Integrated Human Practices

Local School Visit

Ann Arbor STEAM is a local elementary and middle school with a project-based learning approach which focuses on an integrated curriculum with real-world applications. As a result, the school's mission statement aligns very closely with our team's as well as iGEM's as a whole. We connected with Ms. Jennie Allan, a 7th and 8th grade science teacher, when she was planning the 8th grade genetics unit. Their unit was focusing on the myostatin gene for hypermuscularity in cattle as found in the Belgian Blue breed. After discussion with Ms. Allan on appropriate difficulty level and scientific focus, we organized materials for and taught a class on key concepts used in our project, namely alleles, DNA amplification, platelets, and LAMP in order to highlight the applications of what they were learning. In order to maintain student interest we had an interactive presentation, as well as a worksheet on the concepts we presented on. We specifically designed the worksheet to utilize tangible concepts like dog breed traits, as recommended by Ms. Allan, to help students connect the topics we presented on to other information they have learned in past class sessions.

Lastly, we used a pre and post-survey method in order to gauge how our research was communicated to and understood by the students. The surveys were primarily to gauge how the students' perceptions and understanding changed throughout the course of the lecture. From these surveys, we were pleased to see that students felt they gained understanding in specific topics in genetics from our class session. We also felt the student feedback was valuable in terms of our future educational initiatives.

Here, we have provided blank copies of our surveys for use by other interested parties:

• Pre-Survey
• Post-Survey

SNP Databases

Our SNP Database was partially suggested by Dr. Smith with regards to using our LAMP amplification and fluorescence platform to detect many different SNPs, expanding beyond cardiovascular disease. This discussion with Dr. Smith, along with Dr. Holinstat's research, prompted us to seek to provide a basis for SNP involvement in drug response in our SNP database. Holinstat's research has suggested a link between patient response to standard-of-care antithrombotic drugs and the SNP of interest in our project, rs773902. We wanted to provide a central location for researchers to find the resources they would need for using the platform, such as the wild-type gene sequence, role in drug response, and SNP sequence change. We envision future researchers expanding on the SNP detection method we used in our project for detection of SNPs listed in the database, or applying other methods based on their community needs or expertise.

Discover Engineering Camp

University of Michigan's Discover Engineering Camp is geared towards 8th — 10th grade students who want to thoroughly explore various engineering disciplines. MSBT partnered with the Biomedical Engineering Department to design and run their workshop. The workshop we designed introduced the campers to scientific methods, wet lab work, and the applications of biomedical engineering and synthetic biology. Our workshop had the campers simulate a drug delivery system by creating alginate beads with BSA (a model drug) in calcium chloride, half of which were treated with an acid wash and half that remained the original state. This acid wash increased the bonding throughout the beads and made the BSA diffuse out of the beads at a slower rate. We had the students hypothesize this relationship through graphs as well as predict the outcome of an assay that would show the amount of BSA in solution through a color change.

We were able to share our love of synthetic biology and the many applications beyond the classroom activity, such as MSBT's project and other opportunities at the University of Michigan.

Health Equity Symposium

We strongly feel that medical inequity is an issue that extends even beyond our local community and iGEM project for this year. As a team, we felt it was important to contribute to a growing discussion of research and efforts towards promoting medical equity at both the local and global scales. From our past collaborations with iGEM teams, we know that many teams have shared interests and commitment to bettering their local communities, especially in the topic of medical equity. MSBT decided to host a virtual medical equity symposium for teams to converge and share information about how their projects aim to address specific areas of medical equity while utilizing synthetic biology, as well as host a discussion space where teams could ideate and plan future joint community initiatives. The teams we reached out to that signed up for the symposium were PathoGlow, OASYS, Metriotect, Oxford, Tonji China, William and Mary, and GeneHackers. A recording of the symposium is available on our 'Michigan iGEM' Youtube page.

The symposium yielded great discussion and ideas floating between teams. Attendees expressed their agreement that having a diverse set of projects, from point of care SNP diagnostics, to water quality testing and soil and environmental health, benefitted the perspectives we were able to gain. MSBT learned about how local policies or access to resources greatly impacted the perceived medical equity across regions, and we brainstormed with other teams about various educational and scientific initiatives to promote application of the intersection of synthetic biology and community action. In addition, we also found the symposium as a helpful way to share ideas between teams on the timelines of their human practices initiatives, and what strategies they found to be most impactful. We discussed embarking on collaboration early in the next project season, when project feedback may be most useful, and also discussed plans to make shared resources for human practices, similar to the educational materials prepared by teams in the United Kingdom, as suggested by team Oxford. Overall, we feel that the medical equity symposium succeeded in its goal of promoting dialogue in medical equity research and fostering collaboration amongst iGEM teams.

Collaboration with UChicago iGEM

Our team recognizes that biomedical research is a collaborative endeavor, and that coming together with other research teams can yield valuable new perspectives and opportunities. This year, our team collaborated with the University of Chicago's iGEM team. Together, we forged several collaborative initiatives of mutual benefit.

Through discussing each team's current wet lab struggles and points of need, our collaboration yielded ways in which the other team's access to equipment and/or expertise could aid our projects. Our team was primarily interested in gaining secondary validation of our test's efficacy. Our project's end goal is to develop an end-to-end kit that can be purchased by any healthcare team and used to easily perform our described assay. We planned that UChicago iGEM would serve as a mock end-user; we were to send their team all reagents we anticipate including in our kit along with instructions for use, then having them perform our assay on a test sample. This would enable our team to receive secondary validation that our kit's mechanism is biochemically sound and reproducible, and that our instructions of use are straightforward and easily followed. Due to project setbacks and a lack of assay functionality, this validation step was never performed. However, we feel that this confirmation of results is crucial to the research process, and we hope to implement this kind of validation in future years through continued collaboration with UChicago iGEM.

When discussing the science-related needs of the UChicago team, they highlighted their need to use mass spectrometry to confirm a suspected result of their project. Due to our team's experience with our university's mass spectrometry core facility, we planned for them to send their sample to our university and for our team to run it. This mode of collaboration did not ultimately occur due to setbacks in UChicago's sample production. However, this idea has helped our team recognize that other groups may have access to more specialized equipment or may be more experienced in performing a certain advanced experiment. Therefore, we hope to plan equipment-based collaborations such as this one in the future. Additionally, the UChicago team highlighted their desire to implement machine learning and molecular dynamics into their dry lab work, just as our team has done this season and in past seasons. As such, we planned a follow-up “Computational Modeling” workshop, during which we assisted UChicago team members with dry-lab experimental planning (eg. softwares to use, analyses to run, etc.). Further, we also discussed strategies for teaching computational modeling to new team members, as very few people who enter both teams have prior experience in the area.

In terms of our team's human practices initiatives, we have begun to plan a seminar for next year in which our team members will discuss their experiences studying biology and engineering in college, performing research, and participating in iGEM with local middle and high school students. We aspire for this event to motivate and inspire students in our community to pursue university-level study in these fields, and to perhaps one day pursue careers in synthetic biology. In our collaboration with UChicago iGEM, they have agreed to speak at this event in the capacity of providing additional perspectives on these matters.

Our teams also ideated several long-term initiatives to collaborate on. Between our two groups, we proposed an in-person meetup due to the close proximity of our universities. With each of our groups being focused within the field of synthetic biology, a very niche field in the broader context of our universities, we figured that in-person collaboration would provide the unique opportunity to interact with others interested in this area of research. Additionally, our teams hope to collaborate to establish a stronger community of undergraduate researchers and iGEM teams in the Midwest region of the United States, where both of our teams are located. We proposed hosting a regional undergraduate research conference in which students from surrounding states would have the coveted opportunity of presenting their work. Alternatively, we suggested planning a local iGEM meetup in which local teams would be invited to an event spurring collaboration across projects and brainstorming about synthetic biology initiatives.

Heart Healthy Recipes on Instagram

Recipes to be Heart Healthy by the Michigan Synthetic Biology Team

We acknowledge that in addition to genetic factors like the rs773902 SNP, lifestyle choices play a key role in one's risk of cardiovascular disease, especially one's dietary choices. We promoted heart-healthy dietary choices on our Instagram with a compilation of a few recipes that aim to help reduce or prevent cardiovascular disease while still tasting amazing. We hope to show that heart-healthy eating does not have to be difficult or boring!

The Mount Sinai health system states that the goals of a heart-healthy diet should be to “obtain or maintain healthy levels of cholesterol and blood pressure.” In order to achieve this, a heart-healthy recipe should be low in saturated fat, simple sugars, and sodium and rich in nutrients. According to the Memorial Sloan Kettering Cancer Center, high intake of salt can increase blood pressure leading to hypertension, and hypertension is a major risk factor for cardiovascular disease. It is recommended that someone at risk for cardiovascular disease limit their salt intake to no more than 1,500 mg/day. Additionally, saturated fats can lead to the buildup of plaques in the blood vessels also contributing to cardiovascular disease. Saturated fats are predominantly found in dairy products and red meat. The USDA dietary guidelines recommend limiting saturated fats to less than 10% total daily calories. Intake of saturated fats can be reduced by choosing lean meats and low-fat dairy products or opting for healthier fats. Monounsaturated fats and omega-3 polyunsaturated fats are considered heart-healthy and can be found in nuts, fish, avocados, olives, olive oil, canola, soybean, or walnut oil. Finally, simple carbohydrates have been found to contribute to high levels of cholesterol. It is recommended to choose carbohydrates that are high in fiber such as fruits, vegetables, and whole grains. Diets that can help reduce or prevent cardiovascular disease include the DASH diet (Dietary Approaches to Stop Hypertension) and the Mediterranean Diet. More information can be found through the Sloan Kettering Cancer Center² and the Mount Sinai³ websites.

Meeting with Dr. Holinstat (Wet Lab Advisor)

Dr. Holinstat authored a paper that identifies the rs773902 SNP in the human PAR-4 gene as a key actor in platelet signaling, which differentiates along racial lines¹. We met with him to gain greater insight into his research and present our project plans to him. One of the important takeaways we had from his presentation to us included the use of appropriate terminology when discussing the SNP, such as using “abundance of the threonine allele”. We also discussed with Dr. Holinstat some other papers identifying PAR-4 as a gene of interest in thrombosis, as well as relevant statistics concerning the high correlation between race and genotype in relation to factors in platelet signaling.

Another takeaway was understanding the work being done to increase equity in clinical trials, an aspect his team is very conscious of. During the discussion, he noted that the U.S. Food and Drug Administration (FDA) issued a draft guidance in 2022 to increase enrollment of participants from underrepresented racial and ethnic populations in the U.S. into clinical trials. Our informative discussion with Dr. Holinstat fueled our decision to make medical equity a focus of our human practices work in relation to our project.

After Dr. Holinstat's presentation, we showed him our wet-lab plans for the project, including incorporating the use of LAMP and fluorescent probes for our SNP diagnostic test. We also discussed our cell culture testing plans for the project, and some of the limitations the team might encounter with timeline and safety priorities. We spoke about using a breast cancer cell line, and Dr. Holinstat offered our team a potential partnership to utilize blood samples for future testing.

Meeting with Dr. Smith (Clinician Advisor)

Dr. Eric Smith is a Clinical Instructor in the Division of Cardiovascular Medicine and a member of the Inherited Cardiomyopathy Program at the Frankel Cardiovascular Center at Michigan Medicine. His background in both electrical engineering and cardiology drew us to ask for his input on our project.

He advised us on the reframing of our project in the sense of treating it as a stepping stone in the direction of a multiple SNP detection system to consolidate multiple potential risk factors for cardiovascular disease. He was one of the main influences for our decision to build a database of SNPs, particularly in researching specific SNPs that are clinically relevant to hypercoagulability, or that contribute to a genetic risk of stroke.

Meeting with Dr. Deotare (Fluorescence Advisor)

Dr. Parag Deotare is an associate professor in electrical engineering and computer science at the University of Michigan. His primary area of research is in the development of low-energy photonic and excitonic devices for applications in data communication and life sciences. We explained our overall project to him and discussed with him specifics relating to our goal of building a low-cost fluorometer. We came to Dr. Deotare with a preliminary design, along with many questions we needed to answer before moving onto finalizing our design and beginning of prototyping. Our questions for Dr. Deotare included:

• How intense of a light source do we need?
• Do we need to focus light from an LED to the sample or is close placement enough?
• Is there a specific focal length we should go for with the lenses? What specific types of lenses should we be working with?
• Should we be using a prism or a filter to discriminate the light going to the photoresistor?
• Would we expect an issue where the light source drowns out the light emitted from the fluorescent sample, and if so how could we circumvent this issue?
• Is there any modeling software we could use to computationally model the system?

Per his advice, we opted to use a laser and photodiode instead of an LED and photoresistor. We discussed focusing light being a better choice instead of utilizing sample proximity to light source, as well as using a filter instead of a prism to discriminate light. It was incredibly helpful to get early feedback on our fluorometer plans, as it allowed us to save time on prototyping suboptimal designs, as well as work out a balance between cost-effectiveness and apt designs.