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Student research project 

Supervisor(s): Dr Tin Kyaw and Professor Alex Bobik

People survive an initial heart attack (myocardial infarction-MI) due to recent advancements in intervention. However, these survivors are at higher risk of recurrent, often fatal attacks and currently it is impossible to predict patients who are at highest risk. We are aiming to identify MI-induced IgGs and develop ELISA-based diagnostic tool to identify patients with high-risk.

Project summary

Myocardial infarction (MI) is the leading cause of death in Australia with up to 40% of MI attributed to recurrent attacks. After an initial MI the risk of recurrent attacks increases and remains elevated for many years. Despite intensive use of lipid-lowering drugs, patients who survived a first attack are more likely to suffer from fatal recurrent attacks, increasing mortality rates to 24% at 1 year, 51% at 5 years and 65% at 8 years, indicating undefined cholesterol-independent mechanisms in the MI-aggravated atherosclerosis. Currently it is impossible to predict patients at risk of recurrent attacks, further complicating medical care and intervention.

Our laboratory, one of the world leaders in B cell immunity and atherosclerosis, discovered that pathogenic IgGs generated following an initial MI event are responsible for accelerated atherosclerosis and enhanced risk of recurrent attacks in MI survivors. IgGs can bind to plaque-residing cells to accelerate both lesion cell death and inflammation resulting in vulnerable plaque development and premature MI.

Now we will identify MI-induced IgG and their target lesion proteins. Briefly we will induce an artificial heart attack in mice and isolate spleen B cells activated in response to heart attack. Using molecular biology, recombinant technology and protein expression, recombinant IgGs will be generated. Their target lesion proteins will be identified via immunological methods and mass spectrometry-based proteomic approaches. Finally, ELISA kits will be developed to determine their plasma levels and correlate them with risk of recurrent attacks in heart attack survivors.

Successful completion of the projects will provide new diagnostic tools to predict and identify high-risk patients for further assessment with intensive therapeutic strategies to prevent fatal events. 

Related methods, skills or technologies

This project will expose you to numerous skills and technologies, including:

  • cell culture
  • flowcytometry
  • imaging
  • immunocytochemistry
  • interventions
  • molecular biology
  • PCR
  • preclinical models
  • proteomics
  • Western blots.

This project is suitable for a Masters, Honours or PhD student.

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