The role of VPS35 in transporting proteins that help brain cells communicate
Dr. Chelsia Kadgien | University of British Columbia
$30,000 (2 years) Porridge for Parkinson’s Dr. Robert Lorne Alexander Graduate Student Award
This study examined a protein, VPS35, which facilitates transportation within cells. Genetic mutations can cause VPS35 to malfunction and are associated with Parkinson’s disease. Dr. Kadgien’s study examined how receptors, which received communication signals sent between cells (called neurotransmitters), are transported to their correct location.
Specifically, Dr. Kadgien’s graduate study focused on how the Parkinson’s mutation affects receptor transport. She found the mutation affected receptor transportation in cells and as a result, caused significant changes in how communication signals were sent out and received. Differences were observed in both cell and animal models and suggest the VPS35 mutation disrupts how cells communicate with each other.
Thanks to the funding provided by Porridge for Parkinson’s, Dr. Kadgien attended multiple conferences to present her work and participated in an intensive training course to strengthen her scientific abilities. Additionally, work completed over the course of the funding cycle was submitted for publication.
Note: This brief has been updated to reflect that Chelsia Kadgien achieved a PhD from the University of British Columbia in 2020.
A letter from Chelsie
I am writing today to offer my sincere thanks for the opportunities provided to me through the Porridge for Parkinson’s (Toronto) Dr. Robert Lorne Alexander Graduate Student Award.
This award has enabled me to study the effects of a gene mutation that causes Parkinson’s disease on the structure and function of brain cells in a new mouse model of the disease. Over the last two years, I have discovered that this mutation changes how proteins involved in trafficking neurotransmitter receptors to and from the cell surface bind to one another, and how they accumulate within brain cells. The functional consequence of this is that the level of communication between cells in the brain is changed. This finding is very exciting, as it demonstrates that this mutation causes similar changes in cell to cell communication as have been described in models of other PD genes, showing that different causes of the disease have similar effects. This is particularly important for developing new treatments as it points to a common pathway that could be targeted by new pharmaceuticals. I have recently drafted a manuscript for publication that we will be submitting to the journal eLife this week.
This award has also afforded me excellent opportunities to share my work and collaborate with other Parkinson’s disease researchers. I was recently able to attend the Gordon Research Conferences biennial Parkinson Disease meeting in Maine, where I shared my work with the Parkinson’s research community and was able to establish an exciting collaboration with researchers from l’Université de Montréal.
The award has also enabled me to take a visiting student position at the Montréal Neurological Institute at McGill University, where I will be completing my PhD work. The MNI has an incredible program of Parkinson’s research; here I have access to world leaders in topics highly relevant to my project. Since my arrival at McGill last fall I have had numerous opportunities to present my work and receive feedback from the faculty, as well as receive training in new techniques from other laboratories here.
Your support has meant a great deal and has allowed me to pursue some truly wonderful opportunities. I’d like to offer my heartfelt gratitude for your donation.
2015 Project Summary
At the University of British Columbia, PhD student Chelsie Kadgien is zeroing in on the function of a particular gene that, when mutated, is linked to late-onset Parkinson’s disease. Ms Kadgien investigates VPS35 to see if its role in transporting proteins that help brain cells communicate could eventually become the target for a drug that could disrupt or repair the problems that damaged forms of the gene cause.
L.N. Munsie, A.J. Milnerwood, P. Seibler, D.A. Beccano-Kelly, I. Tatarnikov, J. Khinda, M. Volta, C. Kadgien, L.P. Cao, L. Tapia, C. Klein, M.J. Farrer, Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson’s disease VPS35 mutation p.D620N, Human Molecular Genetics, Volume 24, Issue 6, 15 March 2015, Pages 1691–1703, https://doi.org/10.1093/hmg/ddu582