JPIAMR 14th Call Partner Search Tool

General Information

• Project title: Translating resistance breakers in vivo
• Type: Project looking for partner
• Organisation: University of Oxford
• Country: United Kingdom (UK)

Research area

• Scientific area(s) of the call:
  1. Improvement of drug/plant protection agent efficacy and/or specificity through chemical modifications (including hit to lead optimisation)
  2. Drug/plant protection agent repurposing
  3. Optimisation of drug/plant protection agent combinations, alone or with adjunct therapies (including therapeutic vaccines)
  4. Design and implementation of new strategies (including optimisation of drug doses) for improved application, efficacy and delivery of single or combinations of antimicrobials
  5. Design and implementation of innovative tools, including novel chemistry and/or new materials for improved application, efficacy and delivery of antimicrobials
• One Health Setting:

  Human Health Animal Health (including wild-life, livestock, fishes, and companion animals)

• Type of studies/experimental approaches:

  in silico, in vitro, in vivo preclinical and clinical studies in human and in all veterinary settings studies in crop/plant settings, including field studies

• Keywords:

  Resistance breakers; mutation inhibition; in vivo models; structure-guided drug design; medicinal chemistry

• Brief description of your expertise / expertise you are looking for:

  We are a chemical biology and medicinal chemistry laboratory, interested in developing novel methods and new compounds to combat the challenges of AMR through interdisciplinary research. Our lab is based in the Department of Pharmacology, University of Oxford (top of QS world rankings since 2019) and we work with various leading drug discovery centres such as the Oxford Centre for Medicine Discovery and the Ineos Oxford Institute for antimicrobial research. We are looking for collaborators with expertise in: - Structural biology of enzyme-inhibitor complexes to guide design - Testing of synthesised compounds in the context of infection models (e.g. mouse models) - Studies of antibiotic persistence in field/waste water settings

• Brief description of your project / the project you would like to join:

  We have previously identified resistance-breaking compounds that increase bacterial susceptibility to antibiotic classes, including in clinical strains where resistance already exists. Importantly, these compounds function at nanomolar concentrations in cells, and are also capable of inhibiting bacterial responses that drive mutation and persistence. We are therefore seeking collaborators to help translate these promising molecules into in vivo models to demonstrate proof-of-principal clearance of resistant infections. This will require collaborators with expertise in: - Structural biology (Xray/CryoEM) of enzyme-inhibitor complexes, in order to guide design of molecules which will be synthesised in our laboratory. We have already established robust synthetic routes to target molecules. - Testing of synthesised compounds in the context of infection models (e.g. mouse models). We have already established partners to perform metabolic and pharmacokinetic studies that will allow us to develop tool compounds for in vivo studies. - Studies of antibiotic persistence in field/waste water settings, in order to investigate the persistence of compounds in the environment and effects of inhibition of mutagenic responses on environmental selection pressures. It is hoped that these collaborations will also form the basis of future partnerships to develop new and novel ideas to combat AMR.

Thomas Lanyon-Hogg

• Organisation: University of Oxford
• Position: Principal Investigator
• E-mail: thomas.lanyon-hogg@pharm.ox.ac.uk
• Phone: 01865271593
• Web: www.pharm.ox.ac.uk/research/lanyon-hogg-group