Team Kirik

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PD Functional Genomics | 2020

In Vivo Approach to Elucidate the Pathobiology of Parkinson’s-associated Genes Using Human Diseased Neurons

Study Rationale: Several genes are known to be associated with Parkinson’s disease, although how they impact the disease process is not fully understood. Team Kirik will use stem cells from patients in whom the genetic cause is known and perform mechanistic studies to elucidate the interactions between three key genes and how they impact the function of cells in the brain.

Hypothesis: This project will provide new insights into the role specific gene mutations play in the development of disease features in cell types known to be affected in Parkinson’s disease.

Study Design: Stem cells generated from patients with neurological disease, including Parkinson’s disease, provide a tool for researchers to study and understand mechanisms underlying the disease. One limitation of this approach is that the cells are maintained in culture dishes in the laboratory in an artificial environment that does not closely model that of the disease. This project proposes a unique approach involving the transplantation of the human cells into mice in order to study them in the living brain and thus reveal new insights into disease mechanisms.

Impact on Diagnosis/Treatment of Parkinson’s Disease: Researchers’ ability to design better treatments for Parkinson’s is directly related to the level of understanding on the basic biological processes governing the initiation of the disease process and how the disease progresses from that point onward. This information is critical in efforts to intervene with the disease process.

Leadership
Deniz Kirik, MD, PhD
COORDINATING LEAD PI

Deniz Kirik, MD, PhD

University of Sydney
Clare Parish, PhD
CO-INVESTIGATOR

Clare Parish, PhD

University of Melbourne
Jennifer Johnston, PhD
CO-INVESTIGATOR

Jennifer Johnston, PhD

NysnoBio, LLC
Lachlan Thompson, PhD
CO-INVESTIGATOR

Lachlan Thompson, PhD

University of Melbourne
Courtney Wright, PhD
Project Manager

Courtney Wright, PhD

University of Sydney
Glenda Halliday, PhD
Co-Investigator

Glenda Halliday, PhD

University of Sydney

Project Outcomes

This project will use patient-derived cells from genetic forms of PD, studied in the environment of the living brain, as a unique paradigm to reveal cellular components of PD pathobiology. View Team Outcomes.

Team Outputs

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Overall Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of November 2023. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific theme.

Impact

Theme

Featured Output

Below is an example of a research output from the team that contributes to the ASAP mission of accelerating discoveries for PD.

Generation of human-induced pluripotent-stem-cell-derived cortical neurons for high-throughput imaging of neurite morphology and neuron maturation

Robust, high throughput cell imaging-based assays required well-optimized cell culture conditions to effectively image and analyze cells. Team Kirik has developed a protocol to generate mature brain cells, specifically cortical neurons, that are ideal for automated microscopy imaging and analysis. Utilization of these cell lines in combination with high-throughput imaging, allows for the rapid analysis of highly-detailed cortical neuron images.

Team Accolades

Members of the team have been recognized for their contributions.

Other Team Activities

  • Working Group: iPSC – Clare Parish (Co-Chair)
  • Interest Groups: iPSC Models (Neurons/Glia/2D/3D) – Clare Parish (Chair)

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