Difference between revisions of "Team:Paris Bettencourt/Human Practices"

 
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<h2 id="Introduction">Introduction</h2>
 
<h2 id="Introduction">Introduction</h2>
 
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<p>We are a team of scientists from diverse backgrounds and we started our project with the perspective of a researcher.</br>
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<p>We are a group of diverse talents coming from different fields aiming to solve one of the world’s current challenges through synthetic biology. This year, we are tackling the global threat of <b>antimicrobial resistance</b>. With the increase in the number of multidrug-resistant bacteria, antimicrobial resistance is one of the public health threats we face today.
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We understand the basic concepts behind the evolution of antibiotic resistance. Measures reducing antibiotic use will tend to reduce antibiotic resistance. With this simple understanding, we decided to work on a technology to replace antibiotics.</p>
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<p>We thought that Antimicrobial Peptides (AMPs) were simply cool! They have beautiful peptide structures and can be engineered by interesting methods.</p>
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<p>Our advisors encouraged us to work on AMPs because they are small, easy to design and to test on bacteria - all the prerequisites to simplify an iGEM project.</br></p
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<p>Antibiotic overuse in<b> livestock industry </b>is one of the major drivers to the antibiotic resistance evolution — motivating calls to reduce, replace, and re-think the antibiotic usage in animals. <b>Antimicrobial peptides (AMPs)</b> are a promising alternative to conventional antibiotics. Recently, a class of chemically-synthesized, star-shaped AMPs has been shown to exhibit broad-spectrum antimicrobial activity while maintaining biocompatibility with mammalian cells. 
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<p>These features led us to explore applications of AMPs as replacement antibiotics.</p><p>But what type of AMPs?</p>
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<p>What antibiotics do we need to replace?</p>
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<p> As we design our work in constructing <b>StarCores</b>, we stumbled upon essential questions such as, what type of AMP to use that will yield into a stable protein structure conformation? More importantly, what antibiotics do we need to replace, particularly in the livestock industry? In order to narrow down our broad concept, we did literature search and reached out to the people who are involved in this line of work such as veterinarians and farmers.</p>
 
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<p>Instead of blindly designing AMPs to kill any bacteria, we tried to make sure that we would produce something useful in the real world. That means going outside the lab to meet with the real people who combat antibiotic resistance in the places where they work.</p>
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<p>Without further ado, the <b>integrated human practice section</b> tells the  wonderful story of how we went from simple, monomeric AMPs into a  nontoxic, multimeric StarCores aiming to treat gastrointestinal infection in piglet caused by Gram-negative bacteria.</p>
 
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<p>The Integrated Design section tells the story of how we went from “AMPs are cool” to a concrete project developing specific, nontoxic AMPs to treat Gram-negative infections in the piglet gut.</p>
 
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<h3>France has a robust policy to reduce antibiotic resistance</h3>
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<h3><b>France has a robust policy to reduce antibiotic resistance</b></h3>
 
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<p>Beginning in 2001, France has implemented a series of policies to combat the rise of antibiotic resistance. The overall goals could be summarized:</p>
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<p>Since 2001, France has implemented a series of policies to combat the rise of antibiotic resistance. The overall goals could be summarized as follows:</p>
 
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<h3>Veterinarians confront antibiotic resistance in pigs</h3>
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<h3>The importance of E. coli and other Gram-negatives</h3>
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<h3><b>The importance of <i>E. coli</i> and other Gram-negatives</b></h3>
 
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<p>Once we had decided to focus on pig intestine infections,  we wanted more specific data about the pathogens and resistances at work. We attended the conference “Antimicrobial Resistance and Society” at the Institut Curie. There we met Jean-Yves Madec, scientific director of ANSES, the national food security agency. He confirmed for us that piglet gut infections are a major concern and that E. coli and other Gram-negative pathogens are the most common cause.</p>
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<p>Once we had decided to focus on pig intestine infections,  we wanted more specific data about the pathogens and resistances at work. We attended the conference “Antimicrobial Resistance and Society” at the Institut Curie. There we met Jean-Yves Madec, scientific director of ANSES, the national food security agency.</p>
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<p> He confirmed for us that piglet gut infections are a major concern and that E. coli and other Gram-negative pathogens are the most common cause.</p>
 
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<h3>Publishing our Work in The Conversation</h3>
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<p>Our research into the problem of antibiotic resistance brought us into contact with farmers, doctors, researchers and policy professionals all over France. Along the way, we befriended many good people from different domains, united by a common goal. We had even obtained an original, unpublished data set to study and analyze.</br>
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<p>Table 1: <i>E. coli</i> sensitivity to several families of antibiotics from French pigs of farms in Brittany.<i> E. coli</i> appears to be the least sensitive towards Tetracyclin. The colours indicate the types of antibiotics.</p>
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Thinking back to the original policy goals that motivated us, one of them was raising awareness and informing the public. We contacted The Conversation, a news magazine that specializes in making academic research accessible to the public. With help from their journalists and editors, our study of antibiotic resistance in France was published in both French and English.</p>
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<h2>Publishing our Work in The Conversation</h2>
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<p>Our research into the problem of antibiotic resistance brought us into contact with farmers, doctors, researchers and policy professionals all over France. Along the way, we befriended many good people from different domains, united by a common goal. We had even obtained an original, unpublished data set to study and analyze.</br></p>
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<p>Thinking back to the original policy goals that motivated us, one of them was raising awareness and informing the public. We contacted The Conversation, a news magazine that specializes in making academic research accessible to the public. With help from their journalists and editors, our study of antibiotic resistance in France was published in both French and English.</p>
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<p>Article :
 
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<a href="https://2018.igem.org/Team:Paris_Bettencourt/Article">Piglets, bacteria and antibiotic resistance: a dangerous combination for human health</a>
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<a href="https://theconversation.com/porcelet-bacteries-et-antibioresistance-un-trio-dangereux-pour-la-sante-humaine-104723"> Piglets, bacteria and antibiotic resistance: a dangerous combination for human health</a>
 
<a href="https://static.igem.org/mediawiki/2018/6/66/T--Paris_Bettencourt--Article-Piglets-Bacteria-Antibiotic-Resistance-TheConversation.pdf" target="_blank">PDF</a></p>
 
<a href="https://static.igem.org/mediawiki/2018/6/66/T--Paris_Bettencourt--Article-Piglets-Bacteria-Antibiotic-Resistance-TheConversation.pdf" target="_blank">PDF</a></p>
 
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<h2>Integrated Design</h2>  
 
<h2>Integrated Design</h2>  
 
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Latest revision as of 10:51, 10 December 2018

Human Practices - Integrated Design

Introduction




We are a group of diverse talents coming from different fields aiming to solve one of the world’s current challenges through synthetic biology. This year, we are tackling the global threat of antimicrobial resistance. With the increase in the number of multidrug-resistant bacteria, antimicrobial resistance is one of the public health threats we face today.

Antibiotic overuse in livestock industry is one of the major drivers to the antibiotic resistance evolution — motivating calls to reduce, replace, and re-think the antibiotic usage in animals. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics. Recently, a class of chemically-synthesized, star-shaped AMPs has been shown to exhibit broad-spectrum antimicrobial activity while maintaining biocompatibility with mammalian cells. 

As we design our work in constructing StarCores, we stumbled upon essential questions such as, what type of AMP to use that will yield into a stable protein structure conformation? More importantly, what antibiotics do we need to replace, particularly in the livestock industry? In order to narrow down our broad concept, we did literature search and reached out to the people who are involved in this line of work such as veterinarians and farmers.

Without further ado, the integrated human practice section tells the wonderful story of how we went from simple, monomeric AMPs into a nontoxic, multimeric StarCores aiming to treat gastrointestinal infection in piglet caused by Gram-negative bacteria.

Results

France has a robust policy to reduce antibiotic resistance

Since 2001, France has implemented a series of policies to combat the rise of antibiotic resistance. The overall goals could be summarized as follows:

  • To “reduce, replace and re-think” the use of antibiotics in humans and animals.

  • To raise awareness of the problem among doctors, veterinarians and the public.

  • To coordinate policy with other countries under the slogan “One World, One Health.”

    • We studied these policies, using them to frame our own research. From this, we learned about ECOANTIBIO, a national plan created by the Ministry of Health to reduce antibiotic use in livestock by 25% over five years. This program is coordinated with similar efforts to reduce antibiotic use in humans, with the knowledge that antibiotic resistance can pass easily from animal to human pathogens.

    The policy goal to raise awareness was successful in France. Thanks to our study of the existing French policy, we realized that the veterinary sector was a major priority.

    Veterinarians confront antibiotic resistance in pigs

    We reached out to our personal networks to find people on the front lines of antibiotic resistance. We traveled to Brittany, a major center of French meat production, and met with:

  • Marc Quere, a retired veterinarian and writer.

  • Paul Pfister, the CEO of a large veterinary practice.

  • Benoît Quéro, a vet and the mayor of Plumeliau, a farming town.

    • From these veterinarians, we learned of the real-world challenges of treating antibiotics in piglets. Pork represents 46% of the meat consumed in France, making the pig industry a major consumer of antibiotics.

    Piglets in particular are sensitive to digestive disease and easily die from them, so farmers treat infections aggressively. We decided to target piglet intestinal infections for our application.

    The importance of E. coli and other Gram-negatives

    Once we had decided to focus on pig intestine infections, we wanted more specific data about the pathogens and resistances at work. We attended the conference “Antimicrobial Resistance and Society” at the Institut Curie. There we met Jean-Yves Madec, scientific director of ANSES, the national food security agency.

    He confirmed for us that piglet gut infections are a major concern and that E. coli and other Gram-negative pathogens are the most common cause.

    With his help, we obtained access to raw data from PORC 2017, a surveillance program for antibiotic resistance in animals. These data highlight amoxicillin and tetracycline as drugs with the most frequent evolved resistance. With this information, we knew which bacterial species we needed to target and which drugs we needed to replace.

    Table 1: E. coli sensitivity to several families of antibiotics from French pigs of farms in Brittany. E. coli appears to be the least sensitive towards Tetracyclin. The colours indicate the types of antibiotics.

    Publishing our Work in The Conversation

    Our research into the problem of antibiotic resistance brought us into contact with farmers, doctors, researchers and policy professionals all over France. Along the way, we befriended many good people from different domains, united by a common goal. We had even obtained an original, unpublished data set to study and analyze.

    Thinking back to the original policy goals that motivated us, one of them was raising awareness and informing the public. We contacted The Conversation, a news magazine that specializes in making academic research accessible to the public. With help from their journalists and editors, our study of antibiotic resistance in France was published in both French and English.

    Article : Piglets, bacteria and antibiotic resistance: a dangerous combination for human health PDF

    Integrated Design



    Our work in Integrated Design lead us to the key features needed for our antibiotic replacement.

  • An antimicrobial peptide

  • to replace amoxicillin and tetracycline

  • for killing Gram-negative E.coli

  • in the piglet intestine

  • with low toxicity to mammalian cells

    • Centre for Research and Interdisciplinarity (CRI)
    Faculty of Medicine Cochin Port-Royal, South wing, 2nd floor
    Paris Descartes University
    24, rue du Faubourg Saint Jacques
    75014 Paris, France
    paris-bettencourt-2018@cri-paris.org