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 CONSIDER JOINING US!

The following projects are available in the Carter lab. These are currently designed as one-year honours projects to be undertaken after a BSc, however some could be expanded to MSc or PhD projects. If you would like further information about any of these projects please contact Dee Carter.

Manuka honey has unique antimicrobial properties that are due to methyl glyoxyl (MGO), derived from manuka nectar. However, many other honey types are antimicrobial due to the presence of glucose oxidase (GOX), a bee-derived enzyme that oxidises glucose to gluconic acid and hydrogen peroxide (H2O2). High GOX/H2O2 activity is generally not clearly associated with floral source, and a given source may yield honey with high, low or no activity.  There is emerging evidence that GOX production instead aligns with bee health, and that the capacity to produce GOX, and therefore H2O2 in honey, conveys health and protection from disease on the beehive.  Furthermore, it appears bees that forage on a diverse diet that is derived from rich and varied flora have increased GOX levels. The summer fires in NSW devastated the beekeeping industry, which is now looking for the best way to rebuild. This project aims to produce data on the value of biodiverse forests and champion regeneration rather than producing plantations, with a recognition that healthy forests mean healthy bees, which in turn mean active honey. We will work with NSW beekeepers to assess microbiota and enzyme levels in bees and hives from highly disturbed and undisturbed regions using metagenomic and protein purification approaches, and determine the antimicrobial activity of the honey these bees and hives produce.

Understanding how biodiversity and bee health affect antimicrobial honey

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This project is part of a collaboration with Dr Emily Remnant (SOLES, USYD) and with Professor Liz Harry and Dr Nural Cokcetin at UTS.

We all know of the problems associated with antimicrobial resistance in bacteria. What is less well known is that fungi are also evolving resistance to antifungals. Fungi can’t pass resistance elements around like bacteria, making multidrug resistance less likely, however there are very few antifungals available so even becoming resistant to a single antifungal class can be a significant problem. Aspergillus flavus is a common soil fungus in warm regions and it can cause post-harvest contamination of food, particularly corn and peanuts.  It can also be an opportunistic pathogen of people, causing sinus, lung and occasionally invasive infections.  Many food crops are treated with azole-based fungicides that have a similar mechanism of action to medical azole drugs. The use of these fungicides is particularly high in countries like Vietnam, and we have found surprisingly high levels of resistance to medical azoles in A. flavus isolates from Vietnamese crops and soils.  We are now interested in determining whether this resistance has arisen recently due to increased fungicide use, or whether it has been around for a long time but had never been tested. We have a set of isolates obtained from Vietnam in 2000 with accompanying microsatellite data that we can use to address this question. In this project we will test these older isolates for antifungal resistance, and type our newer azole-resistant isolates with the same microsatellite markers. We will also look at areas of the A. flavus genome that may be associated with azole resistance to see if we can find the underlying mechanisms of resistance. From this we will determine the relationship between these two sets of isolates, the likely drivers of resistance and the potential molecular mechanisms that underlie it.

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This project will be undertaken in collaboration with Dr Justin Beardsley at the Westmead Hospital Millennium Institute.

Emergence of antifungal resistance in a pathogen of plants and people

The use of cold plasma to kill fungi

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Cold plasma is a new method that uses high voltage electricity to generate reactive species capable of killing microbial pathogens.  This technology is particularly promising in the area of food safety, as it can be used to sterilise food surfaces without leaving any toxic residues.  It also has potential applications in medicine for sterilising reusable PPE such as face-masks and for cleaning equipment that has become contaminated with problematic pathogens. In this project we will work with surrogate viruses for norovirus and coronavirus and with the yeast pathogen Candida auris to determine if cold plasma can deactivate these micro-organisms.  This work has the potential to improve safety and reduce waste in food production and clinical medicine.

This project will be undertaken in collaboration with Dr Anne Mai-Pracnow and Prof. Patrick Cullen in the Faculty of Engineering at USYD.

Picture credit: Dr Mai-Anne Pracnow

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Micro-cell variants in the yeast pathogen Cryptococcus and their role in infection

Micro-cells occur in some strains of the yeast pathogen Cryptococcus when it is under the same stresses that are present in human infection.  These cells are about 1/10 the size of normal cells, and they appear to have normal cell walls and capsule and they contain DNA. We have a set of very closely related strains of Cryptococcus that vary in virulence and in their ability to produce micro-cells. Interestingly, micro-cells appear to be more common in the more virulent strains. When we looked for their presence in a set of clinical isolates that had caused meningitis, we found they were correlated with increased intracranial pressure in HIV-AIDS patients. Their small size also suggests that they may have a role in dissemination. Very little is currently known about them, however, and cause and effect are not clear.  In this project we will perform a detailed analysis of our set of closely related strains to determine 1) what triggers microcell production in some strains; particularly the stresses associated with human infection such as high temperature, low nutrients and drug treatment; 2) whether the number of micro-cells changes over time and throughout the growth phase of the culture; and 3) whether micro-cells represent a set of viable cells that are capable of becoming normal sized cells under appropriate conditions.

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Regular cells of Cryptococcus and micro-cells

The production of morphologically altered Cryptococcus cells in response to stress

Growth in the mammalian host can be stressful for fungal pathogens. We have found some strains of the yeast pathogen Cryptococcus respond to this by developing unusual cellular morphologies. These may be damaged and weakened cells, or they may be adapted cells that can survive stress in a dormant state. In certain strains these cell types appear to be associated with prior antifungal therapy and relapse of the host, suggesting a persister-type phenotype. They may also be what is known as a “viable but non-culturable cell” (VBNC), which is a cell type seen in a range of microbes that enables long-term survival in a state of reduced metabolism. A previous honours student found different Cryptococcus strains formed quite distinctly different unusual cells and that these responded to host-related stresses (high temperature, low nutrients and elevated CO2) in different ways. The aim of this project is to examine these different morphological types in detail using microscopy, microbiological growth dynamics, cellular probes and molecular methods. From this we aim to understand how Cryptococcus survives in the host – sometimes for many years – before becoming a disease-causing invasive pathogen.

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Stressed-out Cryptococcus cells

Understanding antifungal drug synergy and antagonism

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Fungal infections are on the rise and there is an urgent need for new antifungal therapies. There are few antifungals currently on the market and resistance is a growing issue. However, as fungal cells are similar to mammalian cells it is very difficult to find an antifungal target that does not also harm the host. New approaches to finding antifungals are therefore gaining popularity. One approach is to use a secondary agent to improve the action of an existing antifungal – a system known as drug synergy. We have found certain iron-chelating molecules can improve the action of some antifungals, however there can be a dark side to this as sometimes these reduce the action of the antifungal – a system known as antagonism. In a previous study we found a certain drug-chelator combination was synergistic in some fungal strains but antagonistic in others. When we performed a transcriptomic study of these strains we found a number of potential antifungal pumps were upregulated, suggesting some stresses may induce cross-protective mechanisms that end up pumping out both agents. The aim of this study is to probe more deeply into this data and validate the synergistic and antagonistic responses using Q-PCR and probes for oxidative stress. The outcome will be a molecular basis for unexpected drug interactions..

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