Integrated Human Practices

Integrated Human Practices

Feedback Loop (AREA Framework) We recognized the importance of effectively integrating stakeholder feedback into our project and closing feedback loops. To achieve this, we decided to adopt and adapt the AREA (Anticipate, Reflect, Engage, Act) framework, a structured and iterative tool widely used by research institutes to address social and ethical concerns in scientific projects. The AREA framework, originally created by Professor Richard Owen and further optimized by iGEM Team Exeter 2019 and iGEM Team TU-Eindhoven 2022, provided us with a systematic approach to process and integrate the valuable insights gained from our stakeholder engagements. We studied the framework and its previous implementations to understand its potential for our project. We further customized the AREA framework to suit our specific needs, focusing on how to best integrate the diverse feedback received from various stakeholders. Our adapted version maintained the four key steps of the original framework, which served as a guide for processing and incorporating the discussions we had with all stakeholders. This structured approach allowed us to systematically address social and ethical concerns raised during our engagements. Moving forward, we plan to consistently apply our optimized version of the AREA framework throughout our project development. This will ensure that we continuously integrate stakeholder feedback, close feedback loops, and address emerging social and ethical considerations. By doing so, we aim to enhance the relevance and responsiveness of our project to real-world needs and concerns, while maintaining a strong ethical foundation. This approach will not only improve our current project but also serve as a model for future iGEM teams in effectively integrating human practices into their work.


Results of Our IHP

For our BOOMcoli project, which aims to develop a novel ulcerative colitis (UC) treatment using engineered E. coli probiotics, identifying and engaging with relevant stakeholders is crucial to ensure our research addresses real-world needs and considers potential impacts. We have identified three main sectors of stakeholders:

To effectively map our stakeholders, we conducted an extensive brainstorming session and created an interactive stakeholder identification map. This approach provided us with a clear overview of all stakeholders and their mutual relationships essential to our project.

Dr. Georges Interview

Purpose:

Our team sought to gain expert insights into the ethical implications and real-world feasibility of our iGEM project. We reached out to Dr. Penelope Georges, a professor at Princeton University with a background in bioengineering and a focus on interdisciplinary studies integrating science, art, and literature. Her role as the Associate Director of STEM Initiatives for the Council of Science and Technology, combined with her expertise in contextualizing biological sciences in real-world applications, made her an ideal advisor for our project.

Action:

During our discussion with Dr. Georges, we explored several critical aspects of our project. She emphasized the importance of considering ethical implications, public perception, and education about our treatment methods. Dr. Georges advised us to examine the cost-effectiveness of our therapeutic and its target populations. She also highlighted the need to address the stigma surrounding engineered bacteria and stressed the importance of clearly communicating the risks and benefits associated with our engineered E. coli.

Implementation:

Based on Dr. Georges' guidance, we expanded our research to include the downstream effects of introducing E. coli to the gut and explored current methods of bacterial therapeutics. We incorporated her suggested questions into our project development, such as considering unintended bacterial competition, implementing an effective kill switch, potential immune reactions to bacterial lysate, and the possibility of passive growth triggering quorum sensing. These considerations allowed us to refine our project and address potential risks and bioethical concerns more comprehensively.

Future:

Moving forward, we plan to follow Dr. Georges' advice to reach out to physicians and biotech companies for more specialized information and advice on therapeutics and diseases. This will help us further validate our approach and ensure that our project addresses real-world needs while maintaining ethical standards. We also aim to develop a robust communication strategy to effectively convey the risks and benefits of our engineered E. coli to the public, addressing potential stigma and promoting understanding of our innovative approach.

All-Hands Meeting (1)

Purpose:

Our team organized an all-hands-on meeting, bringing together iGEM team members and our mentors. The primary goal was to provide comprehensive updates on our project's progress, share current findings, and discuss challenges across all aspects of our work. This meeting served as a crucial platform for cross-team communication and mentor guidance, ensuring alignment and addressing any roadblocks in our project development.

Action:

During the meeting, we presented detailed updates on various project components, including the quorum sensing, lysis, and therapeutics sections. We also shared progress on our mathematical modeling, human practices initiatives, and wiki development. Team members openly discussed the challenges and setbacks they were facing, seeking advice and support from both peers and mentors. Simultaneously, we celebrated our accomplishments, fostering a positive and motivating team environment.

Implementation:

Our mentors provided valuable insights during the discussion, particularly emphasizing the importance of adopting a patient-centric approach to our treatment development. They advised us to deeply consider how our treatment would impact the world and its potential users. Additionally, they suggested we start exploring ways to integrate our subteams more effectively, recognizing the interconnected nature of our project components.

Future:

Moving forward, we plan to implement the advice received from our mentors. We will conduct more in-depth research on the patient experience and potential real-world impacts of our treatment, incorporating these insights into our project design. We also aim to develop strategies for better integration among our subteams, fostering more collaborative work between the quorum sensing, lysis, and therapeutics sections. This integrated approach will not only enhance the cohesiveness of our project but also prepare us for the challenges of translating our research into a practical, patient-focused solution.

Bristol Myers Squibb Tour

Purpose

Our team visited Bristol Myers Squibb, a global pharmaceutical company specializing in cancer therapies, to gain insights into the process of transforming scientific ideas into commercial products for human use. We aimed to understand their approach to developing small molecule-based therapies for serious medical needs and to draw parallels with our own iGEM project development process.

Action:

During our visit, we learned about Bristol Myers Squibb's funnel model for drug development, which starts with thousands of candidate compounds and narrows down to a few FDA-approved drugs each year. We observed their learning cycle, consisting of design, synthesis, in vitro testing, and in vivo testing, which creates a continuous loop of optimization. This process resonated with our own engineering cycle of design, build, test, and learn phases in our iGEM project.

Implementation:

We applied the insights gained from Bristol Myers Squibb to our project structure. Inspired by their collaborative approach, where different teams work on separate domains of small molecules before combining efforts, we organized our iGEM team into three subteams focusing on quorum sensing, lysis, and therapeutic components. This division of labor allowed us to specialize in specific areas while working towards a unified final probiotic model.

Future:

Moving forward, we plan to incorporate the additional steps we learned about in creating a commercialized product. While our current focus is on in vitro testing, we now understand the importance of preclinical imaging, human dose estimation, and safety and risk assessments in the journey toward FDA approval and clinical trials. This knowledge will guide our future project planning and help us consider the long-term potential of our research beyond the iGEM Competition.


Dr. Brooks Interview

Purpose:

Our team sought expert guidance on our project focusing on gut microbiome therapeutics by interviewing Dr. John Brooks, Assistant Professor of Molecular Biology at Princeton University. Given his expertise in circadian clock interactions with the immune system and gut microbiome, we aimed to gain insights into the feasibility and potential implications of our proposed probiotic-based therapy for inflammatory bowel conditions.

Action:

During the interview, Dr. Brooks provided valuable insights on several key aspects of our project. He discussed the role of anti-inflammatory cytokines like IL-10, the specificity concerns of our quorum sensing system, and the potential impact of bacterial lysis on the gut environment. His expertise helped us understand the complexities of targeting inflammation sites directly and the importance of engineering our probiotic to be as specific to E. coli as possible.

Implementation:

Based on Dr. Brooks' advice, we decided to shift our project's direction from a "stick and lyse" method to a probiotic-mediated release of therapeutics. This change was inspired by the insights gained about the gut microbiome's delicate balance and the potential risks of non-specific bacterial lysis. We also narrowed our focus to ulcerative colitis rather than the broader category of IBD, allowing for a more targeted approach.

Future:

Moving forward, we plan to incorporate Dr. Brooks' suggestions into our project design. We will explore using calprotectin-sensitive promoters paired with quorum sensing for more effective therapeutic delivery. We'll also investigate the potential of administering our treatment at specific times of day, considering the circadian aspects of intestinal inflammation. Additionally, we'll expand our research into other potential applications, such as Celiac disease and Crohn's disease, and consider developing topical applications for conditions like psoriasis. This guidance has not only refined our current project but also opened up new avenues for future research and development in probiotic-based therapies.

Princeton Innovation Center Biolabs

Purpose:

Our team visited the Princeton Innovation Center Biolabs to gain insight into the process of transforming novel research ideas and biotechnology projects into viable businesses and startups. We aimed to understand the commercial aspects of biotechnology innovations and explore the potential pathways for patenting and securing funding for our research.

Action:

During our visit, we engaged with various stakeholders in the biotech industry, including investors, patent experts, and startup founders. These interactions provided us with valuable perspectives on the business side of biotechnology and the challenges of bridging the gap between academic research and commercial applications. We learned about the critical steps involved in patenting innovations and the strategies for attracting investment to further develop our research.

Implementation:

We applied the insights gained from this visit to our project by beginning to consider the commercial potential of our research. We started to identify aspects of our work that might be patentable and discussed potential market applications for our technology. This process helped us refine our project goals and consider how our research might address real-world needs in a commercially viable manner.

Future:

Moving forward, we plan to incorporate the business and patent considerations into our project development process. We will explore opportunities for protecting our intellectual property and consider forming partnerships with industry stakeholders. Additionally, we now know how to develop a preliminary business plan that outlines the potential commercial applications of our research, which could be used to attract future funding or support for turning our innovative ideas into real-world solutions. This experience has broadened our perspective, encouraging us to think not only about the scientific merits of our work but also its potential impact in the biotechnology market.


Dr. Cohen Mini Lab-Tales Meeting

Purpose:

We attended Dr. Daniel Cohen's Mini Lab-Tales meeting, a science communication series at Princeton University, to enhance our ability to effectively communicate our iGEM project to diverse audiences. Dr. Cohen, an Associate Professor in Mechanical and Aerospace Engineering, is passionate about science storytelling and emphasizes the importance of making research accessible while acknowledging the contributions of underrepresented researchers in scientific history.

Action:

During the meeting, we received training on transforming our research project into a compelling narrative. We learned techniques for integrating stories into research presentations, establishing an appropriate stage presence, and tailoring our communication style to specific audiences and goals. A particularly valuable exercise involved describing our iGEM project using only everyday language, challenging us to explain complex concepts in simple terms.

Implementation:

We applied the storytelling techniques learned in the workshop to our iGEM project presentation. By crafting a narrative around our research, we aimed to make our work more engaging and relatable to a broader audience. We also made a conscious effort to acknowledge the contributions of diverse researchers in our field, promoting a more inclusive approach to scientific communication.

Future:

Moving forward, we plan to incorporate these storytelling techniques into all aspects of our project communication, from public presentations to patient interactions. We recognize that integrating storytelling into science communication can increase engagement, foster a sense of inclusion, and build trust in science and scientists. This approach will be particularly crucial when addressing the public and potential patients about our treatment, ensuring that we can explain our work in an approachable and understandable manner while maintaining scientific accuracy.


All-Hands Meeting (2)

Purpose:

We attended Dr. Daniel Cohen's Mini Lab-Tales meeting, a science communication series at Princeton University, to enhance our ability to effectively communicate our iGEM project to diverse audiences. Dr. Cohen, an Associate Professor in Mechanical and Aerospace Engineering, is passionate about science storytelling and emphasizes the importance of making research accessible while acknowledging the contributions of underrepresented researchers in scientific history.

Action:

During the meeting, we received training on transforming our research project into a compelling narrative. We learned techniques for integrating stories into research presentations, establishing an appropriate stage presence, and tailoring our communication style to specific audiences and goals. A particularly valuable exercise involved describing our iGEM project using only everyday language, challenging us to explain complex concepts in simple terms.

Implementation:

We applied the storytelling techniques learned in the workshop to our iGEM project presentation. By crafting a narrative around our research, we aimed to make our work more engaging and relatable to a broader audience. We also made a conscious effort to acknowledge the contributions of diverse researchers in our field, promoting a more inclusive approach to scientific communication.

Future:

Moving forward, we plan to incorporate these storytelling techniques into all aspects of our project communication, from public presentations to patient interactions. We recognize that integrating storytelling into science communication can increase engagement, foster a sense of inclusion, and build trust in science and scientists. This approach will be particularly crucial when addressing the public and potential patients about our treatment, ensuring that we can explain our work in an approachable and understandable manner while maintaining scientific accuracy.


Jason Puchalla Interview/Meeting (Hardware)

Measurement:

We first asked Puchalla how to understand the dynamics of the microfluidic chamber so that we could apply what we learned to the gut. Puchalla started off by discussing measurements for the pressure of a straight pipe, which can be found using the Hagen–Poiseuille equation. This equation is not robust enough for the microfluidic chamber however due to all of its curves and different sizes throughout. Understanding the pressure of a more complicated system needs the use of sophisticated analytical modeling like the ComSol plug-in in Matlab. Rather than dealing with such factors, Puchalla advised us not to look at pressure but instead look at dwell time since what we are looking at is the amount of time the LB is in contact with the calprotectin agar. Such measurements are much easier to measure, usually being done by using a syringe pump to pump liquid into the system in a volumetric manner and to measure the output flow rate with a mass scale. This cuts down significantly on the complexity of our measurements while still providing enough data to transpose our results to a hypothetical.


Aurora Joblon Interview

Purpose:

We sought expert insights on quorum sensing (QS) in the gut microbiome and the safety concerns associated with introducing engineered QS systems into this environment. To this end, we interviewed Aurora Joblon, a graduate student in the Bassler Lab, whose research focuses on the molecular mechanisms of QS and its interactions with phages.

Action:

During our interview, Aurora provided valuable information on several key aspects of our project. She highlighted the complexity of QS pathways in different bacterial species, particularly noting the limited knowledge of E. coli's QS systems. Aurora emphasized the importance of specificity in our engineered QS system to minimize unintended effects on beneficial gut bacteria. She also discussed the correlation between invasive biofilms and ulcerative colitis, suggesting potential therapeutic targets.

Implementation:

Based on Aurora's advice, we plan to refine our approach in several ways. We will focus on making our QS system as specific to E. coli as possible to avoid disrupting beneficial gut bacteria. We'll also investigate the use of a lysis system similar to the VP882 vibriophage, which only triggers at high cell density. To address concerns about bacterial mutations evading lysis, we can design experiments to monitor bacterial growth and potential mutations over multiple time points after treatment.

Future:

Moving forward, we will expand our research to include experiments culturing our engineered bacteria with mammalian cells and wild-type E. coli to demonstrate specificity. We'll also explore the potential of using our system to induce biofilm formation in patients with low biofilm density, rather than solely focusing on lysis. Additionally, we plan to gather more statistical data on biofilms in IBD patients to strengthen our project's clinical relevance. These steps will help us address safety concerns and improve the potential for our therapy to be accepted in the pharmaceutical market.


NYU Virtual Meetup

Purpose:

We convened with the NYU iGEM team to review our projects and discuss their broader implications.

Action:

The session commenced with concise presentations of each team’s projects, followed by a Q&A segment designed to elicit deeper insights and constructive feedback. We were particularly captivated by NYU’s theme, which builds on last year's efforts to address low iron levels in women. They detailed their development process, which included computational work, a DNA assay, and an ELISA, with a current focus on creating a robust protocol.

Implementation:

The NYU team shared their experiences from the previous year, noting how three members collaborated effectively by dividing the judging questions among themselves. They also reflected on their goal of achieving a gold award and shared valuable lessons for future projects. Their insights, especially regarding the patenting of our work, proved instrumental in refining our research approach.

Future:

Moving forward, we aim to integrate the insights gained from the NYU team into our project development. Our immediate goals include refining our protocol based on their feedback and establishing a clearer timeline for our research milestones. We also plan to explore potential collaborations that could enhance our project’s scope and impact.


Presentation for Toettcher Lab Group Meeting

Purpose:

Our team aimed to receive feedback from experienced bioengineers to refine our project further. To accomplish this, we presented our project at a Toettcher Lab Group Meeting, led by Dr. Jared Toettcher, an expert in synthetic biology and cellular signaling at Princeton University. The Toettcher Lab focuses on using bioengineering techniques to explore complex biological systems, making it an ideal environment for gaining technical insights on our work.

Action:

The team met to create a concise and succinct presentation of our methodologies, experimental design, data analysis, and findings. During the meeting, we gave an overview of our project’s objectives, methodology, experimental results, and the potential therapeutic applications of our design. The bioengineers in attendance raised insightful questions about our system's regulatory mechanisms and the practical challenges of scaling our approach. Some members pointed out potential limitations in the robustness of our engineered cells when introduced into complex biological environments and emphasized the importance of optimizing gene circuits for specific environments.

Implementation:

Following the feedback, we revisited several aspects of our design, particularly the regulatory mechanisms that control gene expression. Although we didn’t have much time to redo our experiments, we adjusted our proposed future experimental plans to include more rigorous testing of system stability in fluctuating environments.

Future:

Moving forward, we want to explore more robust theoretical genetic switches to address concerns about scalability. Additionally, we aim to integrate more computational models to predict system behavior under varying conditions, ensuring our design remains practical and scalable.


Princeton Summer Research Symposium

Purpose:

We wanted to practice presenting our research to a more general audience that does not necessarily have a background in synthetic biology. We also wanted to gauge the clarity of our presentation and believed that the questions we received would identify certain gaps in our explanation.

Action:

We presented at Princeton’s Summer Research Symposium with the Omenn Darling Institute. We consolidated our most important diagrams and quantitative findings and graphs onto a poster and presented them to undergraduate students, graduate students, professors, parents, people from the Princeton area. We formulated the narrative to emphasize the importance of our project in the context of the need for better diagnostic and treatment methods for Ulcerative Colitis. We explained the technical terms that were important to our project.

Implementation:

We received great support from the audience! They also had many clarifying questions on our diagrams and graphs, so we identified ways to explain our project and results more clearly from the beginning. The audience was also very receptive to synthetic biology and medicine.

Future:

Moving forward, we want to revise our project’s narrative to emphasize the gaps in current diagnostic and treatment methods for Ulcerative Colitis and connect how our project aims to fill in these limitations. We also want to clarify how we present our modeling diagrams and graphs representing experimental data.


Presentation with Dr. Ellen Sherl's Lab with Cornell's IBD Center

Purpose:

Our team wanted to meet with experts who worked directly with people with Ulcerative Colitis to gain a patient-centered perspective on our project. We reached out to Dr. Ellen Scherl and Dr. Dana Lukin, two gastroenterologists associated with the Weill Cornell Jill Roberts Center for Inflammatory Bowel Disease. They work with patients who have IBD as physicians and clinical researchers, so we wanted to ask them if they thought patients would be receptive to our proposed treatment and other factors to consider.

Action:

We presented our project to Dr. Scherl, her lab team, and Dr. Lukin. They told us our ideas were exciting and that many people with Ulcerative Colitis are open to trying new treatments. They also mentioned an ongoing clinical trial for a treatment called Vedanta, or VE202, which is an oral probiotic containing strains of a bacteria called Clostridia. Probiotic treatments have great potential in treating IBD because of their localization to the intestine. They also gave us some important things to think about. For example, many IBD patients take zinc supplements, which could impact the effectiveness of our calprotectin-sensitive promoter. They also suggested that in the future we do more experiments to test the safety and effectiveness of our treatment by trying it on animals, like mice, in a controlled study with a placebo.

Implementation:

Although we met with Dr. Scherl and Dr. Lukin after we completed the experimentation, we used the advice that we received to adjust the narrative we presented when introducing our project. We realize that ingesting any engineered material, especially bacteria, can seem like a daunting idea to the population. By highlighting ongoing successful clinical trials using similar approaches and providing a clear explanation of how our treatment would function in practice, we aim to ease apprehension and emphasize the transformative potential of synthetic biology in medicine.

Future:

In the future, we aim to explore how our proposed treatment might interact with other treatments and supplements commonly used by patients with IBD. Additionally, Dr. Scherl and Dr. Lukin outlined the process of advancing a treatment from the lab to clinical trials, which presents an important area for further investigation.


Closing the Loop

The AREA Framework:

The AREA framework significantly enhanced our stakeholder engagement by providing a structured approach to integrating diverse perspectives throughout our project lifecycle. The framework's four steps - Anticipate, Reflect, Engage, and Act - were all crucial, but the Engage and Reflect steps proved particularly effective for our project. We engaged with a wide range of stakeholders, from patients and healthcare providers to researchers and industry experts, which allowed us to gather comprehensive insights. The Reflect step enabled us to critically analyze this feedback and integrate it into our project design.

We optimized the AREA framework for our unique project needs by emphasizing iterative engagement, particularly with medical professionals and patients affected by ulcerative colitis. This allowed us to continuously refine our approach based on real-world needs and concerns. We also expanded the Act step to include not just the implementation of feedback but also communication of our progress back to stakeholders, creating a more transparent and collaborative process.

The main challenges in integrating this framework were balancing diverse stakeholder opinions and managing the time-intensive nature of continuous engagement. However, these challenges ultimately led to a more robust and ethically sound project. The AREA framework was instrumental in addressing social and ethical concerns by ensuring we considered the broader implications of our work, from patient safety and accessibility to the potential environmental impacts of engineered probiotics. This comprehensive approach helped us develop a more responsible and patient-centered solution for ulcerative colitis treatment.