CRISPR/Cas9 probing of virulence factors in dermatophytes


   Department of Life Sciences

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

One of the most widespread fungal infections affecting 20-25% of the global population is dermatophytosis. This is caused by fungi that infect the skin, nails, and hair, leading to common conditions such as athlete’s foot or ringworm. Dermatophytosis is uncomfortable and painful, and in at-risk groups, the consequences can be more severe. For instance, in diabetics, fungal infections of the feet may precede the development of foot ulcers which, in turn, may lead to lower-limb amputation. Therefore, given the increase in obesity and accompanying type 2 diabetes, the incidence of more serious cases of dermatophytosis may rise.

Antifungal treatment for dermatophytosis is lengthy, often requiring weeks or months, and there is a high probability of relapse or reinfection. Alarmingly, antifungal resistance is increasing, which could eventually make dermatophytosis untreatable. Therefore, better treatments are needed, but a major hurdle in their discovery is that dermatophytes are poorly understood, and relatively few virulence factors are known.

We have developed a novel ex vivo skin infection model for dermatophytes (Ho et al., 2020), paving the way for exciting discoveries. For instance, utilising this infection model, we identified several polymers with antifungal activity (Ho et al., 2021).

In this project, we aim to unravel the secrets of virulence factors behind these fungal infections utilising this model. First, we aim to identify virulence factors by determining which genetic factors are specifically overexpressed during infection, using techniques such as RNAseq. Next, using CRISPR/Cas9, a powerful genome editing technology, we will create fungi that lack these virulence factors and then investigate their importance using the infection model.

Thus, the main outcome of the project is to identify potential therapeutic targets, thereby developing a platform for developing novel antifungal compounds.


Biological Sciences (4)

Funding Notes

This is for self-funded students only, e.g. those that have funding from their own government or institute, or those that have other means of supporting their studies.

References

Ho, F.K.H., Belgado-Charro, B., Bolhuis, A. (2020) Evaluation of an explanted porcine skin model to investigate infection with the dermatophyte Trichophyton rubrum. Mycopathologia. 185 (2):233-243
Ho, F.K.H., ., Bolhuis, A. Belgado-Charro, B(2021) Prevention and treatment of fungal skin infections using cationic polymeric films. Pharmaceutics 13:1161.

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