Early Career Fellowship (CJ Martin - Overseas Biomedical Fellowship): The biological impacts of nanoparticle interactions with proteins (2013–2017)

Abstract:
A-Home: Synopsis: Once a nanoparticle enters a biological fluid, the nanoparticle will interact with a mixture of proteins forming a nanoparticle-protein complex. The further biological response of the body is influenced by the nanoparticle-protein complex, as bound proteins are able to bind to receptors on cell surfaces, mediate the uptake of the nanoparticle into the cell, activate intracellular signalling, or illicit immune responses. The proposed research will investigate the biological significance of the nanoparticle-protein interactions, while providing a novel strategy for better assessing the biological properties of nanoparticles. In this study, a library of specifically engineered nanoparticles of different sizes and surface characteristics will firstly be synthesized to allow a systematic investigation. Next, the protein binding profiles of these nanoparticles in the plasma will be identified using a quantitative proteomics approach. At the mean time, a high-throughput screening strategy will be carried out to determine the biological effects of these nanoparticle-protein complexes, such as interactions with cell surface, during endocytosis and in cellular organelles, as well as their effects on biodistribution and clearance. The obtained data will be processed and input into bioinformatics tools to identify the key nanoparticle-bound proteins that elicit significant biological responses. Finally, proteins that present interesting targeting or cell activation properties will be selected to modify the nanoparticle surface for therapeutic applications. This study is expected to significantly expand our current understanding on how nanoparticles interact with cells and tissues, while providing valuable insights to the molecular mechanisms. It will also establish a novel methodology for assessing the biosafety of new nanomaterials, as well as for designing safer and more efficient nanoparticles in therapeutic applications.
Grant type:
NHMRC Training (Postdoctoral) Fellowship
Funded by:
National Health and Medical Research Council