Hatters Group

“We investigate novel methods and approaches to study the aggregation behaviour of proteins which are the hallmark of neurodegenerative diseases such as Huntington’s, Alzheimer’s and Motor Neuron Disease (MND). The hope is that we can identify some therapeutic targets” – Danny Hatters

Research

Protein homeostasis and neurodegeneration

The breakdown of protein folding homeostasis (proteostasis) leads to proteome instability and aggregation, which is the most central pathological feature of major neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s and Motor Neuron Disease. Two great challenges exist in this research field. One is in understanding the fundamental efficiency of proteostasis and how dysfunction leads to proteome instability. The other is what the mechanisms are of proteotoxicity caused by mutant proteins that profoundly aggregate, such as mutant Huntingtin, which causes Huntington’s disease. 

Our lab has built a suite of methods and biosensors that enable new capacity to gathering knowledge to the effectiveness of proteostasis, and in separating cells apart that contain mutant proteins in different aggregation states. Our vision is in using this suite to decipher the fundamental mechanisms of proteostasis breakdown in disease and the mechanisms of proteotoxicity arising from these aggregating proteins.  

Specific research questions include

  1. Determining why misfolded proteins, including those associated with neurodegenerative disease, are toxic to cells
  2. How are misfolded proteins recognized and cleared by quality control machinery
  3. What are the mechanisms that give rise to inappropriate protein aggregation in cells
  4. What is the impact of inappropriate protein aggregation on cellular health and homeostasis

Techniques

We are at heart a cell biology and protein biochemistry lab that strives to answer fundamental questions pertaining the interactions of proteins with the surrounding cellular environment in situIn situ refers most commonly to cultured mammalian cell models, but we also occasionally investigate these features in organismal models of disease.  Our research more generally is multidisciplinary involving national and international collaborators in fields of proteomics, chemistry, stem cells, mathematics, bioinformatics, next generation RNA sequencing and modeling.

We also build new methods in chemical biology, proteomics, biosensors and flow cytometry to address our questions.

Group Members

Research Assistant

Angelique Ormsby

Postdoctoral Scientist

Dezerae Cox

Masters Students

Ruo Hua (Helen) Lyu

Graduate Students

Viacheslav Kriachkov

Poly Talukdar

Yoon Hee Choi

Farheen Farzana 

Visiting Intern student

Wenquan Zhao

Biography

Danny Hatters is an NHMRC Senior Research Fellow (2019-2023) and runs a research laboratory to study how proteins misfold and interfere with cellular functions, with a particular focus on mechanisms related to neurodegenerative disease.  The research combines building new tools, biosensors and methods using various aspects of protein biochemistry and cell biology.  He completed his PhD at the University of Melbourne in 2002 studying the biophysics of amyloid formation.  He then completed his post doc at the Gladstone Institutes/University of California, San Francisco under the mentorship of Dr Karl Weisgraber from 2002-2007 studying the structure and function of apolipoprotein E4 protein, which is an important modifier of Alzheimer’s disease risk.  In 2007, he returned to Melbourne to take up a CR Roper Fellowship position in the Department of Biochemistry and Molecular Biology to establish his own (current) research program. In 2012 he was awarded an ARC Future Fellowship and appointed faculty member of the Dept of Biochemistry and Molecular Biology.  He was deputy head of department from 2017-2019.