Team:TecMonterrey GDL/Description
What we are facing
Diabetes mellitus remains a leading cause of morbidity and mortality worldwide, which has been aggravated due to a rapidly increasing prevalence in middle- and low-income countries. High blood glucose (hyperglycemia) remains a major concern for diabetic patients since it often leads to severe vascular comorbidities, including retinopathy, nephropathy, neuropathy, and coronary artery disease.
Inspiration
Diabetes is one of the major health challenges we face in Mexico. Our country spends more than 3.4 billion USD each year on diabetes related issues. We looked at how the choice of glucose monitoring method affects the lives of patients living with diabetes. We evaluated novel and conventional approaches, and we realized continuous monitoring systems are optimal to provide information about the effect of various lifestyle choices on the progression of the disease. However, the costs associated with these technologies often restrict their availability in developing countries. Therefore, our goal was to develop a cost-efficient and non-invasive biosensor that could be readily available to the majority of the population in our country. After an extensive literature review, we read about a chimeric receptor that is sensitive to changes in glucose and could trigger gene expression. This receptor had been studied previously in cancer research but held great potential to develop a biosensor for diabetic patients. We believe synthetic biology offers several advantages to approach this type of problematic, as a tool to develop scalable and accessible alternatives to current methods.
Current methods
Continuous glucose monitoring (CGM) has emerged as an effective strategy to help patients achieve and maintain normal glucose levels. However, the implementation of conventional electrochemical biosensors into non-invasive platforms for multiparametric biosensing presents several technical limitations. This is critical since the simultaneous monitoring of physiological parameters (temperature, pH) and diabetes-related biomarkers (glucose, insulin, glucagon) could constitute a more convenient strategy to engineer devices with improved clinical efficacy.
Our proposal
In this regard, whole-cell biosensors (WCBs) hold great potential for the simultaneous monitoring of multiple variables in vivo. This is mainly because of our ability to design genetic circuits that can couple different cellular inputs to the generation of a readily detectable signal. Although microbial WCBs have been widely used for environmental applications, their implementation in precision medicine and wearable/implantable biomedical devices remains largely unexplored.
How would it work?
Previous studies have shown that the efficacy of WCBs can be increased via cellular immobilization or encapsulation, which helps preserve bacteria in an active physiological state. This approach also enables the ability to control the spatial organization of multiple bacterial strains with different biosensing capabilities. We hypothesize that genetically engineered bacteria encapsulated within a polymeric matrix (a bio-ink) can be used to print wearable/implantable WCBs for monitoring and managing diabetic patients. Moreover, this approach could also be explored to engineer implantable devices for controlled release of therapeutic agents such as recombinant insulin produced by encapsulated bacteria. For this, we will use synthetic biology to generate bacteria with different biosensing and reporter capabilities. We will encapsulate different combinations of these bacteria within a polymeric matrix to fabricate different devices, such as epidermal bio-tattoos, microneedles, and implantable scaffolds.
How is it going to help?
We envision that these microfabricated WCBs could be used to engineer wearable/implantable devices for the clinical management of diabetes. Furthermore, the ability of WCBs to transduce biological recognition into a colorimetric signal will allow the design of devices that do not require expensive analytical equipment or trained personnel to be applied and interpreted.
Major risk factors
One of the major risk factors associated with the onset of diabetes is obesity. Although obesity is largely preventable, its worldwide incidence has nearly tripled since 1975 and over 340 million children and adolescents were overweight or obese in 2016. This is a particularly pressing situation in Mexico, since it ranks number one in childhood obesity while also being home to 1.5 million children suffering from chronic malnutrition. Therefore, our human practices strategy will be oriented towards the promotion of proper nutritional habits in children and adolescents in our community. We will organize different strategies to raise awareness and will leverage on our strong background in food science to design activities related to personalized nutrition, and the preparation of functional foods based on different pre- and probiotics, nutraceuticals and bioactive ingredients.
Significance
Owing to the increasing worldwide prevalence of diabetes, novel approaches for CGM that can be readily implemented without the need for trained personnel are highly ideal. Bacterial WCBs capable of simultaneous and continuous monitoring of multiple diabetes-related parameters could be used to engineer devices that can help diabetic patients achieve and maintain normal blood glucose levels. This approach presents several technical advantages over conventional electrochemical biosensors such as multiparametric measurements, autonomy, simplicity, cost-effectiveness, and ease of administration/interpretation. More info: https://www.who.int/news-room/fact-sheets/detail/diabetes
Most of them arise from bad monitoring of an otherwise manageable disease, not only is bad monitoring and issue but many in rural areas people can't rely on insulin pumps and have to constantly and often pinch themselves to take a blood sample and measure its glucose concentration, a process both intrusive and bothersome.
References:
Panteli, J., Forbes, N. 2016. Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cells masses. Biotechnology Bioengineering, 113(11): 2474-2484.
iGEM09_Edinburgh. 2009. Part:BBa_K216004: Trz hybrid signal transduction protein. Retrieved from: http://parts.igem.org/Part:BBa_K216004
