Development of future nanomedicines to inhibit pathological formation of amyloid plaques in amyloid disease

 Supervisor Professor Thomas Davis, Dr Ibrahim Javed & Dr Aleksandr Kakinen

Toxic misfolding and aggregation of the proteins is the underlying pathological paradigm for different neurological diseases such as Alzheimer’s (AD) and Parkinson’s diseases (PD) and metabolic disorders like type-2-diabetes. Amyloid diseases are more prevalent with age and often associated with several underlying pathologies. Deposition of fibrillar plaques in the tissues correlates with neurodegeneration and cognitive dysfunctions in AD and PD while loss of insulin-producing β-cells in type-2-diabetes. The development of biocompatible nanomaterials has become a new frontier in the detection, treatment and prevention of human amyloid diseases. Researchers have investigated the interaction between amyloids and various classes of nanoparticles for controlling protein aggregation. This project aims to develop novel smart biocompatible nanomedicines to inhibit pathogenic amyloid plaque formation in AD, PD and type-2-diabetes using in vitro and in vivo disease models.

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Understanding the effect of gut-bacterial amyloids on amyloid plaques formation in Alzheimer’s disease

 Supervisor Professor Thomas Davis, Dr Ibrahim Javed & Dr Helen Forgham

Alzheimer’s disease (AD) is one of the leading causes of dementia with tremendous socioeconomic impact. Despite AD is becoming more prevalent as the population ages, yet the mechanisms that lead to synapse destabilization and neuron death remain elusive. Deposition of fibrillar tangles and amyloid plaques in the brain derived from the aberrant aggregation of tau- and amyloid-β (Aβ) peptides correlates with neurodegeneration and cognitive disfunctions in AD. Notably, gut bacteria produce similar amyloid structures to support their biofilms. The interaction between bacterial amyloid fibril and Aβ has been hypothesized to accelerate AD symptoms. This project aims to study the interaction of bacterial amyloids with Aβ peptide. Potential strategies include investigation of cross-seeding, aggregation kinetics and fibril structural rearrangements of hetero-amyloid formations.

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Translocation of bacterial amyloids from gut to the brain and its implications in neurodegenerative disease

 Supervisor Professor Thomas Davis, Dr Ibrahim Javed & Dr Helen Forgham

Deposition of fibrillar tangles and amyloid plaques in the brain derived from the aberrant aggregation of tau- and amyloid-β (Aβ) peptides correlates with neurodegeneration and cognitive disfunctions in Alzheimer’s Disease (AD). Notably, gut bacteria produce similar amyloid structures to support their biofilms. The interaction between bacterial amyloid fibrils and Aβ has been hypothesized to accelerate AD symptoms. Certain bacterial proteins have potential to induce gaps in gastric epithelial cells. This can result in leak and transportation of gut-bacterial products into the blood or lymphoid tissues, and then to the brain. This project aims to study translocation of bacterial amyloids from gut to the brain using in vitro gastric epithelial cell model.

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Development of novel nanomedicines against bacterial amyloids

 Supervisor Professor Thomas Davis, Dr Ibrahim Javed & Dr Aleksandr Kakinen

Bacterial biofilms are formed by bacterial colonies to protect their integrity, quorum sensing, inter and intra colonial communication and to hinder the access of antibacterial drugs to the underlying bacterial cells. This further leads to the development of multidrug resistance, that is a global pandemic. The bacterial amyloids provide scaffolds for the deposition and strengthening of biofilms. Nanomedicine can provide opportunities to inhibit the bacterial amyloids and biofilms to enable the re-supply of antibacterial drugs to bacterial cells, addressing multidrug resistance and pathological implications of bacterial amyloids.

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What to do

  1. Review each project description and find one which matches your areas of interest.
  2. Contact the research group leader or project advisor directly to discuss the project and arrange a meeting or visit to the AIBN lab.

Contact 

If you have general enquiries about studying at AIBN please contact our HDR team.
hdr.aibn@enquire.uq.edu.au

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