD mutations on phagosome maturation, lysosomal functioning and mitochondrial metabolism will be tested with state-of-the art microscopy and molecular approaches. Finally, we will test how our novel allosteric LRRK2 inhibitors influence the inflammatory response in vitro in cultured immune cells and in vivo in murine PD models.

Required selection criteria

Preferred selection criteria

Specific Requirements

Benefits

Eligibility criteria

The University of Groningen strives to be a university in which students and staff are respected and feel at home, regardless of differences in background, experiences, perspectives, and identities. We believe that working on our core values of inclusion and equality are a joint responsibility and we are constructively working on creating a socially safe environment. Diversity among students and staff members enriches academic debate and contributes to the quality of our teaching and research. We therefore invite applicants from underrepresented groups in particular to apply. For more information, see also our diversity policy webpage.
Our selection procedure follows the guidelines of the Recruitment code (NVP) and European Commission's European Code of Conduct for recruitment of researchers.

Selection process

The application and supporting documentation to be used as the basis for the assessment must be in English. Applications should include:

If all, or parts, of your education have been completed abroad, we also ask you to attach documentation of the scope and quality of your entire education, both bachelor's and master's education, in addition to other higher education. Upon request, you must be able to obtain certified copies of your documentation.
Please use the harmonized Application Form before the deadline of 15-February 2025. Candidates are encouraged to apply early. Applications will be accepted until this deadline and considered on a rolling basis until the position is filled.
Applications submitted by post or email will not be considered. Upon request, you must be able to obtain certified copies of your documentation.
In the evaluation of which candidate is best qualified, emphasis will be placed on education, experience, and personal and interpersonal qualities.

Additional comments

Founded in 1614, the University of Groningen enjoys an international reputation as a dynamic and innovative institution of higher education offering high-quality teaching and research. Flexible study programs and academic career opportunities in a wide variety of disciplines encourage the students and researchers alike to develop their own individual talents. As one of the best research universities in Europe, the University of Groningen has joined forces with other top universities and networks worldwide to become a truly global centre of knowledge.
We offer you in accordance with the Collective Labour Agreement for Dutch Universities: A salary of € 2,770 gross per month in the first year up to a maximum of € 3,539 gross per month in the fourth and final year, based on a full-time position (1.0 fte). In addition, there is an 8% holiday allowance and a 8.3% end-of-the-year bonus. The position is limited to a period of 4 years. The first year constitutes a probationary period, with an evaluation of the candidate's performance after 9 months. The objective of this evaluation is to establish whether the candidate will be able to finish a PhD thesis in the remaining three years. If the performance evaluation is positive, the candidate's contract will be extended by another 3 years, for a total of 4 years.