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Characterisation of the Kir4.2 channel as a critical new target for Parkinson’s disease

 

  • Principal Investigator: Dr. Linlin Ma, Griffith University
  • Co-Principal Investigators: Dr. Ernst Wolvetang, The University of Queensland

 

Project Summary:

 

Linlin Ma and her collaborators have identified a mutation in the KCNJ15 gene that is present in multiple generations of an Australian family with Parkinson’s but is not present in a large cohort of healthy controls. KCNJ15 knockout mice created by another group many years ago showed some motor phenotypes, but unfortunately this mouse line was not preserved. Preliminary data shows that the KCNJ15 mutation from the Australian family is a loss-of-function mutation. With this funding, the Ma group will continue to create iPSC lines from this family, along with gene-corrected controls. They will convert these iPSCs into dopaminergic neurons in vitro in order to assess what effect this mutation has on neurons. In parallel, they will also characterize a KCNJ15 knockout mouse model for motor phenotypes, pathology, and inflammation. KCNJ15 belongs to a group of biological targets that are very druggable, so successful results from this project could suggest a new target for Parkinson’s, along with readily available tools to develop and test therapeutics.

 

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About Dr Linlin Ma

 
I am a molecular biologist and physiologist in the ion channel research field. Ion channels are a group of pore-forming membrane proteins that facilitate and control the diffusion of ions across biological membranes. They underlie a wide variety of biological processes, varying from neurological excitability to T-cell activation and insulin secretion. Accordingly, the malfunction of different ion channels could lead to a variety of diseases such as epilepsy, cystic fibrosis, pain, etc.
 
My major research interest is to understand the gating properties and functional features of interested ion channels in related pathological settings. Using methods in molecular biology, electrophysiology (patch clamp), cell biology and protein biochemistry, my lab mainly focuses on elucidating the pathological roles of potassium channels and calcium channels in neurological diseases, such as Parkinson’s disease, and identifying new channel modifiers from natural resources.