Doctoral Candidate Position 3 - University of Groningen the Netherlands
Activation and function of LRRK2 in macrophages
Simone Attisani obtained his Bachelor's degree in Biological Sciences from the University of Ferrara in 2021 and his Master's degree in Biology from the University of Milano-Bicocca in 2024. From January 2023 to March 2024, he completed an internship at the Italian Institute for Genomic Medicine (IIGM) in Turin, where he conducted his Master's thesis on the epigenetic regulation of CD8+ T lymphocytes in chronic immune responses. In May 2025, Simone began his doctoral studies within the BICEPS MSCA Doctoral Network, focusing on the role of the immune system in Parkinson's disease. Under the supervision of Prof. Dr. Arjan Kortholt in the Cell Biochemistry Unit, his research aims to elucidate the role and behaviour of LRRK2 in immune cells. His current work investigates LRRK2’s response to specific cellular stress conditions, while his forthcoming project, beginning in January 2026, will examine the effects of Parkinson's disease-associated environmental factors on LRRK2’s behaviour in macrophages.
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.