The use of protein structure guided drug redesign to address antimicrobial resistance

Antibiotic resistance is becoming a major problem worldwide. The fluoroquinolones are an important class of antibiotics with widespread use. They are employed to treat a variety of infections, including bronchitis, pneumonia, skin infections, gastroenteritis, sinusitis, urinary tract infections, tuberculosis and typhoid fever. The mechanism of action of fluoroquinolone antibiotics involves inhibition of bacterial topoisomerases. A good proportion of microbial resistance to fluoroquinolones has been shown to arise as a consequence of mutations in the bacterial topoisomerase genes. In this project we will explore the known basis of drug-topoisomerase binding and resistance to design and generate new antibiotic-derivatives aimed at enhancing the fluoroquinolone sensitivity of common drug-resistant mutations. The target novel fluoroquinolone analogues will be designed using available protein-drug structures, including the use of computational assisted drug design. The antibiotic analogues will be synthesized in-house and experimentally tested using biochemistry and microbiology techniques.

The successful should have or expect to have an honours degree at 2.1 or above in Chemistry or Biochemistry. This is a cross-disciplinary project involving elements of microbiology/biochemistry/structural biology and chemical synthesis. Therefore previous experience in these areas is essential.
This is an interdisciplinary project between the Institute of Clinical Sciences, Faculty of Medicine (Prof. Luis Aragon) and the Department of Chemistry, Faculty of Natural Sciences (Dr. Matthew Fuchter) of Imperial College.

Informal inquiries can be made to Prof. L. Aragon ([Email Address Removed]) and Dr. M. Fuchter ([Email Address Removed]) with a copy of your curriculum vitae and cover letter.