The Dewson Lab’s research is focused on the powerhouses of cells, structures called mitochondria. Maintaining the integrity and function of mitochondria is essential for cells to survive and to grow. Mitochondria are also central to the process of cell death termed apoptosis.
Defective function and integrity of mitochondria can lead to many diseases including Parkinson’s disease and cancer. Our research uses innovative approaches to better understand how cells in our body maintain their mitochondria to promote cell survival. This information is informing the development of new ways to treat a broad range of diseases with a specific focus of our research on Parkinson’s disease.
Our mission
To undertake cutting edge, imaginative and collaborative research to define the molecular basis of disease. Ultimately, we aim to exploit this fundamental insight to develop new targeted therapies to treat disease of defective cell death, specifically Parkinson’s disease and neuroblastoma.
Impact
Our research has provided new insight into the fundamental cell processes of apoptosis and mitophagy and their role in disease.
Key discoveries include:
We have made key discoveries in the control of PINK1/Parkin mediated mitophagy (Bernardini et al 2018 EMBO J, Gan et al Nature 2022).
Characterised how Bak and Bax function during apoptosis that is now the accepted model of apoptotic pore formation (Dewson et al Molecular Cell 2008, Dewson et al CD&D 2012, Dewson et al Molecular Cell 2009, Ma..Dewson JBC 2013)
In collaboration with the Czabotar lab at WEHI provided the first crystal structures of Bax:BH3-only protein and Bax and Bak homodimers (Czabotar et al Cell 2013, Brouwer et al Molecular Cell, 2014 and 2017)
Identified novel aspects of apoptosis regulation and avenues for therapeutic intervention (Chin et al Nature Comms 2018; Ma et al CD&D 2014; Van Delft et al Nature Chem Biol 2019).
Highlights
Above: Lab photo outside the Parkinson’s Disease Research Centre
Lab research projects
Parkinson’s disease movement symptoms are caused by the progressive death of dopamine-producing neurons. However, how and why these particular neurons die in Parkinson’s is unclear. Our research aims to answer these questions to enable targeted cell death inhibition as an avenue for drugs that can stop or slow neurodegeneration.
Dopaminergic neurons in a dish. Credit: Marlene Schmidt.
People: Marlene Schmidt (PhD), Alex Yeung (PhD), Kaiming Li (PhD).
Collaborators: Guillaume Lessene, Mark van Delft.
My lab utilises novel cell biology and biochemical approaches to interrogate how apoptosis is controlled so that we might better target the process to treat disease. We have identified several novel putative regulators of apoptosis. This project will characterise the role of these proteins in regulating cell death and also investigate their potential role in cancer development.
The project will involve diverse approaches including cell culture, mutagenesis, protein chemistry, mass spectrometry and high-resolution microscopy.
Neuroblastoma is the most common childhood cancer. Whilst in some children the cancer spontaneously resolves, other children have very poor prognosis and respond poorly to aggressive chemotherapy. Our research aims to characterise the putative tumour suppressor function of the E3 ubiquitin ligase Parkin in poor prognosis neuroblastoma. We also aim to identify new therapeutic targets to treat neuroblastoma through genetic screening.
Supported by Worldwide Cancer Research.
People: Ziyan Liu (PhD), Shuai Huang (Postdoc), Iris Tan (Postdoc)
Parkinson’s disease is a highly complex neurodegenerative condition. We need to understand this complexity to take a precision-medicine approach to treat the disease. In collaboration with leading Movement Disorders clinicians at The Royal Melbourne Hospital, we are using cutting-edge and complementary approaches to characterise cells derived from people with Parkinson’s (dopaminergic neurons, astrocytes) to determine their vulnerabilities.
People: Alex Yeung (PhD), Marlene Schmidt (PhD), Shashank Masaldan (Postdoc), Iris Tan (Postdoc), Tahnee Saunders (Postdoc), Dr Andrew Evans (RMH)
Current Parkinson’s models do not fully reflect the chronic and heterogeneous nature of the disease. We are using cutting edge approaches to develop models that replicate the genetic defects in people with Parkinson’s to provide better tools for drug discovery.
Reactive human astrocytes. Credit: Marlene Schmidt
Defective mitochondrial quality control is known to drive inflammation, cell death and is linked to Parkinson’s disease. In collaboraton with the Lazarou lab (Ubiquitin Signalling division, WEHI), we are investigating the mechanisms by which cells (including Parkinson’s patient cells) respond to mitochondrial damage and stress.
People: Tahnee Saunders (Postdoc)
We are exploring the role of ubiquitin enzymes (ligases and deubiquitinases) in the control of cell survival, function and inflammation. These enzymes may represent novel therapeutic targets to either limit cell death in degenerative disease or promote cell death in cancer treatment.
Each member of the lab has their own research focus within the broader context of understanding the fundamental processes of cell death and mitochondrial quality control (mitophagy) and how these processes influence diseases including Parkinson’s disease.
We collaborate widely within WEHI and with external labs. Research positions are available for those with a passion for discovery and translational research.