Laura Hughes

After completing a Bachelor of Biomedical Sciences with First Class Honours degree at the University of Otago in New Zealand, Laura secured a Research Assistant position at the University of Sydney’s Brain and Mind Centre. After two years of working, Laura decided to pursue PhD study in the same laboratory group with an exciting project focused on peripheral blood biomarkers for Parkinson’s Disease, and is nearing the end of her first year.

Forefront Group: Halliday Lab

Supervisors

Dr. Nicolas Dzamko, Prof. Glenda Halliday

Affiliate Organisations

Brain and Mind Centre, University of Sydney

Expertise:

  • ONeurodegeneration
  • Biomarkers
  • Immunology
  • Cell Biology

Neurodegeneration of interest:

Parkinson's disease, Idiopathic REM behaviour disorder (iRBD)

Specific Skills:

  • Cell culture
  • Flow cytometry
  • Western blotting
  • ELISA

Project - Evaluating Peripheral LRRK2 and GCase as Biomarkers for Parkinson’s Disease

Disease area:

Parkinson's disease

Research Project Aims

  • 1. Assess LRRK2 and GCase enzyme activity, lysosome function, and inflammatory responses in induced pluripotent stem cell (iPSC)-derived monocytes from GBA1 (GCase-encoding gene) mutation carriers.
  • 2. Measure LRRK2 and GCase enzyme activity and lysosome function in peripheral blood immune cells from LRRK2 and GBA1 mutation carriers.
  • 3. Assess the response to pathogen challenge in peripheral blood immune cells from LRRK2 and GBA1 mutation carriers.
  • 4. Assess LRRK2 and GCase enzyme activity and lysosome function in monocytes from iRBD patients.
  • 5. Determine the effect of toll-like receptor stimulation on monocyte GCase activity.
  • 6. Evaluate the effect of small molecule GCase activators on monocyte GCase activity.

Research Project Description

Background:

Parkinson’s disease (PD) is a chronic, progressively debilitating neurodegenerative disease with no available cure or disease-modifying treatment at present, which can be largely attributed to the lack of biomarkers to enable early detection, diagnosis, prognosis, and stratification of PD. Leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase), two PD-associated proteins highly expressed in peripheral blood cells, have been identified as potential biomarkers and therapeutic targets for PD, and will be the primary focus of my project.

Objectives & Methods:

Outcomes from the above objectives will provide new information on the interaction between LRRK2 and GCase activities in peripheral blood cells and uncover how PD-associated mutations in these genes alter their activities. Results from this study will reveal any differences in LRRK2 and GCase enzymatic activity, inflammation, and lysosome function between the different cohorts (LRRK2/GBA mutation PD patients, non-manifesting mutation carriers, and idiopathic PD patients). Outcomes from objective 4 may identify peripheral blood biomarkers indicative of iRBD conversion to synucleinopathic disease, which would enable early therapeutic intervention in these patients.

Experiments will predominantly utilise flow cytometry to measure LRRK2 and GCase enzyme activity in primary blood cells obtained from patients. Other methods to be used include western blotting to determine protein levels, and cytokine ELISA assays to examine inflammatory responses.

Thank you for your interest in my project!