Team:UFMG Brazil/Synenergene
Project
Lab Work
Modeling
Practices
Synenergene
Team
SYNENERGENE
The team has worked in the project’s Policy & Practices in collaboration with SYNENERGENE, a large European network of partner institutions aiming at Responsible Research and Innovation (RRI) in synthetic biology. A grant-funded collaboration was mediated by Synenergene’s partner, the Rathenau Institut, between UFMG_Brazil team and the University of Bergen.
In the partnership, the hard impacts of the project’s applications have been explored and discussed aiming to develop the Application Scenarios. Using the Application Scenarios, we discussed the soft impacts and therefore investigated the desirability of our application in what was called Techno-moral Scenarios.
What is Synenergene?SYNENERGENE is a four-years mobilization and mutual learning action plan supported by the European Commission under the 7th Framework Programme. The project aims to contribute to Responsible Research and Innovation in synthetic biology by establishing an open dialogue between stakeholders concerning synbio’s potential benefits and risks, and by exploring possibilities for its collaborative shaping on the basis of public participation.
Learn more: Synenergene
What is the Rathenau Instituut?The Rathenau Instituut is a Dutch technology assement center focused on the impacts of Synthetic Biology in society. The Rathenau Instituut studies developments in science and technology, interprets their potential impact on society and policy, and fosters dialogue and debate in support of decision-making on science and technology.
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APPLICATION SCENARIOS
Macrophage-mediated Inflammatory Disorders
Mediators of inflammation induced by macrophages are critical for a variety of human inflammatory disorders (Jou et al., 2013). Our project is on the treatment of joint inflammatory diseases by producing a drug, Interferon beta (IFN-β) which is used to the treatment of Rheumatoid Arthritis (RA) with a modelling system based on the Gout.
Leishmania as a new chassi
Nowadays only a few types of chassis are extremely employed and promoted, as bacteria chassis (Escherichia coli and Bacillus subtilis) and yeast chassis (Saccharomyces cerevisiae). Considering this, there are chassis and bioparts intensively used and developed in detriment of others that can provide a foundation for new applications and benefits when considering cells tropism.
The protozoan Leishmania is a good new chassi candidate. First, because of its ability to infect macrophages (Selvapandiyan et al., 2004). Also, because of its ability to express proteins with proper post-translational modifications and its ability to deliver those proteins inside macrophages. The visceral Leishmania donovani strain with the virulence factor centrin-1 deleted has very low risks of contamination, and its virulence reduction has been evaluated and confirmed with different animal models, such as mice (Selvapandiyan et al., 2006), hamsters (Selvapandiyan et al., 2009), and dogs (Fiuza et al., 2014).
The genetically targeted and defined attenuation reduces the risk of reversionl to virulence, a concern generally raised for attenuated organisms that are created by random genomic mutations. LdCen1 deletion specifically attenuated the amastigote stage of the parasite that replicates inside macrophages, and has no effect on the growth of the promastigote form (Selvapadiyan et al., 2012).
In addition, the team is building a Kill Switch system based on the control of the gene of the enzyme 3'nucleotidase/nuclease, which is crucial for the purine rescuing on the promastigote form of the Leishmania, the one which is spread by the sandflies, aiming to keep the modified parasite from spreading. The enzyme's synthesis would be regulated by a Tetracycline repressor and so the Leishmania would be cultivated in the presence of Tetracycline.
The propose is to use an optimized visceral Leishmania strain to direct IFN-β to specific macrophages associated to joint inflammatory diseases. The team foresees the possibility of turning this idea into a product.
The struggle
In general, society is detached from academia and new approaches developed in research face initial difficulties in being well accepted by general public. One of the UFMG-Brazil iGEM team project’s main challenges is to work with the public acceptance to the use of attenuated pathogens as a disease treatment.
To deal with this issue, the team initially conducted a survey at different points of Belo Horizonte with two main goals: (i) to know how concerned general people would be about the approach proposed by our group; (ii) to inform people about synthetic biology.
Public background and opinion
In order to support the hypothesis of tough acceptance of our project by the general public two surveys would be performed: (i) A quantitative survey (ii) A qualitative survey. Untill the present moment only the quantitative survey was performed. In the survey questions on people’s opinions about genetically modified organisms (GMOs), most respondents (75%) showed that they were familiar with the concept, but the majority is unsure about the benefits they can provide (25.7% thinks they are bad for society and 34.2% do not know what to respond) (see Figure attached).
The two main mistrusts reported by the public were the possibility of something going wrong, leading to the creation of a more dangerous pathogen than the pre-existing one; and the lack of faith that the Leishmania strain is indeed apathogenic. After a brief explanation on the organism’s safety by discussing its disability of causing Leishmaniasis, there was observed an opinion change and people seemed more sympathetic to the idea, leading to a detected 84.5% acceptance to the team’s idea, after considering it as a treatment like any other for a disease.
The reactions detected in the survey’s results made the team realize that there is a lack of information and discussion about genetically modified organisms and synthetic biology between society and scientific community (see figure attached). However, the qualitative survey should be applied in order to understand better why and how interviewees showed a sudden change of opinion after a short explanation on the parasite's safety.
Also, the team wishes to investigate how much the interviewees know about safety on GMOs by asking them what kind of expertise would/should be required for the parasite to be safe enough to medical uses.
