Bacteria secrete tiny protein rings that punch through the membranes of rival bacteria, and this fellowship aims to copy that natural weapon to create antibiotics that resistant superbugs cannot evade. Most antibiotics attack bacteria in the same few ways, and many pathogens have evolved to block those attacks. No genuinely new classes of antibiotics have reached patients in 30 years. The problem is that scientists cannot currently measure how these cyclic peptides recognise specific molecules inside the complex, fluid environment of a membrane. This project will develop new chemical tools to watch that recognition happen, then use that knowledge to design synthetic peptides that kill MRSA and other resistant bacteria without harming human cells. If the chemistry works, the result would be antibiotics with a completely new mode of action—drugs that bacteria have never encountered before and have not evolved defences against. That could keep routine surgery safe and protect vulnerable patients from infections that are currently untreatable. The fellowship also includes a public engagement campaign that trains marginalised young people in east London to produce media art about antimicrobial resistance, addressing the social drivers—poor sanitation, precarious work, limited healthcare access—that fuel antibiotic misuse in their communities.
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Antimicrobial resistance (AMR) is currently one of the greatest threats to human health, security and economic stability that the world is facing. Many different species of pathogenic bacteria have now become resistant to the most powerful antibiotics that are available. This means there will be no drugs left to treat “superbugs” such as MRSA: patients, particularly vulnerable ones, will die from life threatening infections such as pneumonia; routine surgical operations will be highly risky; very sick patients receiving chemotherapy will be vulnerable to infection. The O’Neill Report (2016) identified several interventions that are critical to tackling this problem. In this Fellowship I will address two of these: discovering new antimicrobials and effective public awareness campaigns. Most current antibiotics use similar strategies to attack and kill bacteria, and many bacteria have evolved to ward off these attacks. Almost no new antibiotics have been developed over the last 30 years and none have completely new modes of action. I will tackle the challenge of developing novel antibiotics through a programme of fundamental research in the underpinning chemistry and biology. Nature provides inspiration for antibiotics with new modes of action: bacteria kill off other competing bacteria by secreting cyclic peptides – miniature flexible proteins that enter bacterial membranes, recognize specific components and then disrupt the membrane, killing the cell. I will develop new approaches to discover exactly how these cyclic peptides recognize their targets, as currently used methods cannot accurately measure exactly how a cyclic peptide recognizes a membrane component in the complex and fluid environment of a membrane. I will then use this knowledge to make new cyclic peptides that will be more effective antibiotics, killing bacteria that have already developed resistance to the most powerful antibiotics currently used in the clinic without toxic side-effects. Most people have little or no idea about the impact of AMR and how it develops, nor of the role they can play in stopping this. An effective public engagement campaign would have a high impact in reducing the demand for antibiotics and preventing the spread of infection. However, very little is known about how to tailor these messages to particular communities and how to address specific barriers such as access to healthcare, poor sanitation or precarious employment that drive antibiotic misuse. I will develop an ambitious public engagement project focusing on underrepresented and marginalized young people in the Olympic Boroughs (Waltham Forest, Newham, Hackney and Tower Hamlets). I will raise awareness and understanding, communicating the science behind the crisis to these groups and engaging in dialogue to understand the challenges faced by their communities. In collaboration with existing community engagement groups, I will then train groups of young creatives in media and communication technologies. With these tools they will then produce media art that will give them a voice to communicate the crisis and impact of AMR to their communities in their own words.
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