Doctoral Candidate Position 11 - H. Lundbeck A/S & University of Aarhus, Denmark
Qualification and rank-ordering of microglia/macrophage targeting principles for potential treatment of Parkinson's Disease
Ling earned her bachelor's degree in Applied Biological Chemistry from Tohoku University in
2022. During her undergraduate studies, she conducted research under Prof. Masako Toda,
investigating the induction of innate immune memory by food-derived compounds in primary
immune cells and examining their anti-allergic potential in mice.
She then pursued a master's degree in Medical Sciences at The University of Tokyo,
specializing in neuroscience, and completed it in 2024. Continuing as a research assistant in
the same laboratory, she worked with Prof. Shigeo Okabe to study the nuclear morphology of
microglia in the developing somatosensory cortex of mice. Her research experience has
fostered a strong interest in neuro-immune interactions, particularly in understanding how
immune cells influence brain development and function.
In the past, Ling was rewarded the Excellent Poster Award at the 80 th Annual Conference of
the Japanese Society of Microscopy in 2024. She also received the scholarships, including
ITO Foundation Scholarship for International Education Exchange in 2022-2024 and Japan
Monbukagakusho Honors Scholarship for Privately-Financed International Students in 2018-
2019.
Description of project
In the BICEPS collaboration the overall hypothesis is that Parkinson's Disease (PD) must be considered as a systemic disease where both the peripheral and central immune response plays a role in the pathophysiology.
In this project we will correlate activation stages of central microglia and peripheral macrophages at the single cell level in an advanced animal model of seeded alpha-synuclein aggregation to the inflammatory state of activated human iPSC derived microglia and macrophages to develop a set-up for qualifying and prioritising targets for potential treatment of PD.
More specifically the student will (i) Define microglia and macrophage subpopulations and their activation states in a well-established alpha-synuclein seeding model in mice (developing progressive alpha-synuclein pathology and microglia activation) at different stages of disease progression using single-cell RNA sequencing and more functional analysis (fx. cytokine analysis) (ii) Compare the transcriptomic profiles to stimulated human iPSC-derived microglia and macrophages in culture to understand what disease stage we can capture in vitro (iii) Rang-order microglia/macrophage targeting principles (small molecules and antibody tools) in vitro based on correction of gene expression and using functional assays (cytokine release and phagocytosis) (iv) Apply the 1-2 most promising principles targeting microglia and macrophages to the in vivo model to build the correlation between the iPSC culture model and the effect on inflammation in vivo (v) Assess the effect of modulating the inflammatory state of microglia/macrophages on alpha-synuclein pathology development using methods based on new antibody tools.
The student will be part of a Neuroscience Research unit specialised in developing new treatments for diseases in the central nervous system. The fundamental methods in the project; the animal model of seeded aggregation and human iPSC differentiation to macrophages and microglia are well-established in our laboratories. The project will furthermore involve biochemical techniques, RNA scope, novel immunocytochemistry methods to detect alpha-synuclein pathology, advanced microscopy, single cell RNA sequencing and functional analysis of macrophages/microglia.