NTU's Fully-funded PhD Studentship Scheme 2022
Project ID: S&T74
Clinically relevant staphylococci are increasingly multi-drug resistant, with clinical isolates of species such as Staphylococcus aureus frequently susceptible to only antibiotics of last resort. Antimicrobial-resistant pathogens currently cause more than 700,000 deaths per year, which could increase to 10 million deaths per year by 2050, more than from cancer and diabetes combined. With few novel antimicrobials being developed, much research has focused on alternatives to antibiotics, such as phage therapy. However, instead this project will seek to reclaim antibiotics deemed to no longer be effective due to widespread resistance, by using small-interfering RNAs (siRNAs) to down-regulate bacterial genes that confer resistance to these antibiotics. In addition, we will seek to prevent expression of genes encoding bacterial virulence factors, particularly those involved in biofilm formation which is the main mechanism of disease for many staphylococcal species.
Small-interfering RNAs are short strands of RNA, ~25 nucleotides in length, that bind to mRNA of the target gene and prevent its translation into a functioning protein. Through whole-genome sequencing, our knowledge of genes involved in antibiotic resistance has grown significantly, to the point where for many bacterial species we can accurately predict the antibiotic resistance profile of a strain, just from its genome. This understanding of resistance mechanisms should allow us to design siRNAs to target individual bacterial genes to down-regulate their expression, and so result in isolates that are once again susceptible to the relevant antibiotic. Utilizing a collection of clinical staphylococcal isolates, we will seek to test a range of siRNAs against multiple antibiotic resistance genes.
Following the design and testing of effective siRNA in broth culture, the project will develop to test the effect of siRNAs in both an in vitro gut model and a catheter model of infection. In addition, as for any novel therapeutic approach, it is common to test how quickly bacteria can adapt to overcome the intervention. We will perform a continuous culture evolutionary experiment to determine if staphylococci can adapt to the presence of siRNA and identify the mutations required.
Overall, the project will allow the development of skills in Illumina and Nanopore-based whole-genome sequencing, siRNA design, molecular techniques such as cloning, and the use of in vitro models of infection.
School strategic research priority
The project aligns directly with the research programme of the CHAUD research centre (Centre for Health, Ageing and Understanding Disease), namely “developing methods and materials (including bio-inspired compounds) to use as potential drugs to investigate biological processes and structures”.
For the eligibility criteria, visit our studentship application page.
How to apply
For guidance and to make an application, please visit our studentship application page. The application deadline is Friday 14 January 2022.
Fees and funding
This is part of NTU's 2022 fully-funded PhD Studentship Scheme.
Guidance and support
Download our full applicant guidance notes for more information.