Mapping the proteome vulnerable to unfolding and aggregation under proteostasis stress

Research Opportunity
PhD, Masters by Research, Honours
Number of Honour Places Available
1
Department
Biochemistry and Molecular Biology
Location
Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
A/Prof Danny Hatters dhatters@unimelb.edu.au 83442530 Personal web page
Co-supervisor Email Number Webpage
Prof Gavin Reid Personal web page

Project Details

A healthy state of protein homeostasis (proteostasis) requires balance in the cellular mechanisms that control the synthesis, folding, clearance and transport processes of proteins. In the major neurodegenerative diseases, including Motor Neuron, Huntington, Parkinson, and Alzheimer, these systems become defective providing a heightened probability for unresolved clearance of misfolded proteins, which aggregate, mislocalise and more broadly disturb the physiology of cells. A major gap in our knowledge is a systematic understanding of how the proteome becomes compromised in foldedness or aggregation state as disease manifests.

The aims of this project include determining which proteins in the proteome are particularly susceptible to misfolding and aggregation under proteostasis challenge. Defining these proteins offers rich potential for new therapeutic targets since they would be prime candidates as causative agents in the molecular cascade of dysfunction. In addition, the project will determine whether the proteomes susceptible to misfolding and aggregation are inherently metastable to all stress or are selectively altered by distinct challenges to proteostasis. Third the goal is to determine how proteomes behave in different cell types under stress. This is important to determine because there is evidence that neurons are selectively vulnerable to degeneration under conditions of proteostasis imbalance caused by misfolded proteome accumulation.

This project will use state of the art quantitative proteomics and neuron cell culture models.  The project will also employ CRISPR-Cas9 gene editing technologies.



Faculty Research Themes

Neuroscience

School Research Themes

Biomedical Neuroscience, Molecular Mechanisms of Disease



Research Opportunities

PhD, Masters by Research, Honours
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Biochemistry and Molecular Biology

Research Group / Unit / Centre

Hatters laboratory: Protein misfolding and proteostasis in neurodegenerative diseases

Research Node

Bio21 Molecular Science and Biotechnology Institute

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