Project - Investigating how monocytes directly or indirectly contribute to PD related alpha-synuclein pathology and neurodegeneration

Disease area:

PD

Research Project Objectives:

To determine how direct and indirect monocyte/CNS cell co-culture effects the development of alpha-synuclein pathology; to investigate biological pathway changes the occur following neuro-immune cell interactions and in turn investigate how PD genes involved in innate immunity effect the development of alpha-synuclein pathology. This project is expected to take 3 years (2020-2023)

Research Project Description

Background

PD is a common neurodegenerative condition, with 30 new cases diagnosed per day in Australia alone. There are currently no treatments to stop or slow disease progression as molecular mechanisms underlying PD development are poorly understood. The immune response in PD likely plays a role in the formation of alpha-synuclein pathology and neurodegeneration of neurons, specifically dopaminergic neurons. Although how monocytes, the main effector of the innate immune system, modulate disease progression is still largely unknown. This is in part due to the lack of human cell models.

Aims and Methodology

This project aims to gain a better understanding of how monocytes may affect pathology seen in PD neurons. I propose to utilise human induced pluripotent stem cells (iPSC) obtained from PD patients and differentiate them into neurons, astrocytes and monocytes. I will then be able to culture these cell types together and determine biological changes in the respective cell types through RNA sequencing. This will provide a better understanding of how neuro-immune interactions may contribute to PD, and in turn suggest potential new therapeutic ideas.