James Law

Antibiotic resistance is on the rise, with more pathogenic bacteria becoming resistant to higher doses of antibiotics. One major contributing factor is biofilm formation, in which a colony of bacteria forms a protective layer of molecules that protect it from external threats and increase its resistance to antibiotics by up to 1000-fold.

Part of this biofilm structure is extracellular DNA, which serves as a scaffold supporting the biofilm. The protein Integration Host Factor (IHF) has been identified as the glue that binds the extracellular DNA duplexes together. However, IHF is known as a DNA-bending protein found within the genome, shown to reduce DNA entanglement, not a DNA-stabilising protein that would reinforce entanglement.

One clue comes from the different pH environments; genomic pH is around neutral, whereas biofilms are acidic. This difference in acidity may play a crucial role in explaining the inconsistency seen in its behaviour.

My project aims to investigate this by examining IHF's interactions with two DNA strands at pH 7, 5.5, and 4.5 at the atomic level using molecular dynamics simulations.

What are the key results of your project?

• I was able to show how pH changes IHF’s affinity to bridge.
     • In low pH, IHF exhibits strong bridging behaviour.
     • In neutral pH, IHF switches into a translocation mechanism, moving from one DNA strand to the next.
• My research in uncovering the nuance in IHF's behaviour will contribute towards developing drugs against antibiotic resistance.
• This internship has given me the ability to answer questions no one knew the answer to and meaningfully contribute to the scientific and wider community.
• Before starting this internship, I had very limited coding skills. However, over the past 20 weeks, I have developed a range of coding skills that have enabled me to use multi-GPU processing to perform over 15 large simulations, along with creating all the necessary scripts for data analysis.