MND Research Australia has awarded 2022-24 PhD top-up scholarships to four outstanding early career researchers: Jeryn Chang and Jianina Marallag from the University of Queensland, Katherine Lewis from the University of Melbourne and Sean Keating from the Queensland Brain Institute.
Jeryn Chang | University of Queensland
Decoding the loss of appetite and pathophysiology of the brain in motor neuron disease
The loss of appetite is observed in patients with MND. This is clinically important, as energy deficits and weight loss are associated with faster disease progression and earlier death. My studies aim to identify the impact of MND on the hypothalamus, a small area of the brain that regulates appetite, and how this may contribute to functional deficits throughout the brain. Studies aim to provide a biological basis for the loss of appetite in patients with MND, which will enhance understanding of disease, and provide insights to better manage care strategies aimed at improving quality and duration of life.
Sean Keating | Queensland Brain Institute, University of Queensland
TDP-43 and protein clearance in the pathogenesis and treatment of MND
In MND, toxic clumps of proteins accumulate within the brain and spinal cord, leading to neurodegeneration. Using human MND tissue, neurons grown in a dish, and genetically modified MND mice, I aim to investigate how dysfunctional cellular “waste removal” systems cause protein clumping in neurons. I also aim to discover new ways to effectively stimulate these “waste removal” systems with drugs and gene therapies, and determine whether this can increase the break-down of toxic protein clumps and protect against disease. By stopping protein clumping, we aim to extend neuron survival as a therapeutic strategy to treat people living with MND.
Katherine Lewis | University of Melbourne
Characterising Myelin Changes in Motor Neuron Disease
Despite garnering much deserved attention and funding, the primary causes underlying MND onset and progression remain elusive. This, in part, may be due to most MND research being conducted with a neuroncentric focus. We know that motor neurons are encased in a lipid-rich sheath termed myelin, which is essential for neuronal health and survival. We also know that the cells that produce the myelin have been shown to exhibit MND pathology. However, the exact role of myelin-producing cells in MND remains unclear and it is unknown to what degree their dysfunction contributes to MND onset and progression. Thus, this PhD project aims to comprehensively characterise myelin changes in MND over the course of disease, using clinically relevant mouse models, complemented with sophisticated stem cell derived ‘mini brain’ model systems. By understanding the role of myelin in MND, we can provide insight into new treatment avenues and therapeutic targets to preserve motor neuron health and function.
Jianina Marallag | University of Queensland
The potential role of CXCR2 activation in motor neuron disease
Excessive activation of the immune system has been found to result in motor neuron death in MND. CXCR2 is a cellular receptor that is gaining interest for its involvement in recruiting immune cells to the site of injury. Inappropriate activation of this receptor may contribute to the progression of MND. This project will utilise a drug that blocks CXCR2 in mouse models of MND and patient samples to investigate if it is able to protect motor neurons by reducing immune system activity. The results will help determine if CXCR2 can be used as a therapeutic target for MND patients.