Bicyclic peptides: targeting toxins and pathogens to accelerate anti-infective discovery

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project overview:
Infectious diseases are still a global problem, made worse by the growing spectre of widespread antibiotic resistance. This has reduced our options for treatment and means that we need new innovative drugs to treat infections. This includes the need to treat bacterial respiratory and skin infections which produce toxins to cause disease.

It is often argued that the compound collections of pharmaceutical companies are focussed around mammalian targets and lack compounds with structural features typical of successful antibiotics. Here we are looking at a new approach to target and neutralize these toxins and bacteria that cause important diseases including pneumonia and sepsis. These compounds are called Bicycles, and are compounds that are structurally similar to many of the commonly prescribed and highly effective natural product cyclic peptide antibiotics. The chemical variability and ease of identifying those that are potentially effective makes them ideal templates for the design of next generation antibacterial drugs.

With the rapidly growing threat of antimicrobial resistance, such new anti-infective products are urgently needed. This will be done collaboratively between academics at Warwick and our industry partner in Cambridge. The partnership enables student training in a wide range of disciplines involving a range of quantitative experimental approaches across biochemistry, chemistry, microbiology, pharmacology and physics.

Publications

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