research
Research Interests
I am interested in the brain, how it works, and how it is affected by disease. More specifically, I am interested in the genetic mechanisms that underlie its function: the changes in gene expression and non-coding RNA. Through understanding these fundamental mechanisms, we can begin to evaluate the changes observed in disease and develop therapeutics to help prevent and reduce the impact of these diseases.
Main Focus of previous Research
I was a Research Fellow at the School of Life Sciences, University of Sussex, Brighton, United Kingdom. My project was to identify ncRNA-based biomarkers in the serum of MND patients.
Amyotrophic lateral sclerosis or motor neuron disease (ALS/MND) is a neurodegenerative disease that affects the motor neurons, causing them to die resulting in muscle death that causes paralysis. In the UK, there is a lifetime risk of 1 in 300, and patients have an average life expectancy of three years following diagnosis, with there currently being no cure for the disease. While about 10% of cases have clear genetic causes, most cases are sporadic with no clear underlying cause. As such, diagnosis of the disease and determining the prognosis is difficult. As such, biological markers of the disease, or biomarkers, are increasingly needed to help with this.
We sought to identify such biomarkers in the serum of MND patients to see whether we can use them to help aid diagnosis, predict prognosis, and track disease progression. We were particularly interested in a class of molecules called non-coding RNA (ncRNA) which are relatively stable in blood and have been shown previously to be useful indicators of diseases such as cancer. Our early results suggest that there are changes in ncRNA in patients compared to healthy people and that we could use to identify people with MND. More recently, it was expanded to look at how these ncRNA change across time with disease progression and to seek those that not only change to help us have objective markers for disease progression, but those that don't change that predict disease prognosis.
This work was undertaken at the University of Sussex with grants funded by the Motor Neurone Disease Association and My Name'5 Doddie Foundation.
Previous Research
My PhD was conducted at the University of Otago, Dunedin, New Zealand to investigate the potential role of microRNA following the induction of long-term potentiation, a continuation of a year-long honours research project. Dynamic regulation of both the mature and primary transcripts of miR-132-3p and miR-34a-5p were found following the induction of LTP in an in vivo rat model, and were found to regulate the crucial gene Mapk1. Computational and molecular biology techniques were used to measure and identify the potential roles of these miRNA in the persistence of LTP.
This project involved a two-month visiting studentship to learn and undertake luciferase assays at the Queensland Brain Institute, Brisbane, Australia under the supervision of Professor Charles Claudianos.
This PhD was undertaken with the supervision of Associate Professor Joanna Williams in the Department of Anatomy, University of Otago, Dunedin, New Zealand. It was done in collaboration with Professor Cristin Print (University of Auckland), Professor Charles Claudianos (Queensland Brain Institute/Monash University), and Professor Cliff Abraham (University of Otago).
Technical Expertise
Bacterial culture, plasmid construction, cloning, and transfection
Bioinformatics
Cell culture
ELISA
Graphic design: Photoshop and Illustrator
Luciferase assays
MiRNA target analysis
Molecular biology
RNA extraction
RNA-seq (Illumina, Nanopore; low amount, small RNA)
RT-qPCR
Western blots