Human Practices

Ensuring our project is responsible and good for the world.

HUMAN PRACTICES

Responsible innovation along with Research and Development (R&D) is pivotal in the success of scientific work. Integrating human practices is essential in the development of a project, not only in terms of research but also in considering the wider implications on society. Stakeholder and general public opinions are necessary to help shape and evolve an idea. As researchers we have a responsibility to consider not only the scientific implications and benefits but also to consider the impact directly affecting others. Interactions with a broad range of stakeholders brings in knowledge from various backgrounds that will ultimately shape our project for the better while ensuring we are considering the opinions of those who truly matter.

Integrated human practices To implement the integration of human practices into our project, we endeavored to consider the perspectives of various stakeholders, dedicating time to reflect and adjust our project accordingly. Initially we sought ways to connect with healthcare professionals, academics, patient groups, and regulators.
The link to this section delves into the feedback we received and the corresponding modifications we made in response.
Ethics research As a healthcare-oriented project, ethical considerations were a primary focus for us. However, after encountering resistance in various forms, our approach to human practices underwent a significant transformation. This shift in focus led us to delve into the ethical approval process and its shortcomings, particularly within university education. This section brings attention to our perspectives, those of other iGEM teams, the importance of ethical research, the limited awareness among undergraduates, and our proposed solutions for the future. Our aim is to better prepare students within iGEM and the university as a whole when it comes to ethical considerations.
Closing the Loop Jump to this section to read the summary of how we brought all our human practice aspects together to close the loop between what was designed and what was desired.
Integrated human practices

Stakeholder meetings

Throughout the development of our project, we engaged with a variety of stakeholders implementing their feedback in ways that integrated into our research and experimental design.

Advice from Academics




See our final project idea here

Bootcamp week (14/06/23 - 18/06/23)

During our first week of iGEM, we received a talk on responsible innovation from Dr Andrew Morgan on the importance of using our project to solve a problem, which we used to help our idea generation. We also had a workshop with Sarah Hartley on the importance of integrated human practices, and including a wide range of stakeholders, helping us consider how our potential projects would affect the wider community.

Throughout the week we receive invaluable insights from our PI's, university lecturers and professors that ultimately shaped our iGEM project and encouraged us to explore research areas we hadn't encountered within our degrees before.


Description

We spent our first official week of iGEM learning about the competition and getting to grips with synthetic biology. We received a talk about innovation from Dr Andrew Morgan, where we learnt the importance of defining milestones and decision points during a project. Dr Morgan urged us to focus on the problem we were trying to find a solution to, and consider the value it would add compared to already existing solutions. We received a talk surrounding responsible innovation from Dr Sarah Hartley, which showed us the importance of integrated human practices. The session taught us that we needed to consider the impact of our project on a wide range of groups and stakeholders. We also learnt that a large part of human practices is communicating science responsibility, which is much more than just presenting people with information; instead, engaging with stakeholders and the general public in a way that allows them to express opinions and views is extremely important.

Throughout this week, with these talks in mind, we began brainstorming ideas for our iGEM project.


Feeling

The team were very enthusiastic to engage with the talks and lectures throughout the week, especially the key synthetic biology ones, which helped those who had not covered the content before get up to speed with the knowledge. As the week progressed, a lot of us were concerned about the amount of work that we were required to do, and unsure how we would complete it all. However, the talk from Dr. Andrew Morgan helped us to look at the project as milestones to complete instead of one massive task. With the fairly limited time to come up with an idea we were anxious about being able to achieve coming up with three fairly developed projects. However, after the first day of brainstorming, we were feeling more confident in our abilities as we found we could come up with quite a few ideas by bouncing thoughts off of each other.


Evaluation and Analysis

During our talk on innovation essentials, we were made to consider the need for a focus. Learning about research and development, emphasised the need for milestones as it would help focus our project and breaking it into manageable tasks. The emphasis put on identifying the problem we wanted to solve, helped to give us a starting point for ideation. It allowed us to come up with appropriate ideas that were more focused instead of just coming up with ideas and then fitting a problem to this.. This way of thinking forced us to consider existing solutions and whether our idea would add value. Through making the problem the centre of our brainstorming, what we wanted to achieve became clearer and our ideas became more sophisticated and developed.

The workshop with Sarah provided made us consider areas of science innovation that we hadn’t thought about before. With the content we learnt it has motivated us to consider the links to human practices our project could have and how best to approach it. In terms of our brainstorming, it helped to deepen our ideas research as we were now considering how we could implement responsible innovation and how it would apply to our project in an appropriate way.


Conclusion

Throughout the week we learnt about the iGEM competition and what was required of us. Through the various lectures and workshops, we learnt what a good team required, and that when trying to come up with an idea it is best to look at the problem wanting to be solved, as then it can give our ideas more purpose and focus. Going forward, we need to ensure that we are still implementing all of the points made to us about responsible innovation and research and development.


Action Plan

Moving forward, we plan to split off into three groups to extensively research our three ideas to understand the problem on a deeper level, and look at ways to combat it. We will practice delivering our presentation to our PI’s so they can give us pointers and feedback.



Summary

Dr Alan Brown made us consider the negative implications of using E. coli in our project, with Dr Katie Solomon reccomending using L. plantarum to engineer RIP instead as it was less controversial. We spoke to Dr Nick Harmer in regards to whether we could use HPLC to detect whether we had successfully produced RIP, and he advised us to speak with Dr Dyan Ankrett, the university's Experimental Officer for Mass Spectrometry. Dr Mark Clements also suggested using immunofluorescence as a RIP detection method.


Description

The focus of this week was idea finalisation, we aimed to complete a PowerPoint presentation of our three main ideas by Wednesday to present them to academics. We hoped the academics could help confirm the feasibility of our proposed ideas and aid us in deciding which to pursue. We split into three groups to research each problem. We looked at previous iGEM projects that could be related, and the research that had previously been done.

Our presentations included the background of the problem we were aiming to solve, current research, and our proposed solution. At the end of each presentation we encouraged the academics to ask questions and give feedback.Feedback for the first idea, a diagnostic test for acute Chagas disease, centred around how we would visualise the results and tackling the technicalities we had highlighted with the Oxford 2017 project[1], also on developing a test for Chagas disease. For the next idea, using magnetosomes as a drug delivery system into biofilms, it was highlighted that there was a lack of genetic engineering to the solution and so we should consider how synthetic biology is applied to the idea.

Finally, we proposed a preventative method for the formation of biofilms on catheters by targeting quorum sensing. There was concern about using E. coli on a catheter, Katie Solomon suggested using L. plantarum instead since it is a commensal which would be more ethically acceptable.


Feeling

Although we were confident in our preparation, having spent time researching and practicing our pitch, we were nervous as to how the academics would react. As this was knowledge that was quite advanced for us, we were slightly concerned about how well we would be able to answer their questions. After the presentation we felt a bit surer in our projects, especially as the advice given gave us some reassurance and promising leads to follow.


Evaluation and Analysis

The feedback given by the academics gave us new insight to our proposed ideas and helped to shape our decision on which one to take further.


Conclusion

After receiving the feedback on our proposed ideas, we took time to discuss which project we felt was most feasible and achievable. We chose to pursue looking at a way to prevent biofilms forming on catheters by targeting quorum sensing using the inhibitor RIP. However, instead of using E. coli to produce RIP, we took the advice of Katie and explored the possibility of using L. plantarum.


Action Plan

Next, we will look at extensively researching our idea as a whole group and making sure everyone is confident with the science behind it. As we have our project decided , we will look at how we could implement the human practice aspect and reach out to professionals to help shape our idea.




Reviewing our human practices

We discussed what we had already started in regards to human practices, and Sarah challenged our ideas, pushing us to consider the benefits of our project and what we actually wanted to find out. We were made aware that we required ethics approval to carry out the social science research we wanted to conduct, as we would possibly be dealing with vulnerable groups of people. The meeting opened our eyes to how much work we needed to do still, and despite feeling slightly overwhelmed, we were extremely grateful for the constructive feedback. We created a list of some things we needed to do, such as conducting a literature review to identify the gap in the social science research, and creating a stakeholder table. Access the table here.


Description

After Sarah provided us with some invaluable knowledge on responsible innovation in bootcamp week, we thought it beneficial to meet with her to discuss human practices implementation. During this meeting we discussed what we had already done in terms of reaching out to certain professionals and asked her advice. Sarah challenged our ideas and encouraged us to consider the benefits of our project and what we actually wanted to find out. We were made aware that we required an ethics form for certain social science research. It was also advised that we create a table to explain which are the relevant stakeholders, what we want to know, and what we already know.


Feeling

During the meeting we felt quite overwhelmed by all the things we had not considered and needed to. It was difficult not to feel that we had done poorly with the project so far, however, after digesting everything that had been said, we realised that we may not have considered the aspects Sarah had pointed out, but we now have a focus to work on. Also the meeting provided us with constructive feedback that could be used to further our project, so after, we felt grateful for the support and looked at ways to take the comments on board.


Evaluation and Analysis

The meeting was extremely insightful as it prompted us to think upon aspects we had not considered but would need to be successful. From Sarah's suggestions it was clear that we had a lot to look into, including the best ways to get the most out of our contacts. This includes careful planning and researching literature beforehand to make sure we are not asking questions where the answers are already available to us. In terms of the public, we need to check our assumptions and remain unbiased, by thinking about how we could discuss synthetic biology and our project without informing them in a one-sided way.


Conclusion

From this discussion we learnt that it was important to research what exactly we wanted to know from the different stakeholders and consider the demographic of catheter users. Before contacting anyone else we need to think further about this and conduct a detailed literature search to shape our discussions with stakeholders. We have been very focused on the science research that we slightly neglected the social research, meeting with Sarah emphasised the importance of carrying out social research as well.


Action Plan

  • Create a table detailing the various stakeholders that are appropriate to our project.
  • Research literature to underpin the social science experiments that have already been carried out and the results that they yielded.
  • From there we can identify what we want to know from each individual/organisation to make the most of our time with them. This is important as we need to be innovative in both science and social science.
  • Also, we will look at accessing an ethics form and fill it in for the scenarios where which one will be needed, such as contacting vulnerable groups.


When our project took a turn for the worse

We met with our PI, Dr Singleton, to discuss our iGEM idea as she had been away during our idea generation. During her own research, she identified some questionable components in the literature, and identified a controversy in the RIP-RAP-TRAP system we had planned to utilise. This made a lot of sense as Theo W and Bella had already faced this issue during their modelling of TRAP. While this left us feeling somewhat defeated, we powered through and started researching new methods of preventing biofilms. We also reached out to Dr Paul Williams, as reccomended by Dr Camara, who also suggested we use a different method of biofilm prevention. This was a big learning moment for our team, and we learnt that problems will arise sometimes, and that perseverence is needed to get through them.


Description

Our main supervisor, Chloe had been on holiday for the couple of weeks where we generated our idea and so we met with her to discuss what we planned to do and how we plan to achieve it. She did her own research and met with us to discuss some of the papers she had found. As Chloe had much more experiencing in researching, she was able to identify questionable parts of papers and knew how to conduct a well-rounded literature search compared to us. From this she had found a controversy around RIP/TRAP concept and explained how the system was contentious at best and non-existent at worst. From here we spent the next few hours reading over the papers she had found and understanding the findings.


Feeling

After the news that was delivered to us, we felt quite defeated and dispirited, especially as it seemed like the whole basis of our project had fallen through. When reading the papers that were directed to us by Chloe, we could see more and more flaws we had missed in this concept, and it was difficult to not feel like we had been set back a significant amount. It was hard to discern how we had missed what seemed to be a considerable controversy on the topic. However, as the day came to a close and we had finished looking into the literature, we acknowledged that although we had hit a complication, our project was not beyond saving, it is expected to run into problems, and we just had to remain positive and regard other pathways we could pursue.


Evaluation and Analysis

The literature revealed that the RAP/RIP/TRAP mechanism is extremely contested considering the original findings conducted by Balaban et al. [2]showed to be unrepeatable and questionable in various following studies[3][4], such as those conducted by Noveck et al.[5]In light of this, we decided to move away from using RIP as an inhibitor and instead focus on a new quorum sensing molecule and system to inhibit biofilm formation.

In addition to this, our team had encountered a few problems with being able to find a way to detect RIP and trouble around modelling TRAP. When ran TRAP through SnapGene and AlphaFold with RIP and RAP to model the binding to it, the results were displaying problems around the incompatibility. Therefore, before Chloe found the literature disproving the system, we were already questioning whether TRAP was the receptor or if it was just something that bound to another receptor. With our concerns regarding this concept, we reached out to Paul Williams, as recommended by Miguel Camara to see if he could shed some light on it. His reply followed similar lines to the problem Chloe had found and advised us to change our project. With both the advice from Paul and literature procured by Chloe, we looked at abandoning the Agr quorum sensing system and research further into a more feasible system.


Conclusion

In retrospect, this experience has been a valuable learning opportunity for our team. We've come to realize that challenges are common place in research, and the path is rarely linear. Instead of remaining disheartened, we focused on identifying what went wrong and how we could adapt to overcome this challenge.


Action Plan

In terms of our next steps, we plan on going back to researching the literature around inhibiting biofilms and moving away from the Agr system due to the amount of complications it has shown to have. We are thinking about looking into the LuxS/AI-2 system as it is found in both Gram + and Gram – bacteria, therefore, having the potential to fulfil our end goal of constructing a broad-spectrum biofilms inhibitor. It was also found that . plantarum, S. aureus and S. epidermidis have this quorum sensing mechanism and so it would fit in with our current project proposal. With this in mind, we will undergo a deep literature review of the system and evaluate whether the idea is a feasible one. Once we have considered a new way forward, we will reach out again to Paul to establish what his thoughts are and whether he could guide us in any way. Even though, we wish to shift our focus away from RIP, we will continue to clone the RIP sequences as planned as we already ordered the sequences. This will give us further experience with the protocols and better our laboratory practices while we wait for the new sequences to arrive for our newly formed idea.




Summary

We followed up with Sarah Hartley and discussed both the literature and the gaps in it, which would become our primary research focus. She gave us suggestions on conducting interviews, and encouraged us to consider how will integrate our research. She recommended that we present ourselves humbly, and to use our contacts’ time wisely. She also suggested that we choose one focus topic in our questionnaires to make efficient use of their time. The concept of maximum response with minimum input from the interviewee was proposed. We joined Facebook support groups as a way of spreading our questionnaires to catheter users via social media.

After our initial meeting, we felt more confident and were able to respond to her questions better. Although we were still slightly overwhelmed with all the work that needed doing, we now knew what we had to do.



Description

We met with Sarah Hartley for a follow-up meeting to discuss our progress on human practices research and plan. We talked about the social science literature we had encountered and the gaps that presented themselves – this would be our focus for any primary research we carry out. The feedback we received involved suggestions around interviewing individuals and urging us to consider how the research and data will be integrated into our project. It was suggested that we should present ourselves as humble and to see what our contacts have to offer while ensuring that we make use of the limited time they may have. Another useful recommendation made was to have a topic of focus in our questionnaires, as it is unlikely that our contacts will have an abundance of time to offer us. We appreciated that we need to be innovative to gain the maximum response with minimal effort from the interviewee.

Social media was also a suggested route to take and to attempt to engage catheter users on Facebook support groups to partake in our questionnaires. We needed to think of more creative ways to engage possible participants, there are other routes to follow that aren’t the traditional ones and we should exploit these for a maximum response rate.

Feeling

As we had taken the advice from the previous meeting with Sarah, we felt more confident in our research and were able to meet her questions with more surety. We appreciated the suggestions given to us and even though it was slightly overwhelming how much we had yet to complete; it was reassuring to know what we had to do moving forward.


Evaluation and Analysis

The suggestions given were an asset to our project and helped to re-focus our objective for integrating human practices from anexploratory approach to a responsible science one. It made us reflect on the ideas we had already formulated and reassess whether our questions were leading in any way and unbiased. During the discussion around how this research will shape our project, it was reflected that time was a major problem. This is one of the problems with human practices and the integration of them, the human practice side does not always line up with the science. By the time the feedback from our data collection comes back, we may not be able to fully adapt in response to it. This has been a key point for us to reflect on as we have learnt integrating the human practices earlier on in any project is a necessity and it has empathised the significance social science truly has on the practical science.


Conclusion

We gained significant advice from this meeting, and it was extremely helpful in clarifying where we needed to improve upon. It made our team realise how timing is significant in a project as not only is the scientific literature research essential, the human practices and social science is of equal importance and that to be successful both need to coincide with each other. One of the main issued we encountered that added to this time pressure was when we had to re-evaluate the basis of our idea around RIP/TRAP. This set us back slightly as we had not expected having to spend more time exploring further literature research. This meant that the human practices part of our project was temporarily put on hold to focus on a way around our encountered problem. We understand that our data collection would have been more beneficial at an early stage to our project, however, it will still help in validating the problem we are aiming to address and aiding us in considering how we could adjust our project to make sure it is responsible innovation.


Action Plan

Following this meeting, we plan to spend a day focusing solely on human practices, more specifically creating a final plan of who we are going to reach out to and what exactly we are going to ask them based off our stakeholder table that was written. We will take into consideration all the suggestions that Sarah made and apply them to any questionnaires and interviews we prepare to remain ethical in our approach and unbiased. As our human practice research involves healthcare professionals and patients, we need to go through the approval process of the University’s department of Ethics and Governance. Before contacting them, we need to know exactly what we plan on doing and how we are going to go about it.





Description

William Green is the innovation & partnership manager at the NBIC (National Biofilm Innovation centre). We wanted to contact William for multiple reasons, firstly, to discuss our project of biofilms and the associated catheter related infections, and secondly to see if William could point us in the right direction to possibly contact more people/companies that could help and guide our project. Going into this meeting we had multiple questions for William regarding his knowledge and expertise on the current frontiers in biofilm research, his opinion on where innovation is going in regard to catheters and biofilms, whether he thinks our project is feasible/applicable and many more.


Feeling

Going into the meeting we felt a little lost on who to contact with regards to modelling biofilms, if there are any universal AI-2 receptors in Gram positive bacteria, any catheter related companies and patients that use catheters. We were hoping to end the meeting with a variety of different contacts. After the meeting ended, we felt very positive and optimistic on who to contact. We were very happy to hear that William thought the general idea of our project was feasible and applicable, it just needed a little bit more research into the longevity of the coating/spray.


Evaluation and Analysis

William was very helpful. He gave us many different companies that we could contact, such as Smith+Nephew, and gave us some ideas on who to contact in terms of modelling, such the university of Glasgow and Cardiff which both model biofilms. William told us that we are on the right lines to be innovative. He explained to us that we may have identified a gap in the market of long term solutions to catheters. He mentioned that probiotics, even though may be a slight barrier, are an exciting field with increasing acceptance by both the public and doctors. We spoke to William about the coating/spray and how we could apply it to the catheter and William explained to us that it would be best to administer the coating/spray at the point of manufacture, as this would mean there would be less work for doctors/nurses to do. This would hopefully mean that doctors/nurses would be more likely to use this as there would be less work for them to do. Finally, William also sent us a follow up email asking us to fill out a document with our proposed idea and how NBIC can help with our project. He would then send that around to many different contacts that he knows for us.


Conclusion

Overall, we came out of this meeting very happy and very thankful for William’s time. William said to us that he thought our idea was promising, but we would need to get the past idea of using probiotics when describing our idea to specialists/doctors. However, he encouraged us by saying that probiotics are becoming more accepted in the science community and being more used. William also said that the NBIC would be happy to stay in contact with us over our 13 week project and urged us to sign up to the NBIC newsletter, which gives weekly updates about what NBIC are doing and funding opportunities.


Action Plan

  • Moving onwards with our project, we wanted to fill out the partner search document that William sent to us to hopefully get in touch with more people.
  • We need to do more research into how long the probiotic coating/spray would last. If we are using a spray, how long would the spray be ‘shelf-stable’. How much equipment would we need? And therefore, what would the cost of that be?
  • Finally, to get in touch with anyone that William recommends to us!



Advice on Laboratory work




Description

After reaching out to the University of Nottingham Molecular Microbiology professor, Miguel Camara about requesting expertise on biofilms and quorum sensing, we arranged to have a meeting over Microsoft Teams. Following the previous advice from Sarah, we had researched what we wanted to know, and had prepared topics to ask about, to gain a deeper understanding of biofilms and quorum sensing. Miguel was very helpful and provided us with some excellent insight and suggestions. We were looking at creating a L. plantarum biofilm to put on the catheters to produce RIP, however, Miguel explained that that wouldn't be necessary and instead we could upregulate exopolysaccharides expression to make the organism very sticky. He also urged us to think carefully about how we would market the live bacteria coated catheter to the public, we thought of taking the angle of explaining how L. plantarum is a commensal and already present in the environment in which catheters are inserted, as well as being a commensal.


Feeling

We felt that we could have used our time with Miguel more effectively but thought that the experience of talking to an academic helped us to understand what we needed to do next time to be more successful in our planning.


Evaluation and Analysis

Even though we had planned out what we wanted to ask Miguel, there was still a lack structure to our meeting protocol as he was under the impression that we wanted to understand the basics of biofilms. This was down to this being our first meeting with a professor online and initial miscommunication before-hand.


Conclusion

When planning the meeting, >we underestimated what Miguel knew about what we wanted from him, and there was a slight miscommunication initially. Although he provided some extremely helpful information, we did waste some of our time with him due to this fact. Learning from this, we need to better rehearse our meeting protocols and ensure that we are clearer in our initial outreach.


Action Plan

Miguel suggested opening a conversation with regulators as it may help with our proof of concept and provide an insight to whether our product would be accepted in a medical setting. We will contact a few other academics that Miguel directed us to. This included his colleague Paul Williams, who has more experience working with Gram positive bacteria, and so may be a helpful contact to reach out to for expertise. To ensure we make the most out of our time with other academics and professors, we will review how we planned this meeting and see what we should change about our process to avoid wasting time and making the same mistake. We will provide clearer information to the person we will meet before-hand to ensure everyone is on the same page so they can help us in the most efficient way.





Summary

At this stage, we were still focused on using RIP to decrease inhibition of mature biofilm formation. We were looking for a method to determine the successful synthesis and expression of RIP in our genetically modified bacteria when the time came, an issue we had come across in the literature, however, was the small size of the peptide. In an attempt to overcome this problem, we took on the advice of Dr Nick Harmer who suggested talking to Dr Dyan Ankrett, an experimental officer within the university.


Description

A few of our team met with Dr Dyan Ankrett, an experimental officer for mass spectrometry and High-Performance Liquid Chromatography (HPLC) at the University of Exeter to discuss the feasibility of using HPLC as a method of detecting RIP. As RIP is only 7 amino acids long, it was probable that it would be too small to detect on a Western Blot, which was our chosen method for detecting our other QSI molecules.


Feeling

As HPLC was something many of us had learnt about in our modules of study, the opportunity to possibly integrate it into our project was extremely exciting. The outcomes of the meeting were slightly disheartening as RIP was likely too big for HPLC and yet too small for western blot, so we felt a bit stuck with how we could detect RIP. We still had the option of using immunofluorescence as suggested first by Dr Mark Clements and then further supported by Dr Nic Harmer.


Evaluation and Analysis

During the meeting, it was established that RIP may be too long for HPLC and so would likely need to be digested into smaller peptides. This may be an issue if we wanted to detect RIP as an intact peptide and may also overcomplicate our project. It was suggested that we look into immunofluorescence and research further on how important it is for RIP to be intact. The column needed for detecting a peptide like RIP is unlikely to be owned by the university laboratory, but Dyan said that she would look into this for us. We also mentioned to Dyan that we had found a paper stating that RIP can be detected using HPLC depending on what column was used


Conclusion

The guidance given by Dyan indicated that HPLC may overcomplicate our project and so we should look at other ways to detect RIP that are simpler. Dyan also suggested to us to possibly move away from RIP and to contact her again if we are using a smaller molecule instead.


Action Plan

  • Our next steps are to investigate into other possible methods to detect RIP, starting with immunofluorescence.
  • Send the paper that we found to Dyan about detecting RIP using HPLC.




Description

Four members of our team met with the Experimental officer and Facility manager in Bioimaging at the University of Exeter, Dr Christian Hacker, to discuss the use of Scanning Electron Microscopy (SEM) to view and analyse our biofilms. We spoke about the process of bioimaging and prepping our samples, alongside discussions surrounding the best growth methods, materials and timeframes.


Feeling

This meeting was particularly helpful as we all gained a greater insight into bioimaging and the process of SEM. As a collective, we were able to establish specific dates and protocols necessary to get our biofilms imaged and analysed to gain proof of concept before the end of our project.


Evaluation and Analysis

Some issues raised by Christian surrounded the material we were growing our biofilm upon. Within our initial research, we had discovered that conventional glass slides and petri dishes grew weaker biofilms than 96 well plates. Glass slides did not seem to have any biofilm adhesion at all. This meant that the imaging would have to be done on small, fiddly wells, and the plates would need to be sawed apart. This was a concern of Christian’s.

We considered using silicone tubing to grow our biofilms instead. This would allow us to get a greater image without substantial DIY needing to be done. Unfortunately, we did not feel that we would be ready to move onto silicone growth within the time frame.


Conclusion

In conclusion, we agreed that SEM would be appropriate to use as a means of imaging our biofilm growth and reduction. We did, however, realise that gaining clear images may be difficult from within a 96 well plate.


Action Plan

The next steps for us as a team were to create strong biofilms in the 96 well plates that we could confidently give to Dr Christian Hacker to be imaged. We also investigated the possibility of using light microscopy to time-lapse biofilm growth with another member of the bioimaging office. Unfortunately, we decided against this process due to costs and our timeframe.




Ethical Considerations


It is imperative to evaluate whether any planned conduction of research, collaborations or surveys require ethical approval. Healthcare-oriented research comes with a variety of ethical considerations, particulary when involving any NHS services. As undergraduates with little experience around ethical and responsible research, we sought guidance from resources available in our university.
Unfortunately, it became a typical occurrence in our project to encounter a great deal difficulty in navigating this process. This difficulty prompted us to shift focus towards examining the current state of ethics teaching and regulation to see if these difficulties were system-wide. See here for more information on the matter.



Description

After spending a day solely focusing on the human practice element of our project, we contacted the Universities department of Ethics and Governance. As our discussions and interviews were to include the NHS, it was clear that we required this department to guide us on our options around gaining ethics approval and the feasibility of our human practice ideas. A meeting was proposed by the Department staff, and we met with them via Teams to further discuss our plans. During this meeting, we explained exactly what we wanted to do and asked for their thoughts around the necessary procedures we may need to follow.


Feeling

Before the meeting we were anxious around the feasibility of our proposed ideas, however, we felt confident in our preparation, especially as we had briefed the ethic and governance department around exactly what we planned to do in a prior email. We took extra precaution to ensure that this was a thorough and clear email stating our intentions after learning that preparation like this best ensures that we make the most of our time with our contacts from our experience with Dr Miguel Camara.


Evaluation and Analysis

Although the meeting was helpful, there were somethings that could have gone better. For instance, it was quite clear to us that our email was not read properly by the staff members we met with. Along with the department being the ones who proposed the meeting we were left assuming that they were clear on our plan and who we were, however this was not the case. This caused us to go around in circles for part of the meeting, leaving some of the meeting unclear and disjointed.

Despite this draw back, it was eventually determined that we did not require ethical approval for any of our proposed ideas as are approaches looked towards scoping for opinions being more akin to citizen service.


Conclusion

Once everyone was on the same page, the conclusions drawn were relieving and we had some clarity around our queries. We learnt the sheer complexity of the ethical process whenever carrying out research involving the medical workplace, it has given us an appreciation of the time consuming process. We also were able to comprehend what requires ethical approval and what does not. This meeting helped to further our work regarding human practices and enabled us to clarify what we need to work on next.


Action Plan

Following this meeting, we will request the statement of not needing an ethical approval for our human practice ideas in writing to ensure that we evidence for this and that it had been explained to us by the Department of Ethics and Governance. Once the bioscience ethics form is approved, we will begin contacting the people of interest for our research to establish connections for later interviews.



Ethics Research

Responsible and ethical research involving the integration of human practices is arguably the key to any research being successfully applied within society. Healthcare research and therapeutics holds ethics at its heart, making it a necessary element to any projects involving human and animal participants and samples. Ethical reviews and committees seek to protect anyone involved in or impacted by research from mistreatment or negative consequences. They work in the interest of participants and maintain their welfare.

With this in mind, the ethical considerations of our project were an integral part of our research. Comments shared by the Department of Ethics and Goverance (see above), while very useful in prompting us to think about the potential risks of our initial plans for human practices, were somewhat conflicting, length, and confusing at times. The process exposed us to the sheer complexity of university ethical reviews and promoted us to explore the origins of ethics and how it become so labyrinthine for researchers. The outcomes compelled us to reflect on our teaching experiences within university and acknowledge the lack of exposure undergraduates receive in relation to understanding the importance of human practices.

Our Experiences

Here, we will explain our experiences with ethical approval, it should be noted that this is purely what we experienced, we appreciate the vitality of ethics, there is no question of that, however the system could be better and this is what we want to convey. Sections preceeding this will convey what this experience lead us to follow and how we became more aware about ethical research, the gaps it contains but more importantly the lack of awareness researchers and undergraduates can possess and how this could be changed. We challenge the current systems, to promote for a future of universities with effective teachings of ethical research and proposals to better prepare future iGEM teams.

During our research, we initially wanted to conduct research that would be an addition to our human practices and as such we knew we would have to put our ideas through ethical review. In doing so we encountered a range of problems which we felt highlighted such an issue in the systems for research approval that it was worth spending time examining that process itself.

First, we were confronted with forms. We found that while trying to fill out the form not only was the form itself designed such that it was almost impossible for people to collaborate but the questions themselves often had very little clarification about the intended meaning, required amount of detail or what details would be most important. The questions themselves were often worded using specific yet ambiguous language like “Ensure quality and integrity”. Take the example of “research integrity” - there is a document on the university website titled ‘Statement On Research Integrity’ yet this gives neither a definition nor example of what this might mean in a question.

We did find a guide purporting to help you understand the process of research ethics, however, we were unable to access this as it was restricted. Despite not knowing the exclusion criteria of this document, it’s notable that undergraduates cannot view it. Other resources are available like consent forms/information templates on the research page yet these are reasonably easy to find in many places online and so are not much help in understanding the university’s specific guidelines.

With the incomprehensibility of the university’s ethical process, we were unsure if needed external approval we consulted the ethics people. In our initial meeting with them, it was established that we wouldn’t need external ethical approval, only the bioscience form. However, after issues arose from our bioscience form, the following meeting conceded inconsistent feedback compared to the previous. We reflected on whether these inconsistencies and lack of clear guidelines may be a common occurrence. There are seemingly clear enough instructions however the fact of so much confusion indicated that maybe there was an internal breakdown of communication or training.

To examine this further, we began conducting literature research on ethical approval processes investigating the history, issues and importance of such a process.

Other iGEM experiences

In light of the difficulties encountered navigating the university’s webpage for information on ethical approval, we sought to compare it to other UK university iGEM teams.

Firstly – KCL, similarly to Exeter, the information was lacking and was not adequately accessible. From an outside perspective, it gave the impression that with an internal log further information could be obtained and so it may be that the information around this process is clear and abundant, just not to an outside source. The criteria to access this information is based on whether you are a ‘KCL researcher’, however, it is unclear as to whether that means any students or just staff. Upon querying this, it was confirmed that the criteria were extended to all students and staff, a clear difference from Exeter’s restricted guide.

If you are an external researcher recruiting at KCL, there is a clear guide relating to the process required to obtain ethical approval. Condensed into one A4 page, the guide gives a concise overview of the process required to gain permission. However, it is stated that ‘It should be noted that this process does not constitute ethical review of the study, rather it is a permission procedure’ [6], which is unclear as to whether there is a further process required for external researchers.

After emailing a staff member within this department, their response was quick and forthcoming with information on the ethical process that is not mentioned on the external website. They explained that research falls into one of three groups ‘high risk’, ‘low risk’ and ‘minimal risk’. We were provided with a table categorising each group and the information was clear and identified the required steps needed for each category.

Universitas Indonesia

Compared to the regulations for ethical research in other countries such as the UK, Indonesia lacks tight regulations. Ethical research has a heavy focus on that within the health sector with the National Commission for Research and Development of National Health assisting the Health minister enforce such regulations. With this being the case, many of the higher education institutions lack the extensive ethical review process other such countries possess.

The research conducted by Fourianalistyawati et al. in 2018 [7] highlighted the variation in ethical research. They conducted a survey aimed at academics, the results showed that most respondents had knowledge of the importance of ethical research however 47.5% of the university's samples did not have an ethics committee. Interestingly, ethics committees that did exist were dominated by the humanities and social science despite this large stress and regulation on the ethics for the health sector. The paper notes the misconceptions between the committees and academics are apparent in certain disciplines with the respondents within healthcare having no misconceptions.

In terms of the comments made by the Universitas Indonesia, their experience highlighted this issue of misconception between their PI and the ethics committee, despite the previously mentioned study having no health sector misconceptions, it is clear that there are still misconceptions present. The Indonesia team has experienced these issues with ethical research mentioned in the paper first-hand and as a result, has impacted their research.

Bringing it all together: How we integrated human practices

Using the advice and feedback from professionals and academics, we shaped our project in accordance. In suppliment for talking to healthcare professionals and patients, we investigated any literature on our chosen problem and the solutions already available. As we could not talk to patients and doctors, we could not gauge whether the use a probiotic would be accepted as an alternative solution. To work around this, we looked to use a spray that incorporated our inhibiting molecules through the use of the T7 promotor. See here for how it went.

Professionals and academics

From professors providing potential develops to our initial ideas to William Green and Professor Miguel Camara discussing the specifics regarding biofilms, quorum sensing and CAUTIs, we implemented the advice and knowledge provided into our research and project. Paul Williams verified that there was a gap in the market for long-term solutions for the problems regarding biofilm related infections on catheters, and Dr. Katie Solomon suggested the use of L. plantarum instead of our initial plan to use E. coli, driving our research to investigate the probiotic and how we could engineer it to distrupt biofilms.

Professor Sarah Hartley

The role Sarah played within the development of our project was invaluable, her teaching on responsible innovation, drove us to appreciate this aspect of science in ways we had not before. The advice given developed and improved our strategies for human practices.

Dr. Dyan Ankrett

The input received from Dyan amounted to laboratory advice for how to conduct our assays, providing us with the necessary equipment to prepare our samples according to the required volumes to aliquot. Through demonstration of the LCMS machine, we were able to understand the mechanisms behind the assays. Before running LCMS, Dyan provided us with sample calibration curves, giving suggestions for the concentrations we should aim for in serial dilutions.The LCMS samples run by Dyan, gave our team the ability to detect the presence of standard molecules.

Department of Ethics and Governance

The comments stated from this department is what lead us to explore the foundations of ethcial research and comprehend the complexity of responsiblity in research.

Our review paper

Below is our paper we wrote highlighting our research in ethical research as well as our analysis of it within the context of university undergraduates and the iGEM competition.

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Our proposed solutions:
  1. Universities need to prepare undergraduates better for ethical research.
    Universities should actively seek to engage undergraduates with ethical research, empathising its importance and the elements that make up an ethical review.
  2. iGEM to introduce a workshop relating to ethical research for iGEM teams.
    After our experience in iGEM, we feel that teams would benefit from a workshop or seminar relating to human practices. We hope that this will help reduce the knowledge gap that is evident between teams.
    We appreciate that it would be challenging to hold a seminar of sorts to deliver this information, as teams begin their projects at different points within the year. Therefore, we propose a pre-recorded workshop that tackles all the considerations required for ethical research and explains the importance of abiding by it. We feel this will encourage teams to actively engage with ethical research and more attention can be spotlighted on human practices within iGEM. Even though not every team will have projects that require ethical approval, we believe it is important for all teams to be aware of this.
  3. Training for PIs on ethical research at iGEM
    We believe that it would be beneficial to iGEM teams if PIs had to undergo a form of training around responsible and ethical research to best equip teams that are not as familiar with the topic. As described previously around the difficulties faced by the Universitas Indonesia, it is evident that there are differences in the knowledge around the ethical process needed for research which ultimately limited this team's research efforts

In relation to bringing about more awareness of ethical and responsible research, three of our team presented during two lectures for first and second years. Here we spoke about the iGEM competition, our project and what we learnt in our research around human practices. We explained the importance of integrating human practices and attempted to bring awareness to the students about ethical research and the significance of it within scientific research. We hoped to provide the undergraduates with a brief overview of the lessons we wished we had been taught. There is a long way to go in relation to teaching ethics at university, but we thought that our presentation was a start to raising the awareness of ethics for these two cohorts of students.

images of people presenting
Closing the Loop

It is apparent that our human practices deviated from our initial plans and had to adapt accordingly. See the paper we wrote above to read about the research we conducted in relation to this and the solutions we propose. Despite our attempts to incorporate the opinions of the communities most impacted by our chosen problem, it was impossible to do so within our time-frame. From being told we could conduct informal chats with healthcare professionals by our REC then later this being contradicted by the same department. This end result came down to: we were not allowed to talk to any healthcare professional, NHS or private without external ethical approval that was would take months. In light of this we decided to investigate heterologous expression and enzyme purification to develop a spray instead of adhering a commensal, considering that we were unable to ask for the opinions individuals held towards probiotics. This was also encouraged by the comments articulated by William Green. See here for more information on the lab results.

With this said, we integrated the perspective of communities who require no approval procedures and implemented the advice and equipment they provided within our project. We identified that there is a lack of sufficient solutions for biofilm related infections in relation to catheters, with antibiotics the only method of treatment. It is clear this problem necessitates a long-term solution as the over-use of antibiotics is driving the top world problem of anti-microbial resistance.

We acknowledge that to be truly inclusive with our project, the next steps would be to undergo these external ethical reviews to be able to include the opinions of these communities, inviting their insight onto the daily issues met and whether synthetic biology would be accepted as a possible solution.

References ☆

  1. Team:Oxford/Future experiments - 2017.igem.org [Internet]. 2017.igem.org. [cited 2023 June 20]. Available from: https://2017.igem.org/Team:Oxford/Future_experiments?
  2. Kiran MD, Balaban N. TRAP Plays a Role in Stress Response in Staphylococcus Aureus. The International Journal of Artificial Organs. . 2009 Sep;32(9):592–9. DOI:10.1177/039139880903200908
  3. Shaw LN, Jonsson I-M, Singh VK, Tarkowski A, Stewart GC. Inactivation of traP Has No Effect on the Agr Quorum-Sensing System or Virulence of Staphylococcus aureus.Infection and Immunity. 2007;75(9):4519-27. DOI:10.1128/iai.00491-07
  4. Novick RP, Geisinger E. Quorum Sensing in Staphylococci. Annual Review of Genetics. 2008;42(1)541-64. DOI:10.1146/annurev.genet.42.110807.091640
  5. Novick RP, Ross HF, Figueiredo AMS, Abramochkin G, Muir T. Activation and Inhibition of the Staphylococcal AGR SystemScience. 2000 Jan 21;287(5452):391-1. DOI:10.1126/science.287.5452.391a
  6. Criteria for approval -External researchers recruiting at King’s [Internet]. [cited 2023 Sep 5]. Available from: https://www.kcl.ac.uk/assets/research/pdf/criteria-for-approval-external-researchers-recruiting-at-kings.pdf
  7. Fourianalistyawati E, Uswatunnisa A, Mahdiannur MA, Saleky AP, Soebandhi S, Reni A, et al. Research Development in Indonesia: Ethics Committee in Open Science and Collaboration Era. Journal of Physics: Conference Series. 2018 Nov;1114:012069.