In 2013, I co-led the creation of the Centre for Motor Neuron Disease Research at Macquarie University.  This Research Centre takes a multidisciplinary approach to unravelling the molecular origins of MND through identifying the genetic and epigenetic causes of MND, biochemical and proteomic evaluation of protein defects in MND, cell biology and animal models of disease, and patient biomarker studies and clinical trials. My current research program involves a multidisciplinary approach including proteomics, molecular and cellular biology, synthetic biology and molecular bioengineering, neuropathology and neuroimaging, and animal models of MND/neurodegeneration. I work closely with valued collaborators Dr Albert Lee and A/Professor Marco Morsch. Several of my current research projects are described briefly below:

Understanding the role of abnormal protein aggregates in MND disease mechanisms | This program of research aims to understand how mutations in MND proteins cause them to inappropriately aggregate and accumulate inside motor neurons, and how this leads to degeneration. Our studies have focused upon characterizing a new MND gene (CCNF) we have identified in a project led by Professor Ian Blair and A/Professor Kelly Williams (Williams et al, Nature Communications, 2016). Our research has now mapped out in precise detail how the resultant mutant cyclin F protein causes specific defects in the ubiquitin-proteasome system, ultimately leading to inappropriate accumulation of proteins that causes apoptosis (Lee et al, 2017; 2018; Hogan et al, 2017). A key discovery was the identification of TDP-43 as a specific ubiquitylation substrate of cyclin F (Rayner et al, 2022), and the corresponding demonstration that cyclin F is an endogenous regulator of TDP-43 homeostasis. 

Developing AAV gene therapies for MND | We have determined that therapeutic overexpression of cyclin F can clear pathological accumulation of TDP-43 in experimental models of MND. Through this process, we have bioengineered therapeutically-optimised variants of cyclin F. We have also used some innovative synthetic biology approaches to create molecular switches that can be used to control the levels of therapeutic gene expression. We are currently undertaking pre-clinical trials of the cyclin F AAV-gene therapy – supported through a FightMND Drug Development Grant.

In December 2022, I co-founded Celosia Therapeutics, a Macquarie University launched spin-out company that seeks to develop multiple gene therapy assets.

We are always on the look out for enthusiastic researchers to join our program. At the moment, we are particularly interested in people with skills in molecular biology, synthetic biology, and computational biology/bioinformatics/AI (particularly non-coding RNA, and RNA-protein interactions).