Difference between revisions of "Team:ETH Zurich/Human Practices"
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IBD is very complex class of diseases and given that some bacterial species might worsen the condition for patients, it is of the utmost importance to take the necessary precautions to make our bacteria interact as little as possible with the disease. In the following paragraphs we will summarize the interview with Prof. Rogler, where we address these issues. | IBD is very complex class of diseases and given that some bacterial species might worsen the condition for patients, it is of the utmost importance to take the necessary precautions to make our bacteria interact as little as possible with the disease. In the following paragraphs we will summarize the interview with Prof. Rogler, where we address these issues. | ||
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Our project is currently implemented in E. coli, however E. coli lipopolysaccharides are known to increase the immune reaction in IBD patients and are sometimes even connected to pathogenesis. One strain of E. coli, E. coli Nissle, is currently being used as a probiotic in IBD patients and does not increase inflammation. The problem with E. coli Nissle is that it cannot take up any plasmids and it is therefore not a feasible candidate host for our project. | Our project is currently implemented in E. coli, however E. coli lipopolysaccharides are known to increase the immune reaction in IBD patients and are sometimes even connected to pathogenesis. One strain of E. coli, E. coli Nissle, is currently being used as a probiotic in IBD patients and does not increase inflammation. The problem with E. coli Nissle is that it cannot take up any plasmids and it is therefore not a feasible candidate host for our project. | ||
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Revision as of 00:17, 3 December 2016
Human Practices
Overview
Proper communication has been a cornerstone of the scientific method since its birth. From the first letter on his heliocentric model of the solar system that Copernicus dedicated to Pope Paul III, the target was clear: Communicating your findings and educating people on them is key to make science work.
We therefore dedicated our human practices on education and communication, on different levels of the population:
- The general public, through our questionnaire on the streets
- People interested in science, through our participation in the Basel Science Slam
- Reaching a regional audience, through the publication of two newspaper articles
- Discussed how we could affect education on a global level, through the ideas developed at an SDG workshop
Additionally to eductating other people, we sat down with three experts that helped us understand IBD better, define new goals for our project and design an alternative circuits.
Public study on IBD, synthetic biology and ethical issues
Synthetic biology still remains cryptic to the general public who often has a negative opinion on GMOs. Our goal was to inform people about scientific progress, and sensitize them to IBD. Therefore, we designed a questionnaire that would allow us to see how informed the general public is about IBD and educate them on the main issues with IBD, such as the increasing incidence rate in western Nations and the lower life expectancy of the people affected. Additionally, we wanted to educate the public on what is known about the general role of the gut microbiome and how it affects the disease.
We then moved on to tell them about our project and how we want to develop an investigation tool for the disease. This does not come without ethical baggage, therefore we asked people whether it is acceptable to use genetically modified bacteria inside humans for investigating diseases.
Moreover, we tried to convey that biologists are doing everything to keep genetically engineered bacteria from being released into the environment and provide them with an ecological disadvantage. Nevertheless, such a release might be inevitable. How does this information change their opinion on the use of genetically engineered bacteria?
In the Netherlands in 2006, genetically engineered bacteria have been administered to humans in clinical trials to treat IBD[2]. The bacteria had only minor adverse effects on the patients and no environmental hazard was identified. Does this new information change their opinion?
Science Slam Basel
The annual Basel “Science Slam” is an event where the scientists of Basel present topics related to science in an entertaining way in front of a non-expert audience. The point of a “Science Slam” is to bring problems in science closer to the general public. It provides a novel and entertaining way to educate people on certain fields of science. This year, 350 people were in the audience.
We have participated in the 2016 finals, where we presented the topic of scientific misconduct and how projects like iGEM can be taken as an example of how the scientific community can reduce the incidence of scientific misconduct.
Watch Lucas' talk here!
Newspaper article in Corriere Del Ticino
During the summer we collaborated with the main newspaper in the Italian speaking part of Switzerland, Corriere Del Ticino, in the preparation of an article about synthetic biology and iGEM. The two-page article is based on an interview of our team member Mattia Gollub and explains in a comprehensive way what synthetic biology is, the mission of iGEM and the idea of our project. In addition, it presents the main fields where synthetic biology is already used in practical applications. The article also includes an evaluation by the Swiss National Advisory Commission on Biomedical Ethics on synthetic biology projects. In general, we tried to explain synthetic biology in a simple way and demystify prejudices, bringing people closer to the field.
A digital version of the article (in Italian) is available here. Author: Carlo Silini, Correiere Del Ticino, 24.09.2016
Newspaper article in ETH Globe
ETH Globe is the international magazine of ETH Zurich, the target audience of which is ETH Alumni, partner universities and scientifically interested audiences. From the beginning of our project a journalist from ETH Globe has visited us to report on iGEM and the process we are going through. He visited us just before the wiki freeze and will join us at jamboree to convey the relaxed start of the summer until the stressful final days. The article will be published in the December issue of the magazine. You can download the December 2016 edition of ETH Globe here .
Youth rep workshop on United Nations SDGs
The Sustainable Development Goals (SDGs) are projects created by the United Nations Development Program (UNDP) and comprises a call to action to achieve 17 goals by 2030 ( SDG Website ). These goals can be achieved by governments, the private sector, the civil sector or individual citizens and will be funded by the UNDP.
On 17th September the UN youth representatives of Switzerland have organized a workshop with various youth organizations of Switzerland, including Zurich Model United Nations (MUN), Young European Swiss (YES), Youth Party representatives, iGEM ETH Zurich and many more. The goal was to present the SDGs, listen speakers of current SDG related projects already started in Europe. Afterwards, teams were created to determine how our organization can work with other youth representatives to achieve these goals.
It quickly became apparent that iGEM and the different projects it has spawned since its creation have the potential to help achieve multiple goals:
- Goal 1: No Hunger
- Goal 3: Good Health
- Goal 4: Quality Education
- Goal 5: Clean Water and Sanitation
- Goal 7: Renewable energy
- Goal 9: Innovation and Infrastructure
- Goal 14: Life on Land
The competition itself touches on the “Quality Education” goal with its Human Practices component. Our Pavlov’s Coli project and other diagnostics/therapeutics track projects attempt to achieve goal 3. In general, iGEM can show great synergy with the SDGs and we strongly encourage future iGEM teams to collaborate with recognized NGOs (Non-Governmental Organizations) related to achieve SDGs.
Additionally, we collaborated with Zurich MUN and the YES to focus together on goal 4 (Quality Education) and 17 (Partnership for the Goals). Our plan is to organize an event with the motto “Inform, Motivate, Engage!” Given that our common interests are educating people on our subjects, we want to get more people engaged in their subjects. To achieve this we would introduce them to three levels of engagement: Global, Regional and Local.
These also represent the levels at which our projects act: MUN is engaged globally, YES on the European regional level and iGEM teams through their human practices act on a local level.
The event would start by informing how a problem in synthetic biology (e.g. safety issues) can propagate on all three levels of engagement. Then we would try to motivate interested audience members in a workshop to come up with their own ideas how to tackle such problems. The final goal is to get them engaged in youth organizations that start the cycle anew: inform an audience on their subject, motivate interested audience members and help them get engaged in youth organizations.
The plan for such an event has been set, however we were unfortunately not able to find an available date to organize the event before the start of the Jamboree. Nevertheless, it shows iGEM and collaborations with other youth organizations show great potential to achieve SDGs!
The Experts
The field of inflammatory bowel disease (IBD) research partially lacks answers to the most basic questions on microbiome dysbiosis. However, most experts agree that dysbiosis is integral to the pathogenesis of IBD.[1]
In order to address the right problems in our project, we met a number of experts, with whom we discussed not only technical details, but also ethical and safety issues of the project:
- Prof. Gerhard Rogler, Gastroenterologist and expert on IBD at Universitätsspital Zurich
- Prof. Christophe Lacroix, Expert on bacterial metabolites and its role with probiotic bacteria at ETH
- Prof. Martin Jinek, Expert on CRISPR related protein-RNA interactions at University of Zurich
Prof. Gerhard Rogler
IBD is very complex class of diseases and given that some bacterial species might worsen the condition for patients, it is of the utmost importance to take the necessary precautions to make our bacteria interact as little as possible with the disease. In the following paragraphs we will summarize the interview with Prof. Rogler, where we address these issues.
Our project is currently implemented in E. coli, however E. coli lipopolysaccharides are known to increase the immune reaction in IBD patients and are sometimes even connected to pathogenesis. One strain of E. coli, E. coli Nissle, is currently being used as a probiotic in IBD patients and does not increase inflammation. The problem with E. coli Nissle is that it cannot take up any plasmids and it is therefore not a feasible candidate host for our project.
Prof. Rogler therefore suggests using Lactobacillus or Lactococcus lactis as hosts. These genera are not known to increase immune response. The former are already being used as probiotics in IBD patiens and the latter have been used in clinical trials with only minor adverse effects.[2]
On the topic of current methods to investigate microbiome composition, Prof. Rogler stated that tissue samples are taken during endoscopy. Through 16S RNA sequencing the distribution of bacterial populations can be asserted on the phylum level and in some cases even species level. However, such an analysis cannot discern between bacteria that are present and functional and those that are non-functional. A dysbiosis is found in all cases.
Our analysis with nitric oxide (NO) and N-acyl homoserine lactone (AHL) might be a useful tool to investigate simultaneously the state of inflammation and microbiome composition, yet it all depends on the sensitivity of the system. Currently, inflammation is measured through calprotectin levels in the feces of patients; one would have to compare the calprotectin analysis to the measurement of NO in order to assert its effectiveness.
Finally, in order to make the project clinically feasible, we would need to encapsulate our bacteria. There are certain properties in the pill that we need to look out for to make it safe for administration. The material needs to withstand, even partial, digestion by stomach acid and pancreas enzymes. The bacteria need to be prevented from migrating out of the pill and colonizing the gut. Although, the colonization itself is not a safety issue, as a clinical study of L. lactis showed[2], it is certainly not a desirable trait.
Prof. Christophe Lacroix
Our project relies heavily on the sensing of bacterial signaling molecules and metabolites in order to draw conclusions on the factors that affect IBD. Prof. Lacroix was able to point us to interesting markers that our system could sense, in order to determine what role they play in IBD.
The first suggestion he made in order to improve our system was to introduce a health marker that could be replaced with the inflammation marker nitric oxide (NO). This will be useful once we want to compare healthy individuals with IBD patients, in order to establish the difference between the two states. His suggestion was to use butyrate as this candidate marker, as it is a metabolite whose concentration is reduced significantly during IBD.
The most interesting suggestion was that of sensing metabolic intermediates, such as lactate. These will give our project a significant advantage to fecal analysis, as these intermediates will not be present in the feces. Nevertheless, they will allow us to paint the profile of, for example, lactate metabolizing bacteria and determine their dysbiotic behavior in IBD.
In order to make our project feasible, we would need to make sure that our encapsulated bacteria stay close to the mucus, where NO is produced. This will probably be necessary due to NO being relatively short lived.
Prof. Lacroix was also kind enough to offer us access to his gut simulator, a machine imitating the mucus of the gut, on which we could test our system and to their IBD affected mice, in case we would arrive that far in the project.
Prof. Martin Jinek
CRISPR/Cas9 technology has resonated widely within the scientific community and even in the general public. Given the flexibility of the technology, we wanted to design an alternative switch for our system using CRISPR. Given that Prof. Jinek’s 2012 paper[3] introduced the scientific community to this technology, we could not think of a better expert to help us design our switch.
Prof. Jinek introduced us to a new enzyme that his group is investigating and that has been discovered by the Zhang lab at MIT, called Cpf1 [4]. For more details please see our description page.
