Tiralongo Group

Supervisor: Prof Joe Tiralongo

Materials Science, Nanotechnology, Interaction Biology, Glycobiology, Biochemistry

Micro-technologies in the form of Micro-Electro-Mechanical Systems (MEMS) and micro-plasmonics platforms offer the potential for high-resolution, high-throughput label-free sensing of biological and chemical analytes. Silicon carbide (SiC) is an ideal material for augmenting both MEMS and plasmonics routes, however such inorganic surfaces need to appropriately and efficiently functionalised to allow subsequent immobilisation of functional biomolecules. To this end we trialled various organosilane-based self-assembled monolayers for the covalent functionalisation of 2-dimensional SiC films, and have now developed an affordable, facile one-step method. Using high-throughput glycan arrays as our model system a novel platform that has the potential to combine established array technology with the label-free capabilities of MEMS or plasmonic systems is one step closer. Using a similar functionalisation route, we have extended the use of organosilanes to biofunctionalise the surface of 3-dimensional nanoparticles, specifically carbon dots. Carbon dots are cheap, biocompatible, chemically stable, heavy-metal free quantum dots, of low toxicity that offer an alternative approach for bio-imaging and -sensing applications. Again, employing glycans as our model system, we are now using our biofunctionalisation approach to generate glycan-coated carbon dots that we are using to explore complex glyco-interactions.

Techniques: Organic chemistry; surface plasmon resonance, microarray technology, flow cytometry, microscopy

Supervisors: Prof Joe Tiralongo & Dr Darren Grice

Separation Chemistry, Immunology, Glycobiology

Mushrooms are increasingly attracting attention for their immuno-modulatory activities, which are primarily due to b-glucans. b-Glucans comprise a group of glucose (Glc) polysaccharides that are chemically diverse, with a common b-glucan being cellulose (b-(1,4)-linked Glc. It is non-cellulosic b-glucans, mainly b-(1,3)-linked Glc that have been shown to be potent immunological stimulators in humans, and some are now used clinically in China and Japan, as well as being commercially available in Australia.

Due to the complexity of b-glucan chemistry and structure a detailed understanding of the mechanism of action, specifically the structural components that dictate specific immunological responses, are yet to be fully resolved. In collaboration with Integria Healthcare, the overall objective of the project is to explore the immuno-modulatory effects of mushroom b-glucans, specifically the project aims to structurally characterise commercially available mushroom polysaccharides rich in b-glucans and correlate this with their associated immuno-modulatory effects The outcomes from this project will lead to a clearer understanding of the properties of b-glucans associated with commercially available mushroom polysaccharides that induce specific immuno-modulatory effects.

Techniques: Carbohydrate chemistry, ELISA assays, separation chemistry, polysaccharide structure determination

Supervisors: Assoc Prof Thomas Haselhorst and Prof Joe Tiralongo

Structural Biology, Computational Chemistry, Microbiology, Cell Culture, Molecular Biology, NMR spectroscopy

Project details: The opportunistic human pathogenic fungus Aspergillus fumigatus causes severe systemic infections including Invasive Aspergillosis (IA), a major cause of life-threatening fungal infections in immuno-compromised patients. An over-whelming number of reports appeared in 2020 demonstrating that COVID-19-associated pulmonary Aspergillosis (CAPA) is one of the leading factors affecting morbidity in critically ill COVID-19 patients [2] with some reports even classifying Aspergillosis as a significantly under-recognized ‘Superinfection’ in COVID-19.

Drug resistance among fungal pathogens is continuing to develop into an increasingly serious threat to public health and health-care systems worldwide. This PhD projects entails the development of novel antifungal therapies that are urgently needed using our established and unique combined in-silico/SPR drug discovery pipeline evaluating a number of new protein targets.

Techniques: Computational Chemistry including visualisation and molecular docking, in-silico screening, microbiology, protein expression, drug discovery and design.

Supervisors: Dr Erik W Streed & Prof Joe Tiralongo

Biophysics

Techniques from physics have often been adapted to solve problems in the life sciences. Notable examples include microscopy, x-ray diffraction, and fluorescent labelling. We are interested in developing new ways to investigate the properties of cells, subcellular structures, and large biomolecules using ion trapping techniques from quantum physics. Project students will be involved in a subset of the following project aspects: culturing and fluorescent labelling of yeast cells, loading yeast cells into an ion trap, and then measuring the physical properties & manipulating the cell using electrical, hydrodynamic, and laser methods. There are also projects available on mathematical modelling of the particles.  Physics or Biological laboratory course experience preferred for in-lab components.

Supervisors: Dr Chris Day, Prof Joe Tiralongo, Dr Alison Peel & Assoc Prof Daniel Kolarich

Glycomics, glycoproteomics, infection, evolution, zoonotic disease

Animals such as bats are considered prime hosts for zoonotic diseases before they "jump" to humans. Viruses such as influenza or COVID-19 are known to infect different host species, where they can gain novel functions and increase their virulence.

The cell surface of mucosal barriers in the respiratory tract plays a fundamental role in this interplay. This cell surface, but also any body fluid proteins are extensively modified with species specific sugars called glycans. These glycans build a universal language used by cells but also abused by pathogens. Though eukaryotic organisms share one alphabet, evolution made them speak multiple different languages and dialects. We have developed glycomics & glycoproteomics tools to translate these languages and uncover how pathogens learned to speak and interpret glyco-languages between different species. Understanding this relationship is crucial as viral, bacterial and parasite pathogens have developed elaborate strategies to jump between hosts – and many of these strategies involve cell surface glycans. The influenza virus is just one fairly well understood example that uses this strategy.

As part of this project several student projects are available that include 1.) characterisation of the plasma/serum glycome across several vertebrae species; 2.) investigation and understanding cross-species recognition of pathogen adhesins; 3.) novel, cutting-edge science to understand the role of glycosylation and infection in flying foxes;

4.) working in and with an interdisciplinary and international team delivering first-hand knowledge and skills in a variety of biochemical and immunological skills and techniques.

The outcomes of these highly collaborative (across Griffith, national and international partners) projects will provide novel clues how infectious diseases can spread and uncover novel targets to stop their distribution and uncover novel biology in animal species of primary interest for the distribution of zoonotic pathogens. Students will be introduced to biochemistry and immunology laboratory workflows that include (but are not limited to) SDS-PAGE, Western blotting, Proteomics and Glycomics sample preparation, acquisition and data analyses and gain general knowledge in Biochemistry, Glycobiology and Immunology.

Techniques: mass spectrometry, glycomics, proteomics, microarray, Immunoglobulins, protein purification, immunological techniques.

Supervisors: Dr Larissa Dirr, Dr Alpesh Malde, Prof Joe Tiralongo, Prof Mark von Itzstein, Assoc Prof Daniel Kolarich

Glycoproteomics, biochemistry, signaling, protein structure

Receptor glycoproteins are highly important signalling molecules in controlling cell communication and interaction. Dysregulation of these signalling pathways is frequently associated with diseases such as cancer and chronic inflammatory conditions. However, the role their glycosylation plays for protein structure and interaction is still poorly understood.

Type III family of receptor tyrosine kinases such as c-KIT (also known as SCF receptor or CD117 PDGF-receptor-a and b, CSF-1 receptor and the FLT3 receptor play a vital role in the pathogenesis across different types of cancer.

As part of a larger project a variety of student projects are available that include aspects of mass spectrometry applications (proteomics, glycomics and glycoproteomics) next to protein structure, cell culture, Western Blot, electrophoresis and other standard biochemistry techniques. In combination these techniques are being employed to characterise and modulate the glycosylation of these important signalling molecules to understand how protein-specific glycosylation impacts protein function and cell signalling. This knowledge will provide opportunities for developing novel therapeutic strategies targeting these receptor proteins. As part of this project, students will be introduced to biochemistry laboratory workflows that include (but not limited to) SDS-PAGE, Western blotting, Proteomics and Glycomics sample preparation, acquisition and data analyses and gain general knowledge in Biochemistry and Glycobiology.

Techniques: mass spectrometry, glycomics, proteomics, cell culture, Western blotting, protein structure, basic biochemical workflows.