Midbrain organoids as Parkinson’s disease models

Accurate models are needed for studying the human brain and the diseases affecting it. This project aims to create an immunocompetent organoid model of the human midbrain and explore possible downstream applications, such as organoid-on-chip, transplantation and humanized models.

LRRK2-mutation and glial cells in Parkinson’s disease

This project aims to discover the effects of LRRK2 G2019S-mutation on microglia and astrocytes, and glial interactions impact on neuronal well-being. LRKK2 G2019S –mutation is one of the most common causative mutation in Parkinson’s disease.

Blood-brain barrier on a chip for disease modelling and drug testing

Blood-brain barrier (BBB) is a semipermeable membrane that separates the central nervous system from the periphery. This project aims to develop an in vitro model of BBB by using human iPSC-derived ECs, pericytes, and astrocytes in a microfluidic organ-on-chip (OOC) platform. Using human cells avoids the problems related to cross-species differences, while the OOC platform provides a more in vivo-like environment. The model will be utilized in disease modeling and used to study the role of BBB in PD pathology by using iPSCs from PD patients.

Early Lewy body inclusions and genetic screening

Lewy bodies are present in multiple neurogenerative diseases, such as Parkinson’s disease, Alzheimers disease and Lewy body dementia. α-synuclein is one of the key molecules found inside of Lewy bodies and it is routinely used to model α-synuclein pathology and Lewy body-like inclusions in neurodegenerative disease models. We hope to establish in vitro model with more authentic Lewy bodies using multiple molecule approachment.

Pericytes in Parkinson’s disease

Pericytes are perivascular cells surrounding the vasculature all around the body. In the central nervous system, they maintain the function of blood-brain barrier (BBB), regulate inflammation, and take up and degrade different proteins. This project aims to find out how the LRRK2 mutation alters pericytes function and how these changes relate to BBB disruption and neuroinflammation in PD.

Microglia in α-synucleinopathies

Microglia are responsible for the inflammatory response as well as clearing away accumulated debris in the brain. Recent data has indicated that microglia may contribute to disease by producing an overactive proinflammatory response and having a dysfunction in their ability to phagocytose pathological proteins, including α-synuclein. This project aims to shed light on this process through disease modelling and identify possible therapeutic targets.

Microbiota-gut-brain-axis in Parkinson’s disease

Dysfunction of the enteric nervous system as well as an altered gut microbiome have been suggested to play a crucial role in Parkinson’s disease pathology. This project aims to unveil the role of gut changes in Parkinson’s disease and identify potential therapeutic targets by creating in vitro models of the microbiota-gut-brain-axis. The project will utilize human iPSC-derived enteric and dopaminergic neurons together with cells forming the gut and blood-brain barriers, on a microfluidic device.