Team:TecMonterrey GDL/Human Practices
Diabetes has evolved from being an unusual disease to a frequent word in our vocabulary. It has become a major problem worldwide and it is particularly alarming in our country, due to the lack of information and the unhealthy and inactive lifestyle of the average Mexican. According to the World Health Organization, during 2016, 10.4% of the Mexican population had diabetes, and this number is expected to increase. What makes this even worse is the socioeconomic current situation of the Mexican population, making the treatment unavailable for everyone. New solutions for prevention, diagnosis, and treatment of diabetes are a priority for science and technology in our country.
This inspired us to create Gliksys, an innovative non-invasive approach for glucose monitoring, easy to use and accessible for everyone.
Objectives
Objective 1
Engage with our community.
Objective 2
Encourage a healthy lifestyle and eating habits.
Objective 3
Inform about diabetes and how to prevent it.
Objective 4
Promote SynBio power!
As we mentioned, for us it is really important to share what we have learned to our local community. We are committed to sensitize our community to raise awareness about chronic-degenerative diseases, such as diabetes. That is the main goal of our social activities: to inform and prevent.
A series of conferences were prepared for college students and professors (academic community), where it was spoken about high-impact researches in chronic-degenerative diseases, the development of biomarkers and the prevention of these diseases through a healthy diet. We also took advantage to present our project to the audience.
More than a hundred spectators attended to the event, including students from different institutions, professors and experienced researchers. The audience shown to be interested in these topics, inquiring about modern biomarkers and the relation between diet and our health.
We made a contribution in a popular science magazine which has a national impact in Mexico, called Más Ciencia por México. The article addresses the dilemma of diabetes in Mexico, focusing on how science can contribute to the development of brand-new technologies, what is genetic engineering and how anyone can be capable of applying their science knowledge in order to make a change in our community. The article was published on the magazine’s main page and shared through social media!
Therefore, we are hoping that divulgation through virtual means generates a positive impact in every citizen of our country, including children, teenagers and adults.
We think is important people know about SynBio. Our school organized a fair where student groups were able to present their projects to the students' community and we saw the opportunity to invite new generations to join us for future iGEM editions. We were able to talk to several peers, including new biotechnology students who didn’t know about iGEM but showed great interest in synthetic biology anyway.
In these activities, we talked about the importance of good nutrition and physical activity among children, through a collaboration with the CFE (Federal Electric Comision). We shared information about diabetes prevention, orienting kids in how people acquire the disease and how we can prevent it with sport and a healthy nutrition. During this workshop, the kids carried out several activities like identifying which foods and drinks were more beneficial for their health. They also performed different activities to illustrate that doing exercise can be both healthy and fun.
Parents' influence in their kids is crucial for their wellness. Even if a kid knows how to eat well, children are going to eat what their parents give them. Because of this, we decided to enhance parents knowledge on how to nourish their children. We collaborated with a community center called “La Colmena”, that seeks to share free activities for kids in order to prevent them from entering possible harmful activities. They allowed us to interact with a group of moms from San Juan de Ocotán, Zapopan (which is considered a vulnerable zone). With the help of a group of nutrition students, moms and others assistants were able to enjoy the activities in which they enhanced their knowledge on a healthy nutrition for kids, which still can be achieved seeing for the family’s economy. Several questions were answered and a debate was performed at the end regarding the daily food given to their kids.
Our project’s success does not only depend on how well we perform inside the lab but also outside. To make sure Gliksys will have a positive impact on society, it was necessary to understand what really happens in terms of the perception of food consumption and the possible diseases of not taking it with responsibility in our community. So we gathered valuable feedback (through iGEM established methodologies) from different sources: people with diabetes, specialized doctors and scientific researchers, so we could align our vision to the real-world necessities of our community.
We initially had an idea of how we wanted to help people with our bioink. However, we realized that what we imagine could work may be different than the actual necessities of potential users: people with diabetes. So we thought the best way to assure our project was beneficial for people was asking them, we also went ahead and decided to ask health specialists, because they are the ones that interact the most with diabetic patients.
To achieve that, we decide to use the Kano model, which was proposed by Valencia’s Team iGEM 2018, a tool to get feedback to adjust the vision of our project to the needs of people living with diabetes in Mexico. We inquired from people with diabetes and medical experts, through the categorization of needs obtained from a paired questions methodology. This is how the bioink research and development was enhanced to accommodate the needs of potential users.
We implemented the Kano model in four stages:
1
Identify your target audience:
We decided to apply this model and get feedback from people with diabetes to know what would they need for our bioink to be a reliable method for glucose monitoring and health specialists, who are the ones that know best what patients with diabetes require.
2
Generate a ‘paired questionnaire’:
We generated paired questions, that is the same question expressed both positively and negatively, each one representing a specific necessity. These will allow us to identify which characteristics of the bioink are the ones we should pay more attention to. Two different sets of paired questions (people with diabetes/health experts) were designed and applied to at least 30 individuals as suggested by Valencia’s Team iGEM methodology.
3
Categorize the opinions:
We classified all the feedback and opinions received into specific categories, to establish the characteristics that should be implemented.
4
Decide what to implement:
Once we had the results of the model, we chose which characteristics are more important and implemented them in the project development and into further considerations.
What we learned and how we used it:
- A quantitative and reliable measurement is necessary, and not only a binary measurement as we initially thought.
- No need for refrigeration and a long duration are important for the users.
- According to our social context, the community needs an affordable and accessible product.
- The product can be presented like a tattoo or a marker.
- The product should be easily found in pharmacies.
Once we gathered the opinion from the final users, we wanted to receive feedback on our proposed molecular mechanism to identify other factors that could influence our final product design. In this way, we consulted researchers that currently work with biomarkers, bioelectronics and bioengineering.
Dr. Enrique Jaime Herrera López
Dr. Enrique Jaime Herrera López is a Senior Researcher B in CIATEJ Industrial Biotechnology Unit Zapopan and is specialized in Bioelectronics.
What we learned and how we used it:
- A way to obtain quantitative information on glucose levels could be by taking a photo of the tattoo, and using a glucose value can be assigned proportionally to the intensity on software programmed with a color scale.
- The disadvantages of our project would be the duration of the skin patch, bioink conservation methods, and the fact that a complementary device is necessary for quantitative measurement.
- The importance to check the safety of the measurement of glucose levels because they are not constant.
Dr. Luis Joel Figueroa Yáñez
Dr. Luis Figueroa is a Principal Researcher in CIATEJ Industrial Biotechnology Unit Zapopan with an expertise in synthetic biology and biosensors. He is currently working with Wet/Dry tools for the analysis, assembly, and edition of genomes through the use of CRISPR-Cas9 in cells of plants, animals and yeast, with the objective of redesigning or creating new biological systems for their application in various industries.
Conclusions from the activity:
- For the glucose levels to be measured by a device we should implement a hybrid system that links the protein production levels and an electric signal..
- To make the measurement more specific for glucose levels try to include the sensing of a metabolite.
- There are three elements to take into consideration if we were to develop a measuring device: the sensor, a biochemical test and how to translate the signal.
Dr. Pavel Hayl Lugo Fabres
Dr. Pavel Hayl Lugo Fabres is a researcher at CIATEJ Medical and pharmaceutical biotechnology Unit Guadalajara. He has a master’s degree in Marine Biotechnology Oriented Sciences and a doctorate in Sciences specializing in Marine Biotechnology. He has a worked in human tuberculosis diagnosis using biomarkers.
Conclusions from the activity:
- The microorganism used must be GRAS (safe) by the FDA, or by the EMA in Europe, and should not represent a problem to a person’s health.
- The patch has to have a substrate metabolized by the microorganism capable of keeping it alive, but that is not enough for it to divide and not proliferate beyond what you need.
- The advantage of bacteria is that they are easily accessible, low cost and ease of maintenance.
- We could use antibodies fixed on vitreous carbon, graphene or silicon to link measurements to an electronic device.
Expert feedback
Up to this point in the course of the project, we had a more clear panorama of the best way of making a bioink that fits the users needs taking into consideration their medical condition. We think that prevention is the clue before we even need to treat a disease. That is why our next goal was to reach our local community to inform them about diabetes and inform how to prevent it. For this, we needed first to understand this topic completely. Part of our research labor included reaching out to experts in the field who can help us improve our understanding of diabetes, what are the factors implicated in its development and how we can prevent it.
Dr. Sergio Sánchez Enríquez
Dr. Sergio Sánchez Enríquez is a Mexican physician, specialized in orthopedic and traumatology. He has a Ph.D. in molecular biology awarded by the University of Guadalajara. He is currently working on metabolic diseases and diabetes.
What we learned and how we used it:
- Non-invasive technologies for the diagnosis of diabetes, such as biomarkers, are becoming a trend because they are comfortable for the patient.
- Qualitative indicators, like color shifting, are more significant for the patient because the user can evaluate the behavior of his/her disease.
- To generate an improved product, you must analyze how you can differentiate yourself from what already exists. A complete glucose detector must combine the originality of synthetic biology (biomolecular mechanisms) and the advantages of chemistry.
- Although there are many instruments used to check your glucose levels, the majority of them vary in their measurements because they do not consider external factors such as the patient's condition.
Dr. Sergio R. Gutierrez Ureña
Dr. Sergio R. Gutierrez Ureña is a physician with a specialty in rheumatology. He is currently the head of the Rheumatology Service from the Guadalajara Civil Hospital Fray Antonio Alcalde.
Conclusions from the activity:
- The bioink is a great idea as it is less invasive and inexpensive but it must be validated. People with diabetes would use it if it is low cost and has minimal variation.
- The bioink must be specific and give a positive and negative predictive value.
- Biomarkers should be clear enough so they can define whether there is or not a particular problem.
Dr. Daniela Gordillo Bastidas
Dr. Daniela Gordillo Bastidas is a Mexican nutritionist. She has a master’s degree and a PhD. in Sciences in Molecular Biology in Medicine awarded by the University of Guadalajara. She is currently working on molecular nutrition and smart food design.
Conclusions from the activity:
- Given that diabetes is a multifactorial disease, not only genetics but also food intake, physical activity and emotions are crucial.
- To develop a distinguished bioink, it has to be sensible but specific for the patient.
- If our device is not able to measure capillary glucose, it will not be useful.
- The perfect device for glucose measuring has to be easy to use.
- Several patients are ranging from 50 to 70 years of age. Complexity may result in accidents with your device.
1
"A more quantitative approach"
At first, we thought the method for measuring glucose should be a simple binary “yes” or “no” qualitative detection. Later when the main user’s, experts, and researchers gave us their feedback, they said that a quantitative approach was better so that it had a more clinical relevance. Based on this we decided to think of a strategy that would allow us to detect glucose concentration gradients (quantitative method) instead of just presence or absence (qualitative method). We selected two promoters that are inducible by analyte concentration, a promoter that is sensitive to changes in arabinose and a promoter for osmolarity, the higher the inducer concentration, the greater the signal (characterization of our promoters), and that increase is proportional and highly specific. This way, we can turn the project into a more quantitative measuring non-invasive method, since this allows us to detect several concentrations of glucose through the intensity of the signal. In our case, we demonstrated this using fluorescence which is related to the final pigment.
2
"The cell is the computer!"
The cell is our computer, so in comparison to other non-invasive glucose measuring devices we don’t need to attach any additional computer instrumentation to sense our signal of interest. The cell does all that by receiving a stimulus through the genetic circuit that we designed, which produces the signal. In this way, we are coupling the detection of an analyte (glucose) through a genetic circuit to the generation of a signal that can be read without the need for additional hardware.
3
"It’s not only a one-way solution"
We designed this biomolecular mechanism to sense glucose levels, having the scope of being of use to people with diabetes and anyone that wants to monitor their levels of glucose in a non-invasive way. Although this mechanism was applied to help people with diabetes, an advantage of using microorganisms is that we can combine different strains to measure and monitor other biomolecules. This approach could help monitor and prevent other types of chronic degenerative diseases. This is the proof of concept, but in reality the biosensor would be composed of more than one type of bacteria. Some these bacteria would work as the sensor but there would be others that could produce quorum peptides that keep the microorganisms viable for a long period of time.
4
"No direct contact with people"
Because GMO’s still face a lot of controversies, our project will incorporate the microorganisms in a matrix so that they are not directly in contact with the skin. This matrix serves to immobilize them at one point, to control their growth, and to immobilize them in a defined geometry. In this way, the matrix will be adhesive to the skin and also, the same matrix nourishes the microorganisms, increasing the viability of the sensor.
