Antibiotic Drug Discovery in the Era of Superbugs17 May 2019
Mr Marco Albanese began his work in progress seminar by introducing us to his academic background. Having studied for his masters’ degree in Pharmaceutical Chemistry and Technology at the University of Salerno, Marco currently works on behalf of the Oxford Drug Design company as an early stage researcher and as a PhD student, currently working towards the aim to develop antibacterial solutions for the novel antibiotic targets, histidine sinases.
After the introduction, we were given an overview of the definition of antibiotics, their uses, how they impact our bodies and how our health depends on them. Then, Marco gave us a timeline of how research and development leads to modern medicine and how the evolution of resistance in bacteria has led to the urgent need for new antibiotics. Resistance in bacteria is rising due to the overuse and misuse of antibiotics, with 75% sold for agricultural use and 25% unnecessarily prescribed to patients.
AMR (Antimicrobial resistance), the increasing ineffectiveness of treatments and antibiotics, is a global threat, which leads to 700,000 deaths every year. 42 new antibiotics are in development but, with the stringent FDA regulations that new antibiotics must go through thorough to demonstrate safety and effectiveness only 1 out of 5 will be approved. . This leads to most not reaching the market and with the discovery and funding processes spanning between 9-16 years, it can be a very long and expensive process.
Marco explained the process of his work. The first phase is “Hit Identification”; identifying a molecule and modifying its structure to improve its function. This uses “Fragment Based Drug Design” which involves identifying small compounds that bind to different areas of histidine kinases and then linking them together. Using X-ray Crystallography fragment screening, Marco was able to identify 5 hits which can be optimised to improve interactions with the proteins to improve potency and also reduce binding to unwanted targets, reducing the risk of side effects. Marco explained that by using molecular docking, a binding score would determine the success of the shape that would fill the missing cavity, and this would guide optimization of the hit.
Marco’s docking had been tested with a virtual screening strategy and he showed us examples of the process and outcomes. He finalised his presentation by presenting the conclusions and future perspectives he had drawn from his work, taking into account the discovery costs and process. He hopes to present results on his next work in progress seminar.
In summary, our work in progress speaker, Marco Albanese, gave us a better understanding of his research in antibiotic discovery and the progress needed to implement the solutions. This seminar also gave students and staff the opportunity to benefit from the discussion of ‘Antibiotic Discovery in the Era of Superbugs’, possibly incorporating the new knowledge into their own research.
The Work in Progress seminar series gives postgraduate and undergraduate students anan insight into the range of research projects being undertaken in the School of Computing, an opportunity to broaden their understanding of computer science and identify areas of interest for further study. All are encouraged to attend.
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