Team:Lambert GA/Human Practices
The LABYRINTH mind map demonstrates the exchange of information throughout the development of the project.
OVERVIEW
This year, our team has been fortunate to continue building our relationship with Dr. Mark Styczynski. During our 2018 iGEM project CAPTIVATE we developed a colorimetric software app. The Stycynski Lab has designed and published articles on zinc biosensors. During discussions, Dr. Styczysnki approached our team to write a colorimetric detection app for their zinc biosensor. The resulting app Zin-Q is the result of this collaboration. As Zinc deficiency is associated with helminthiasis the Zinc biosensor and corresponding app can be an in-field screening device for undiagnosed helminth infections.
Similarly, we continued to work closely with Dr. Saad Bhamla as he provided invaluable mentorship and access to lab equipment. We were also able to engage in a cooperative exchange of feedback and criticism with his research students during collaborative work sessions with his lab team.
Dr. Sammy Bell was our point of contact for the implementation of protocols with regard to industry standards. He also gave us access to other professionals in the field such as Dr. Christian Epe, Dr. David Lowery and Dr. Marcus Terneus who consulted us on project design and implementation. They specifically helped us to refine our target species to C. elegans as a model organism.
Dr. Dana Barr, PI of the Barr-Ryan lab at Emory University was instrumental in gaining access to test the MeshMax prototypes with fecal samples. She also gave feedback on the sensitivity and specificity needs of public health implementation.
iGEM at Georgia State University played an instrumental role as beta testers for our bead homogenizer. They were able to provide constructive feedback related to tunability as well as meaningful discussion and data confirming our homogenizer successfully lysed cells while keeping DNA intact while the commercial version they had used previously could not. Furthermore, they granted us access to their fluorometer so that we could conduct a side-by-side analysis and verify functionality. They also hosted a presentation boot camp where we had the opportunity to practice.
We received support from iGEM UGA as they attended our biotech boot camp as guest speakers and iGEM William and Mary as they contributed financially to the Thirst Project.
Lambert iGEM also worked very closely with Rigil-kent A Ballester Wu the director of Community Service Alliance (CSA), a grassroots organization empowering local communities in the Dominican Republic by supporting women and young people in comprehensive education and income-generating activities. Our team was fortunate enough to travel to his community and experience first-hand, with the help of his colleagues Amauri Sosa and Carlos Pion, the challenges many community members face and engage in a dialogue regarding how synthetic biology has the capacity to mitigate many of these problems. Through CSA, we came in contact with Sandra Velez, the principal of Santa Maria del Batay School and engaged in multiple discussions about resource availability and access. Students shared information about local medicine while we installed hygiene stations, presented foldscopes as a cost-effective alternative to more expensive lab equipment and facilitated student and teacher training to build their capacities to execute science-based hygiene lessons.
In our time in the Dominican Republic, we also met with Dr. Rainer Martinez, a medical doctor who provided insight on many local healthcare issues including the high cost of diagnostic healthcare and the problems many people experience with neglected tropical diseases, most notably helminthiasis.
PROBLEM
Dominican Republic
In 2018 and 2019, members and alumni of Lambert iGEM traveled to Hato Mayor, Dominican Republic to install water filtration systems in rural areas. The team was aware that the Dominican Republic faced widespread waterborne disease due to its fragmented public health system; however, the situation became pronounced when we met low-income families without access to healthcare. During the trip, we met with Dr. Rainier Martinez, a local practicing doctor and member of the health ministry. With his support and expertise, we learned that the most critical issues are neglected tropical diseases (NTDs), the most chronic of which include Lymphatic Filariasis, Schistosomiasis, and Soil-transmitted helminths.[1]
Dr. Rainier Martinez explained the public health concerns of the Dominican Republic to the Lambert team.
The prevalence of helminths is attributed to poor sanitation conditions and a lack of access to diagnostics. Current diagnostic methods such as Kato Katz require feces samples to be collected, smeared on a slide, and analyzed through a microscope. This method is problematic as it requires trained laboratory professionals to conduct procedures. Citizens of developing nations often lack access to laboratories that can conduct testing making diagnosis difficult and traveling to clinics is costly due to both transportation and loss of income. The Kato Katz method is also expensive and prone to human-caused errors due to analysis. Without rapid and accessible diagnostics, many individuals choose to live with the disease rather than paying for a diagnosis.[2]
Families told our team about their health concerns.
The stories of Hato Mayor inspired Lambert iGEM to develop a frugal diagnostic tool for helminth infections. Our accessible and effective test may be able to transform these broken health systems, allowing easy and cheap diagnosis, and treatment for disadvantaged communities around the world.
Boehringer Ingelheim
After identifying the problem, our team sought the help of leading professionals in the pharmaceutical industry whose research is to discover treatments for helminths. Boehringer Ingelheim is the 2nd largest animal pharmaceutical company in the world. We received the advice of their leading experts: Dr. Sammy Bell (Head of Formulation Sciences), Dr. Christian Epe (Head of Parasitology Research), Dr. David Lowery (Director of Biotherapeutics Research), and Dr. Marcus Terneus (Principal Scientist). We presented our initial workflows and solutions; Dr. Bell and Dr. Epe guided us on the most feasible approach to address helminth diagnostics. They suggested we focus on specificity, as methods such as Kato-Katz rely on the presence of eggs Egg identification requires trained personnel and expensive equipment. This leads to the overuse of general anthelmintics such as albendazole rather than specific treatments for each type of worms. The overuse of such anthelmintics have led to reports of anthelmintic resistance in mammals such as goats, cattle, and dogs. To prevent concerns of anthelmintic resistance, they suggested that a precise diagnosis of helminths will give doctors confidence to treat patients with species specific treatments. Lastly, we want to thank Dr. Bell, Dr. Epe and for giving us feedback on presentation on how to appeal to a scientific audience.
Dr. Christian Epe is the Head of Parasitology Research at Boehringer Ingelheim.
Dr. Sammy Bell is the Head of Formulation Sciences at Boehringer Ingelheim.
DEVELOPMENT
MeshMax & OpenCell-X
Also from the Georgia Institute of Technology, Dr. Saad Bhamla of the Bhamla Lab heavily influenced the hardware aspects of our project, specifically the creation of our bead homogenizer and filter. He provided significant insight during our brainstorming period and played a major role during development and testing. For our bead homogenizer, Dr. Bhamla helped us realize the issues in our lysing model. Our first homogenizer prototype, LyseX, homogenized cells but did not produce usable DNA. With Dr. Bhamla’s expertise, we switched to a less mechanically invasive model, GearX. The Bhamla Lab generously allowed us to use their SLA printer to create GearX. To test this new model, we also used Dr. Bhamla’s high-speed camera to analyze the motion of beads and determine the centrifugal force. Dr. Bhamla also advised on our filter MeshMax, suggesting we change the size of the channels to hold more eggs. The Bhamla Lab was an integral part in developing our hardware devices and determining the direction of our project as a whole.
Dr. Saad Bhamla is a professor at the Georgia Institute of Technology.
Georgia State University's iGEM team tested OpenCell in their lab to affirm the efficacy and functionality of our frugal device. They applied the bead homogenizing protocol on microalgae, testing one sample using OpenCell and the other using a commercial homogenizer. While the commercial homogenizer was too aggressive for the microalgae, leaving minimal live cells, there were live and motile cells in OpenCell's sample. We greatly appreciate GSU iGEM for testing our device and offering valuable feedback to optimize user interaction.
Toehold Design
Yan Zhang of the Styczinski Research Group at the Georgia Institute of Technology assisted the team in designing our C. elegans proof-of-concept toehold. She provided the team with software code for designing the toehold on the Nupack development suite. Her professional insight was our primary resource for troubleshooting over the course of our wet-lab workflow.
Yan Zhang is a doctoral candidate of the Styczinski Research Group at the Georgia Institute of Technology.
Zin-Q
In the Spring, the Styczinski Research Group reached out to collaborate on developing Zin-Q, a smartphone-based colorimetric test for the quantification of zinc in blood serum. Their lab is researching biosensor detection of Zinc in the field. This collaboration is significant as zinc levels in blood serum are positively correlated to the presence of helminth infection. Zin-Q can be used as prescreening in-field test to determine if an individual shows symptoms of helminth infections before proceeding with our biosensor detection.
Dr. Mark Styczinski is a professor at the Georgia Institute of Technology.
Fluorocents
The Bhamla Lab advised the hardware team on the development of our low-cost fluorometer and corresponding app, Fluorocents. Dr. Bhamla emphasized the importance of having a filter for accurate readings in our device. He also suggested using an Ambient Light Sensor instead of RGB values. While Dr. Bhamla presented important concerns on the scope of our device, he encouraged us to pursue the project, acknowledging its potential for precision and accuracy.
IMPLEMENTATION
Thirst Project
The Thirst Project expands the scope of our project. Throughout the year, iGEM members have been in frequent contact with Evan Wesley, Thirst Project’s Vice President of Student Activation, asking questions, fielding ideas, and underlining the true motivation behind our work. Beyond our project on helminths in feces and soil, millions around the world also contract helminth infections through unsafe drinking water. Evan informed us that through his experiences around the world in areas most affected by these diseases, the most urgent need of health workers and humanitarian volunteers is useful, accessible data. Taking these words to heart, we were inspired to create the frugal devices and software mapping tools that drive our project. Our work with the Thirst Project combined with our trip to the Dominican Republic pushed us to begin our own campaign to help end the global water crisis. We set a goal of raising enough money to build a well in eSwatini. Evan provided insight into our marketing and fundraising efforts. He advised us to reach out through social media to widen our influence and promote the Thirst Project through a challenge to appeal to larger audiences. Lambert iGEM is excited to continue our work with the Thirst Project to help end the global water crisis.
Lambert iGEM raised money to build a well in eSwatini.
Bead Homogenizer Survey
Lambert iGEM conducted a survey among iGEM teams and labs around the world to determine the demand for OpenCell, our low-cost bead homogenizer. Our team found that over 70% of iGEM teams considered themselves underfunded. Less than 30% of respondents had full-time access to a working bead homogenizer. iGEM VIT Vellore spoke to the necessity of our project, saying, “Yes, we do think a frugal bead homogenizer can be beneficial. Research labs in developing countries sometimes are not as efficient as they do not have access to or cannot afford costly equipments. This is therefore, replaced by manual methods to carry out the same task, which in turn, decreases the efficiency. Since your device is more economical, majority or research labs would be able to afford it which would increase the efficiency and output produced by such labs in developing and underdeveloped countries.” These words along with Lambert iGEM’s own experiences as an underfunded lab helped us recognize the necessity of tools such as OpenCell, an alternative to commercial homogenizers and the latest addition to our team’s legacy of frugal lab devices.
Lambert iGEM surveyed other iGEM teams regarding their level of funding and equipment.
The Impact
There is a stark healthcare accessibility gap between developing nations and developed nations. The root of this problem is the cost and infrastructure. However, our team aims to help communities like Hato Mayor by providing inexpensive and affordable alternative for diagnosis. Instead of going to a laboratory to be tested for infections, health workers are now able to conduct tests in local clinics with a faster and cheaper diagnosis. Earlier diagnosis, allows for earlier treatment and a higher quality of life. With a healthier and proactive community, nations like the Dominican Republic are able to focus on their economy, infrastructure, and education.
REFERENCES
[1] Dominican Republic. (2019). Global atlas of helminth infections. London Applied and Spatial Epidemiology Research Group. Retrieved from http://www.thiswormyworld.org/maps/do
[2] Bench Aids for the Diagnosis of Intestinal Parasites. (2012). World Health Organization. Retrieved from https://apps.who.int/iris/handle/10665/37323