Fighting against Parkinson's disease: the pathway paved by ion channels

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1. SUMMARY

We see, we hear, we feel. We memorise, we think, we innovate. All the sensations and movements in every scenario of our life are regulated by a group of complex molecules called ion channels. These molecules are proteins that transport ions, such as sodium, calcium, potassium, across the otherwise impermeable cell membranes in a highly regulated manner in each cell of our body. They control the generation and propagation of neuronal pulses, secretion of hormones, regulation of cell volume and many more. Accordingly, malfunction of various ion channels causes all kinds of diseases, varying from diabetes to hypertension, pain, muscular dystrophy and many others. My research focuses on understanding how some of the ion channel members, such as TRP channels and voltage-gated potassium channels, are involved in the mechanism of diseases such as Parkinson’s disease, and how to overcome these diseases using potential new drugs derived from nature.

2. BENEFIT

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease, with a prevalence of approximately 0.5-1% among those 65-69 years of age, rising to 1-3% among persons 80 years of age and older. In Australia, more than 13,500 new cases are diagnosed every year and 15% of PD patients are working age. Due to the debilitating symptoms of PD and related complications, the total economic cost of PD in Australia was over $9.9 billion in 2014 and estimated at over $12.3 billion in 2018. Currently, 18,500 Queenslanders are living with this devastating disease. Unfortunately, there is still no effective therapeutics available yet.


The difficulty of treating PD is multifaceted. Lack of definitive diagnosis at the early stages and challenges in the management of symptoms at later stages are certainly key issues to address. However, the evolving layers of complexity in the pathogenesis of PD has become the most critical hurdle for us to conquer this disease. It is therefore urgent to unravel new biological targets critical for pathogenesis of the disease, aiming for novel therapies to slow down or reverse the disease progression.


In this research, I work with Queensland Parkinson’s Project (QPP), which has collected samples and information from over 4000 participants, 50% of being PD patients. Among the patients, 28% had reported family history of Parkinsonism. By genetics studies, several novel genes that are associated with PD have been identified, including ion channel encoding genes. Working with a team at Griffith Institute for Drug Discovery (GRIDD), I aim to elucidate how the related ion channel proteins contribute to PD and identify novel drug leads to modulate the channel functions from natural sources. To do this I am using a unique Queensland resource called NatureBank library hosted by GRIDD at Griffith University. NatureBank is a unique drug discovery platform based on natural product extracts and fractions derived from Australian plants, fungi and marine invertebrates. Currently, 20,000 natural product extracts and 30,000 archived biota samples are available for high-throughput screening.


In this project I am also using a unique Queensland cell bank of human induced pluripotent stem cells collected from PD patients and controls. These cells will be further differentiated into neural cell types to be used as research models in this study. From this project, we aim to benefit Queensland in three folds. First, resources unique to the Queensland Parkinson’s Project will be further developed and enriched. This unique platform built in Queensland has already contributed to the universal PD data library and will attract more collaborations internationally in the future. Second, outcomes from this study will not only shed new light on our understanding of the mechanism of PD, but also help the PD patients involved in QPP understand their disease better and provide guidance for their family members. Lastly, using Australian natural product derived compounds for new channel modulator discovery will highlight the unique value of Australia originated natural products and attract more interests from industry and academics in the field of drug discovery.

3. ENGAGEMENT

Diseases and related medical science are mysterious for many patients and the general community. I believe that scientists have the responsibility to introduce their scientific research in an easily understandable way to the general public, even though it would be a hard task in most cases due to the complexity of the research. To practice this belief, I participate scientific forums for general audiences. The most memorable one is when I was invited for the first time to give a talk about my research on myotonia to a group of myotonia patients and their families. I explained what we have done to alleviate the symptoms using plain language. The sparkles in the eyes of the audience, the smiles on their faces and the laughter in the room gave me confidence that they understood, which greatly encouraged me. I then extended this positive experience wherever possible, even in my child’s school excursions.


Being a lecturer, I am very lucky to have many opportunities to nurture interest in STEM in my classrooms and lab. I volunteered to be an ambassador when high school students came to visit us. I invited them to attend our lab meetings, have lab tours, work on small projects and communicated with them about what it is like to be a scientist. For various reasons, more than half of the students who enrolled in science programs in a university will not become a scientist after graduation. To promote the students’ passion in science, I try my best to make my classes interesting and encouraging, and often add multidisciplinary content and examples in my lectures and tutorials. I actively encourage my undergraduate students to gain some science project experience and have trained them myself in the lab. On a “Thank you” card that my project students prepared for me when they finished their projects, they said my passion in science and education significantly inspired them and they will pursue their career in STEM like me. That was the most exciting card I have ever received! An Honours student I supervised told me that, before she started her Honours degree, her career plan was to become a lab technician or sales representative after graduation. But she graduated with a first class Honours and a Chancellor’s award, and she enjoyed her experience so much that she decided to continue with a PhD instead and become a scientist. No reward is better than this for a teacher.


The future of STEM in Australia relies on our young blood. Only when these next generation of decision makers have real interest and passion in STEM, could they be motivated to innovate and change the world. This is the ultimate mission of every STEM educator. I deeply enjoy nurturing next generation scientists and look forward to making this happen even earlier, in high school, primary school or kindergarten.

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