Drug Delivery Disposition and Dynamics
Our research involves designing and developing the next generation of drug delivery systems to enhance the effectiveness of medicines.
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Darren Creek | Discovery of new drug targets for malaria
Malaria and Sleeping sickness (Human African trypanosomiasis) are tropical diseases of developing countries that are caused by protozoan parasites. The infections are transmitted by fly or mosquito vectors, and are fatal if untreated. Current treatment options are unsatisfactory due to toxicity, emerging resistance and impractical administration requirements in resource-poor tropical countries. There is a pressing need to discover new drug targets to facilitate the development of new medicines for malaria and HAT. Protozoan parasites possess many unique genes and metabolic pathways that enable the parasite to survive in the diverse nutritional environments of the insect vector and the mammalian host. The aim of this project is to discover unique aspects of parasite and host metabolism that will enable discovery of new and safer drugs.
This project will utilise advanced LC-MS based metabolomics technologies in combination with bioinformatics and biochemical studies to elucidate interactions between antiparasitic compounds and metabolic pathways. The specific aims of this project are:
1) to identify novel roles for genes of unknown function,
2) to characterise novel metabolites and determine metabolic pathways responsible for their production, and
3) to identify drug targets for novel antiparasitic compounds.
Research Placement
Opportunities are available for student placements in collaborating labs either in Australia, US or Europe, and field placements may also be available at clinical sites in Africa and South-East Asia.
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Angus Johnston | Using nanotechnology to unlock the secrets of biology
Nanoengineered drug carriers have the potential to revolutionise the treatment of a number of diseases. For maximum therapeutic efficiency, drugs not only need to be delivered to the right cells, but to the specific compartments within these cells where the drug is active. The aim of this project will be to understand the mechanisms of nanoparticle trafficking in cells using a combination of high-resolution fluorescence microscopy, live cell imaging and functional fluorescence assays. You will also work on functionalising nanoparticles to control their trafficking and localization within the cell.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Angus Johnston | Engineering the next generation of nanoparticle drug carriers
There have been significant advances in the treatment of diseases such as HIV, flu and cancer using nanoparticle therapies, however there is still a way to go before we have the optimal drug delivery system. The next generation of nanoparticle drug carriers will need to respond intelligently to biological stimuli to target the drugs where it is required. The aim of this project will be to develop self-assembled nanoparticles loaded with proteins and DNA and to engineer the release of the cargo precisely inside the cell. The project will involve polymer synthesis, materials characterization and live cell fluorescence imaging.
The project will focus on engineering nanoparticles in Dr Johnston’s lab, and will also involve working with Dr Georgina Such from the University of Melbourne synthesising polymers.
There will be an opportunity for an extended visit to an international laboratory in the 2nd or 3rd year of the project. The visit will last for 2-5 months and the location of the visit will be determined once the project is finalised.
Students would engage in three lab rotations in Year 1 prior to selection of a project and supervisory team. The intention is that students are not fixed on a specific project in the initial stages of the program but rather select from a program where three laboratory sabbaticals with different Main Supervisors are offered. At the end of the rotations the student will discuss the options with the Supervisors and course co-ordinator and a decision made as to the project selected for the PhD.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Cornelia Landersdorfer | Developing an approach towards personalised medicine against ‘superbugs’
For many decades, a ‘one-size-fits-all’ approach has been used for the dosing of antibiotics as single agents or multiple antibiotics in combination therapy. This is increasingly ineffective and has facilitated the emergence of ‘superbugs’ that are resistant to all antibiotics. New antibiotic development has been in decline. Therefore, it is vitally important that the dosage regimens of available antibiotics are optimised to save patients’ lives and preserve antibiotic activity for the future.
Our projects combine dynamic in vitro infection experiments that expose bacteria to antibiotic concentration-time profiles as seen in patients, molecular and genomic studies of mechanisms of action and resistance of antibiotics, clinical pharmacokinetic studies and development of novel mathematical models to optimise treatments for patients.
Projects include flexibility for students to spend the majority of their time undertaking experimental work in our laboratories, or performing mathematical modelling, or a combination of both. The research involves collaborations with microbiologists and clinicians. Students with academic backgrounds in pharmaceutical sciences and/or pharmacy and/or microbiology and/or mathematical modelling are encouraged to apply.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Cornelia Landersdorfer | Rationally optimised antibiotic dosing strategies to target resistant bacterial 'superbugs'
‘Superbugs' resistant to all available antibiotics in standard monotherapy are among the most serious threats to human health. At the same time there is a lack of new antibiotics. Individualised, precision antibiotic dosing strategies in optimised monotherapies or combinations provide a tangible and highly promising option to combat 'superbugs' by achieving maximised bacterial killing and suppression of resistance.
Research Placement
Antibiotic dosing strategies will be rationally optimised based on pharmacokinetic/pharmacodynamic principles and bacterial characteristics. This incorporates designing and performing static and dynamic bacterial in vitro experiments (including in the dynamic hollow fibre in vitro infection model which can simulate antibiotic concentration time profiles as observed in patients), population pharmacokinetic/pharmacodynamic and mechanism-based mathematical modelling and potential other approaches. A proportion of the studies would be conducted either at the laboratory of Dr Gauri Rao, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC), or at other collaborating laboratories in bacterial omics at the Monash Parkville or Clayton campus.
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Michelle McIntosh | Formulation development with industry partners
Working in the Medicines Manufacturing Innovation Centre on a project designed with an industry partner. This project may involve developing and characterising an inhaled delivery system, a controlled release oral formulation or a device and therapeutic combination product.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Joseph Nicolazzo | Restoring blood-brain barrier homeostasis for the treatment of Alzheimer’s disease
The blood-brain barrier exhibits various biochemical changes during Alzheimer’s disease that lead to impaired removal of toxins from the brain or impaired brain uptake of nutrients essential for cognition. Our research has identified that the levels of certain blood-brain barrier transporters and carrier proteins are reduced in Alzheimer’s disease and restoring their levels may open up novel therapeutic opportunities for Alzheimer’s disease. Using a host of in vitro and in vivo approaches, this project will identify novel approaches to reverse these biochemical changes, ultimately leading to improved cognitive function in Alzheimer’s disease.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Jie Tang | Engineering biomimetic nanoplatform for mucosal delivery
Nanomaterials offer transformative potential in the development of advanced delivery systems for a wide array of pharmaceutical and biomedical applications. This research program aims to harness these opportunities, benefiting the pharmaceutical industry and healthcare sector. We are focusing on creating a versatile biomimetic drug delivery platform utilizing nanoparticles with engineered morphology and architecture. These nanoparticles are designed to emulate gut microbes, facilitating enhanced mucus penetration and transcytosis through the intestinal or respiratory epithelium. This approach aims to significantly improve the delivery efficiency of large biomolecules, including pDNA, mRNA, and proteins.
Key areas of investigation include:
- Nanoparticle-Cell Interactions: Understanding the interactions between nanoparticles and specific epithelial cells to optimize delivery mechanisms.
- Enhanced Mucus Penetration: Developing nanoparticles that can effectively penetrate the mucus layer to reach target sites within the intestine or respiratory system.
- Transcytosis Mechanisms: Exploring how nanoparticles can be engineered to cross the intestinal/respiratory epithelium more efficiently.
- Oral Vaccine Development: Designing nanoparticles to enhance the efficacy of oral vaccines, potentially improving infection control and cancer prevention, particularly for diseases like colorectal cancer.
The expected outcomes of this program include the development of more effective delivery systems that can lead to better therapeutic outcomes, improved vaccine performance, and advancements in pharmaceutical applications.
Projects within this program may involve:
- Synthesizing and characterizing nanoparticles with specific morphological features.
- Investigating the biological interactions and pathways of nanoparticles in in vivo or ex vivo intestinal models, such as organoids-derived monolayer models.
- Evaluating the efficacy of nanoparticle-based delivery systems in preclinical settings.
- Designing and testing novel oral vaccines leveraging the developed nanoparticle platforms.
By contributing to this program, students will gain hands-on experience in cutting-edge nanotechnology, immunotherapy, and drug delivery research, preparing them for impactful careers in both academia and industry.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Natalie Trevaskis | Targeting toxic gut lymph to treat acute disease
Acute and critical illness (ACI) are usually managed in emergency and intensive care settings, and includes sepsis, trauma, haemorrhagic shock and pancreatitis. 30% of patients die due to progression of ACI from an acute systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS). Current management of ACI is supportive and includes fluid resuscitation, enteral feeding, antibiotics and organ support. More effective and specific treatments are critically needed.
Recent findings in our collaborators lab have identified gut-lymph as a source of toxic factors that promote SIRS and MODS. According to the gut-lymph hypothesis blood flow to abdominal organs is reduced in ACI. This results in gut ischemia and breakdown, and the release of toxic factors that drain into the gut-lymph. Toxic gut-lymph flows into the thoracic lymph, bypasses the liver and enters the systemic circulation via the subclavian vein. Toxic gut-lymph subsequently damages vital organs remote from the gut.
The project aims to:
1. Develop novel drug delivery systems to target gut-lymph to treat ACI
2. Demonstrate that gut-lymph targeted delivery systems facilitate improved treatment of experimental ACI
This project addresses the need for effective and disease-specific treatments for ACI via the development of approaches to treatments that target ‘toxic’ gut-lymph.
Research Placement
The student may spend up to 4 months working in the labs of our collaborators Prof John Windsor and Anthony Phillips at the University of Auckland, running experiments in ACI models.
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Natalie Trevaskis | Targeting lymph-fat interactions to develop new treatments for diabetes
There is a global epidemic of obesity, insulin resistance (IR) and type 2 diabetes (T2D). Excess abdominal fat increases the risk of IR and T2D but the reasons are not completely understood. The intestinal lymphatics flow through abdominal fat. Recent studies from our lab have demonstrated that in obesity lymph fluid 'leaks' from intestinal lymph vessels leading to fat expansion and changes that promote IR.
This project aims:
1. To confirm the potential to treat IR/T2D through targeted modulation of lymph content and/or lymph access to abdominal fat
2. To identify the components of lymph that promote changes in fat function leading to IR
The studies will advance understanding of the mechanisms that drive IR/T2D and inform the design of improved treatments for obesity, IR and T2D.
Research Placement
Undertake a placement of a defined period in an external institution, either domestic or international, gaining experience in a different research environment that will augment your PhD.
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Nicolas Voelcker | Wearable nano-biosensors
This research project will extend the capability of our nanotechnological platforms and electrochemical bionsensing capabilities towards a wearable patch that enables non-invasive, pain-free sampling of sweat and interstitial fluid for the monitoring of physiological events and the diagnosis of diseases.
The project aims to develop a nanostructured electrochemical biosensor based on silicon nanomaterials. Using silicon nanoarchitectures, we seek to develop, optimise and validate wearable biosensors able to detect metabolite levels (glucose, lactate) and, ultimately, proteins such as interleukins, tumour necrosis factors and neuropeptides, as their levels remain significantly similar in plasma and sweat. This biosensing platform will provide a novel approach for addressing the current challenges in reliable diagnostic biosensors that can be integrated onto wearable device platforms.
Research Placement
This project provides the opportunity for a placement at the Max Planck Institute for Medical Research in Heidelberg, Germany.
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Nicolas Voelcker | Targeted nanocarriers for cancer therapy
Porous silicon nanoparticles are very promising as a drug carrier thanks to their high porosity, biodegradability and biocompatibility. This project will explore the application of these nanocarriers to deliver chemo, gene and/or immune therapy to treat cancers using a range of preclinical cancer models including humanised tissue engineered cancer models that are highly predictive of performance in the clinic.
Research Placement
Placements at QUT in Brisbane for the humanised cancer model are offered.