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Personal profile

Research interests

Our Laboratory studies the structure and function of proteins involved in the fibrinolytic system, memory and neuroplasticity and innate immunity; specifically their roles in human health and diseases.

 

Biography

I did my PhD and my first postdoc in the field of yeast mitochondrial bioenergetics under the supervision of Profs Philip Nagley and Rodney Devenish at Monash University. I then worked on translational research using recombinant proteins for diagnostic applications. In Autogen, a biotech company directed by Prof Ian Mackey and Prof Merrill Rowley at Monash, we studied autoantibodies in Type II diabetes mellitus patients using recombinant glutamic acid decarboxylase (GAD) I developed. In the Molecular Parasitology group led by Prof Terry Spithill, my work on a protease called cathepsin B from liver fluke was later developed into a diagnostic kit for fluke infection. In 2002, I joined the Structural Biology Group led by Prof James Whisstock where I became a structural biologist with a focus on structure and function relationships of complex proteins. I have gained extensive experience in developing, producing, purifying and characterizing human proteins for structural studies. As such, I have solved the first X-ray crystal structures of human full-length plasminogen, alpha2-antiplasmin, GAD and perforin and many others.

In 2017, I was appointed a research group leader in the Molecular Biology Department with a key focus to understand the intermolecular interaction between molecules (e.g. plasminogen and perforin) and their functional partners as well as their translational applications. I use techniques such as x-ray crystallography, small-angle x-ray scattering, fluorescence microscopy and cryo-electron microscopy. I enjoy being a hands-on researcher tackling challenging targets and mentoring students in developing their careers within and outside research.

My current research interests include:

Regulation of fibrinolytic proteases. My key interest is the structure and function studies of plasminogen, plasminogen activators and plasmin inhibitors. I want to gain a better understanding of the regulatory mechanism of plasminogen activation and plasmin inhibition and to utilize such knowledge in the development of therapeutic molecules that can modulate the activation/inhibition process in disease settings. Further, through collaboration with experts in the field, I study the role of plasminogen in wound healing, such as muscle regeneration following injuries.

 

Structural and functional studies of pore forming proteins and complexes. Our studies in this field leads to a better understanding of the biological mechanisms through which mammalian pore forming proteins eliminate infected or transformed cells, pathogens and in immunity. I work alongside a team of perforin biologists, medicinal chemists and single molecule fluorescence microscopists in developing small molecule pore forming perforin inhibitors to combat allogeneic bone marrow transplant rejections on a Wellcome Trust-funded drug discovery project.

 

Structure and function studies of glutamic acid decarboxylase (GAD). Significantly, GAD65 and GAD67 play a key role in the central nervous system where dysfunction of the enzymes leads to an imbalance of the neurotransmitter inhibitor γ-butyric acid (GABA) in the synapses and has implications in the development of neurological disorders such as anxiety disorder, stiff-person syndrome, epilepsy and chronic pain. My current focus is on the impact of GAD autoantibodies on GABAergic neurons and limbic encephalitis and the regulation of GAD function.

 

Developing new strategies to optimize data collection of small and difficult crystals for structural studies.Since 2013, on three separate occasions, I have led a team of scientists from University of Melbourne, La Trobe University, Monash University and Australian Synchrotron to perform experiments using the X-ray Free Electron Laser (XFEL) beam in LCLS, USA. We collected data and ran comparisons on data quality and diffraction limits using both the standard synchrotron and XFEL techniques. I was invited to participate in the 5th Ringberg Workshop on Structural Biology with FELs 2018. Currently my focus is on single molecule in-tray data collection using synchrotron energy.

 

Development of pipelines and infra structures to generate human monoclonal antibodies I am a cofounder of The Monash Human Monoclonal Antibody Library Group; we have generated a Monash University High-diversity Synthetic Human Phage Fab Library to overcome the huddles in developing human therapeutic mAbs, including humanisation of murine mAb or the use of human immunoglobulin transgenic mice. We have designed phage displayed human antibody libraries, where a repertoire of recombinant human antibodies is expressed on bacteriophage particles at a 1:1 ratio, which allows their affinity-based selection and subsequent sequence identification. The phage synthetic libraries provide rapid screening, a wider range of potent clones and are simple and cheap to implement.

 

I am passionate in providing mentorship and training for female migrant scientists, my aim is to help with their transition from overseas to employment in Australia. I provide laboratory training, advise on professional development, job applications and further studies. I have mentored more than six individuals in the past 10 years. I also mentor younger female researchers experiencing career disruption.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research area keywords

  • Structure/Function (Health/Safety/Medical)
  • X-ray Crystallography
  • Small Angle X-ray Scattering
  • Electron Microscopy
  • Immunology

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