Reference number : GC-2017-Q3-00413, amendment number : , agreement type : G, recipient legal name : Gray, Christopher (University of Guelph), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Collaborative Research and Development Grants - Project, program name french : Subventions de recherche et développement coopérative - projet, program purpose english : With development of antibacterial resistance among numerous strains of infectious bacteria, antimicrobial peptides (AMPs) are considered to be among the best candidates to replace traditional antibiotics. AMPs are produced and employed by immune system of most organisms._x000D_
Most of the naturally occurring AMPs are active against several types of infectious bacteria, but many of them are toxic to mammalians at therapeutic dosages. Use of machine learning (ML) methods, together with our current knowledge of natural AMPs, we can discover novel AMPs, with much less toxicity to mammalians and increased effectiveness against pathogens._x000D_
In this project, we will use ML to develop novel AMPs, specifically for targeting the intestinal salmonella infections in pig farms. Data from previously known and studied AMPs will be used as input to the ML calculations. Within a projected two-year period for this project, we expect to deliver better antimicrobials for treating intestinal salmonella infections in pigs. AMPs discovered using ML methods will be tested in vitro for their antimicrobial activity and cytotoxicity. The secondary structure of the best candidate AMPs from this stage will be determined using nuclear magnetic resonance spectroscopy and used in atomistic molecular dynamics simulations to obtain a detailed picture of antimicrobial activity._x000D_
We will examine our best candidate AMP (currently, HHC-36) for its effectiveness and resistance to proteolytic degradation through a number of in vitro tests._x000D_
When administered orally to the infected animal, we require that the peptide resists to degradation by the digestive enzymes and the highly acidic environment of the stomach. We will therefore study the survival rate of the peptide as it passes through simulated intestinal track of the swine. If needed, delivery methods such as use of capsules for preserving the peptide in the pig's digestive system will also be considered and proposed for future animal trials._x000D_, program purpose french : With development of antibacterial resistance among numerous strains of infectious bacteria, antimicrobial peptides (AMPs) are considered to be among the best candidates to replace traditional antibiotics. AMPs are produced and employed by immune system of most organisms._x000D_
Most of the naturally occurring AMPs are active against several types of infectious bacteria, but many of them are toxic to mammalians at therapeutic dosages. Use of machine learning (ML) methods, together with our current knowledge of natural AMPs, we can discover novel AMPs, with much less toxicity to mammalians and increased effectiveness against pathogens._x000D_
In this project, we will use ML to develop novel AMPs, specifically for targeting the intestinal salmonella infections in pig farms. Data from previously known and studied AMPs will be used as input to the ML calculations. Within a projected two-year period for this project, we expect to deliver better antimicrobials for treating intestinal salmonella infections in pigs. AMPs discovered using ML methods will be tested in vitro for their antimicrobial activity and cytotoxicity. The secondary structure of the best candidate AMPs from this stage will be determined using nuclear magnetic resonance spectroscopy and used in atomistic molecular dynamics simulations to obtain a detailed picture of antimicrobial activity._x000D_
We will examine our best candidate AMP (currently, HHC-36) for its effectiveness and resistance to proteolytic degradation through a number of in vitro tests._x000D_
When administered orally to the infected animal, we require that the peptide resists to degradation by the digestive enzymes and the highly acidic environment of the stomach. We will therefore study the survival rate of the peptide as it passes through simulated intestinal track of the swine. If needed, delivery methods such as use of capsules for preserving the peptide in the pig's digestive system will also be considered and proposed for future animal trials._x000D_, agreement title english : Novel antimicrobials for swine health, agreement title french : Novel antimicrobials for swine health, agreement number : CRDPJ, agreement value : 40000.0, agreement start date : 2017-12-13, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year (2017-2018 to 2019-2020)., additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier (2017-2018 à 2019-2020)., owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada