BIOM03 Discovery and validation of new treatments for Motor Neuron Disease

Overview

Amyotrophic Lateral Sclerosis (ALS), also called Motor Neuron Disease (MND) is a devastating and fatal neurodegenerative disorder for which there are currently no effective treatments to slow or stop disease progression after diagnosis. The prevalence of ALS is increasing rapidly in Australia and this takes an enormous socioeconomic toll on people diagnosed with the disease and their families. Thus there is urgent unmet medical need to discover and validate new treatments for ALS that can slow or prevent loss of motor neurons in the brain and spinal cord, and thereby slow disease progression. Our lab has uncovered multiple neuroprotective agents which are at the early stages of validation as potential new drugs. This project will evaluate, some of these compounds using cultured neurons and immune cells as models of Motor Neuron Disease in a dish.  Specifiallcy, the student projects will involve

1. Evaluation of novel therapeutics to determine if they can reduce neuroinflammation, oxidative stress and protein aggregation in MND models
2. Conducting neuroprotective efficacy of new therapeutic agents to prevent or rescue motor neuron death, inflammation and aggregation triggered by neurotoxic MND proteins (SOD1, TDP43 and C9orf) in patient-derived cell models.
3. Identifying new targets for neuroprotection using samples from previous animal studies and patient samples in our laboratory.

Research engagement

• Literature Review
• Laboratory Experiments involving molecular biology, proteomics, pharmacology, neuroscience techniques based on research interests
• Data Collection
• Data Entry
• Drafting or revising conference papers or journal articles

Research activities

The research will involve working with immune cells, animal tissues from disease models and potentially patient samples to understand the causes of MND and development. The trainee will be able to conduct conduct dose and time kinetic studies to determine the optimal dose and duration for activating immune cells and protecting motor neurons from degeneration using cellular models of the disease. Downstream analyses will include real-time quantitative polymerase chain reaction (qPCR) and western blot techniques will be employed to detect the upregulation of target molecules. Surface molecules will be confirmed using flow cytometry, while the release of inflammatory molecules in the supernatant will be measured through enzyme-linked immunosorbent assay (ELISA).

Outcomes

The outcome of this project will provide insights into the causes and mechanisms of Motor Neuron Disease and uncover new targets.

Skills and experience

Previous lab experience, and in particular, cell culture experience will be beneficial but not required.

Start date

1 November, 2024

End date

21 February, 2025

Location

Translational Research Institute (TRI)

Additional information

Students can start ASAP

The topic is attached to an existing funded project

Contact

Felicity Han