Overview

One of the fundamental goals of MetraMorpheus was to be a people’s project. From brainstorming to implementation, we have closely involved our stakeholders. We took input from the stakeholders to design our project initially and regularly took their feedback on our proposed design. We then tried to close the loop between both through our implementation.

Interacting with people was a source of great inspiration. We integrated new ideas and suggestions for wet and dry labs, outreach, and the business model, sometimes even changing these aspects significantly. This made it possible to make our project better and push it towards excellence. It is amazing what we can achieve by broadening our horizons and implementing the gained knowledge.

During our project, we had multiple interactions with our stakeholders, taking and implementing new suggestions regularly. This helped us create feedback loops involving reflection, responsibility, and responsiveness between MetraMorpheus and the world. On this page, we have recorded the most important suggestions from the interactions with different stakeholders and how we took actions on the same.

Dr Rachit Aggarwal

Towards the end of our brainstorm, our seniors suggested us to contact Dr Rachit Aggarwal, from the Drug Delivery Lab at IISc, to know the feasibility of our delivery system. Dr Rachit has since been associated closely with the project, later agreeing to become our primary PI.

Suggestion: He suggested us to use LNPs instead of exosomes for delivery. He also provided us with papers for the same.
Action: The suggestion completely changed the course of the project. During the brainstorming, we had prepared a roadmap for an exosome-based solution, with an extensive literature review of 2 months. After his suggestion, we went through the papers and soon found out that LNPs would really be a better idea.
He also helped us in procuring the lipids, suggesting us to buy instead of trying to synthesize them. It also paved way for our transition to mRNA later, as one of the papers he had given discussed mRNA vaccines for COVID delivered by lipids.

Suggestion: He suggested us to provide him weekly updates to promote accountability of different groups and better planning.
Action: We have been making weekly targets and updating him since. Not only has it boosted our productivity, but also helped different groups convey their progress to the entire team, making the work proceed synchronously.

Suggestion: He suggested us to look into the clearance mechanism of scFvs in the body, methods to increase the circulation time of LNPs and IV vs IM as the mode of injection into the body.
Action: After the literature review suggested by him, we found out that it is possible to conjugate a CD47-mimicking peptide to prevent the unwanted phagocytosis of our LNP before it reaches the site. His suggestions helped us find a set of peptides that mimic the active binding site of CD47 that could potentially be conjugated to our DSPE PEG Maleimide. It has been added to our experimental design and we are yet to investigate this in detail.
Our scFv antibody, even when combined with IL8 and including the tags, has a diameter of less than 10 nm so that it can get cleared out from the body effectively through the kidneys. This, unfortunately, also implies a lower circulation time for the antibody. Hence, we are attempting antibody accumulation at the site and greater tissue penetration to make up for this. (The box dimensions are 7.2nm X 5.4nm X 9nm)
We also found out that the IV mode of injection would be a better choice for our purpose.

Suggestion: In order to develop a PK/PD model to figure out dosages for our therapeutic, he suggested us to look into “EPR” mechanism and how it improves retention of nanoparticles during diseases like cancer.
Action: We initiated a literature review to investigate EPR in cancers. This helped us draw parallels between cancer and endometriosis on the basis of inflammation, in order to predict efficiencies of our mRNA-LNPs. This also led us to try including FcRn in the linker of the scFv and we approached last year’s IISERP team for help.

Suggestion: He suggested us to find solid numbers for accumulation of LNPs in inflamed tissues and use numbers to come up with a rough estimate for optimal dosage.
Action: We collected existing data on LNP efficiencies and of other nanoparticles used in treatment of cancers and then went through the literature to find out protein release studies from mRNA-LNPs, helping us to calculate the optimal dosage. This is very important, because along with gathering data for research, we were also able to calculate the price of each dose for a successful business model.

Dr Dipshikha Chakravortty

Dr Dipshikha has been a PI for many iGEM teams in India. She has been closely involved with our project and has advised us since the brainstorming phase. She was our primary contact at the DBS, often helping us contact experts and manage the admin work too. She later agreed to join as a Secondary PI for our project.

Suggestion: The original name of our project was “Project Endometriosis”, with a minimalist logo. Dr Dipshikha suggested us to choose a name that echoes better with our concept, expressing our goal in a better way. She also suggested we remake our logo, including components of our proposed solution, such that the viewer can deduce it immediately.
Action: We brainstormed hard, finally choosing MetraMorpheus as our project name. Here's how we came up with the name:
- Metra means Uterus, and Morpheus is the Greek God of Sleep and Dreams: we are literally putting the disease to sleep!
- Metramorpheus is a play on the word "Metamorphosis", representing the change we aim to bring in the lives of millions of women worldwide.

We also changed the logo to include an mRNA coming out of the a lipid, and an antibody, representing O-IL8-15. It represented the proposed mechanism of action of our solution, and the final product that does the job.

Suggestion: When we proposed our workflow to her, she suggested multiple changes, especially the inclusion of controls at various steps of our project. She later gave us insight into the controls for steps like IVT and protein expression, such as introducing random stop codons in the middle of the CDS, so that we expect no expression from this in the supernatant. She also suggested us to use angiogenesis, tube formation assay and repeated confocal measurements to test hypotheses as to whether CD36 expression after producing a membrane bound protein is indeed recycled and whether repeated injections of the mRNA would be required.
Action: We introduced multiple controls in each of our protocols, the details of which can be seen on our [experiments] and [results] page. Not only did it help making our workflow more robust, but help us identify problems and rectify them promptly.

Suggestion: Before the All India iGEM Meet, we made our presentation to her, and she gave several suggestions, such as increasing the emphasis on human practices, improving the visual appeal and including page wise references.

Action: Our presentation underwent a major overhaul after the meeting, where we redesigned it entirely, increasing its visual appeal, adding proper references both in text and detailed and added 4 more pages of Human Practices. It helped us deliver a successful presentation at the meet, drawing praise from the judges and teams there.

Suggestion: Upon introducing the CD36 idea, she pointed out that macrophages might get recycled even without any extra peptides, since membrane proteins are energy demanding.
Action: The idea seemed to have a sound theoretical backing, and hence we undertook a literature review. We found the idea has not been tried before, and hence needs to be verified and we have added it to the tests needed to be undertaken. If successful, it would bring down the required number of doses and subsequent the cost of treatment, fulfilling our fundamental goal of making it widely accessible.

National Institute for Research in Reproductive and Child Health

Dr Shrabani Mukherjee: Dr Dipshikha suggested us to contact her to understand the effects of our treatment in physiological conditions. She suggested us to include more complex pathways in the future to identify novel targets to treat the condition. Hence, we made it our foremost goal in the business model to research new targets and expand our solution. She also referred us to Dr Geetanjali Sachdeva, the Director of NIRRCH.

Dr Geetanjali Sachdeva: She listened to our project keenly and gave useful feedback regarding its technicalities. Being an expert in the field of reproductive health, her approval to the IL8 idea boosted our confidence. However, for the CD36 idea, she asked us to check the glycosylation state when produced using mRNA. We added as a test to be conducted for the final treatment. For an immediate answer, we attended the mRNA symposium to understand about the ways that the best from industry and academia are producing proteins using mRNA. There, we got feedback from Professor Raghavan that glycosylation is usually not a problem in production of these proteins.

Nimi Vashi

We came in contact with Nimi through the WhatsApp group of iGEM India. She is a scientist at Epinoma, and has been an iGEM judge in the past. She advised our team at each step of the project, helping us make it successful.

Suggestion: She suggested us to watch the jamboree presentation of TU Eindhoven team from the last year and take notes for your project.
Action: The factors leading to the success of TU Eindhoven last year greatly influenced our project. It guided our optimisation in both planning and presentation to align with the judging criteria. Our coordinators tailored their strategies using the unique pointers from their presentation. This inspiration helped us refine our timeline, activities, and the project as a whole.

Suggestion: She advised us to create a better business plan that can take the project to fruition beyond iGEM, even if we are not competing for the special prize, as it gives a sense of completion to the project
Action: Our team worked hard on the entrepreneurship aspect of our project, contacting the Bangalore Bioinnovation Centre and SID at IISc to create a business model that is both profitable and sustainable in the long run. We also presented her with new avenues where the project could be expanded, like more diseases and Organ-on-a-Chip, and she gave very useful feedback on their implementation. Our business model can be credited largely to her suggestions and feedback.

Suggestion: She suggested us to check other diseases that can be targeted using our method. She explained how products don’t always work, and a business should have multiple avenues to earn.
Action: It led to the conceptualization of a broad mRNA based therapeutic platform, that can be used to produce targeted therapy for a wide spectrum of conditions. We are trying to treat TNBC, ovarian cancer and endometrial cancer, by developing scFv’s and dAb’s against IL6 (combination of IL6 and IL8 blockade are reported to give good results in these cancers). We have also developed anti PD1 scFv’s and dAb’s with the aim to reduce the abhorrent cost and possibly increase their efficacy. Hence, the advice not just improved our business model, but also led us to explore more avenues of research in the field.

Bangalore Bioinnovation Centre

Jitendra Kumar: He commented that attempts to create an mRNA based therapeutic, even if they fail, are essential. This is because mRNA based therapeutic system is non-existent in the country, and such projects would help in fostering further research. This motivated us further to explore more conditions that can be treated using our approach.

Dr. Ravikumar: He suggested us to add binding affinity test in the experimental design, to provide reliable data for the project. We implemented this and it became an integral part of our DBTL cycle. He also suggested us to explore in vitro translation for producing and testing out the scFv. This too became one of our final actions towards isolating O-IL8-15. He also told us about chitosan derived delivery system, an interesting research that he himself has worked on. He suggested we try this in addition to our initial approach of LNPs. Indeed, this cropped up again in the mRNA meeting, where it became clear that a few others in the Indian mRNA industry are also trying this out. We have added this as an additional avenue we would explore in the future.
Rita Sree Sarma: She explained to us the nitty-gritty of business and suggested us to pitch it as a femtech startup, a promising and novel market in India. She also suggested us to go for a B2B business model, focused on THC’s. She is a major influence on the development of our business model, as we included many of her suggestions.

Samarth

Samarth is a research scholar at IISc. He has been an integral advisor to the team since the beginning, forming our opinions on the various parts of the project.

Suggestions: He pointed out the gaping hole in our exosome idea, which was the unavailability of the targeting molecule. Though we had proceeded somewhat with our literature review, he stopped us from going too far into the implementation of the plan.
Actions: This is where we found about aptides, while trying to close the loophole pointed by him. Aptides became an integral part of our project, the backbone of targeting specificity we wanted to introduce.

Suggestions: He also looked at the paper from where our exosome idea had originated and recommended that we try interleukin 10 blockade, with a full-size IL10 Ab.
Action: We started exploring resources on the various cytokines that can be targeted. It was from this suggestion that the usage of the scFv against IL8 came to us, thus determining the core of the project.

Suggestions: He suggested that while presenting our idea to anyone, more visualisations of processes, and less text is desirable.
Action: Since then, we have tried to include more visualisations in our presentation, using posters, biorenders, etc. and minimise the text part. Not only did it help in explaining the project better to our stakeholders, but also helped a lot in our education efforts while presenting to young students.

Dr Subba Rao Gangi Shetty

While searching for solutions to loopholes that Samarth had given us, we contacted Dr Subba Rao Gangi Setty, a cell biologist.

Suggestion: He informed us of the issues of acquiring equipment to isolate exosomes, and synthesizing miRNA, making our initial idea extremely unfeasible.
Action: After understanding the complexities that Dr Subbarao pointed out, we had a long discussions with the team and dropped the initial idea. We then switched to our current idea based on the new findings as explained.

Dr Graca Raposo

While brainstorming our idea on exosomes, we came across a paper by Dr Graca Raposo, and contacted her for further advice. She appreciated our idea, specially the condition that we were targeting. She sent us the required resources to understand the possibilities and challenges. She was also the first to express confidence in our idea.
Action: We worked extensively on the literature she had sent us, and developed the idea to very good position, with proposed timelines and implementation. If not for the unavailability of the F8 Ab against Fn EDA, as pointed out by Samarth, we may have very well gone ahead with the idea.

Dr Siddarth Jhunjhunwala

Dr Siddharth is an immuno-engineer. We contacted him during the initial phases of our project after we decided to pursue a project in therapeutics and have taken valuable feedback from him since then.

Suggestion: He suggested us to look for shorter sequences as they are better in many respects, and gave us resources to start with.
Action: One of his papers mentioned about scFv’s, which are smaller than conventional Ab’s. We incorporated these scFv’s everywhere in our project, and later tried dAb’s too, which are even shorter sequences. This helped in shortening our mRNAs too, which were then encapsulated better inside the LNPs, giving an additional advantage.

Suggestion: He suggested us to incorporate a signal peptide in our sequence for secretion.
Action: We incorporated CD33 signal peptide after extensive background research , which can be found on our engineering page.

Suggestion: He suggested us to incorporate N1-methyl pseudouridine, which his lab has proven to reduce immune response.
Action: We incorporated these modified sequences, and have planned to test the immune response ourselves using various assays.

Dr MK Ammembal

Dr Ammembal is a member of the Royal College of Obstetricians and Gynaecologists and an established expert in the field of Endometriosis. He introduced us to the severity of the condition, and the existing treatments with their problems.

Suggestion: He laid down the clinician’s perspective on what an ideal solution should be. This included:
Should not interfere with the fertility
Should have multiple administration options
Should not increase the risk of gynaecological malignancy
Recurrence should be almost 0 for atleast 2 years after the therapy
Should arrest progression of DIE

Action: Since the beginning, we strived to fulfil the conditions he had given. Our brainstorming, design and implementation focused on achieving these goals.

Vinod and Lavanya

[Lavanya]
Dr Vinod and Dr Lavanya were our lab supervisors during the project. They played a major role in guiding our lab work, often helping us procure reagents and assemble our experimental setup.

Suggestion: At the very beginning of our wet lab, they gave us a session on how to arrange the lab, with proper guidelines for handling machines and storing reagents, buffers, etc.
Action: We implemented the suggested lab techniques since the beginning. It boosted our productivity and helped in keeping a record of stuff being used up. We also added labels to all the shelves, helping new members navigate easily.

Suggestion: In the initial days of our project, we were using TG1 strain for all of our bacterial work,from cloning to protein expression, because of their easy availability. However, we were observing poor efficiency in both processes. They suggested us to use BL21 and DH5a instead of TG1 for protein expression and plasmid cloning respectively
Action: We did as instructed, and indeed the efficiency improved manyfold. We also stored both the strains at -80 ̊C for the use by future teams.

Dr Christian Andrew Choe

After finalising our mRNA and plasmid sequences, we were searching for a more innovative method to extend the lifetime of the mRNA. We came across an interview of Dr Das from Stanford University on an algorithm to optimise the mRNA sequence to increase its longevity. We contacted him, and he referred us to Dr Christian for details about the Ribotree tool.

Suggestion: We explained to him that we do not have the time or resources to perform IVT repetitively, and hence wanted to use Ribotree. He walked us through setting up RiboTree and suggested some settings that might work for us.
Action: Ribotree helped us a lot in optimising our mRNA, details of which are on the Modelling page. Also, we helped in fixing multiple bugs in their software and its dependencies. We are now creating a Docker Image to allow easy installation of RiboTree and reproducibility of results. We plan to get back to Das Lab and suggest they provide this image in their distribution.

Amar Singh

We wanted to utilise the GRAMM web server for protein-protein docking. To seek help regarding the technicalities and other aspects to take care of, we contacted the Vakser Lab at University of Kansas, where Amar Singh agreed to have a meeting with us.

Suggestion: We asked him about the AACE18 and shape complementarity scores from template-based docking and free docking on GRAMM to compare the two results. Also, whether the data can be converted to actual energy units. Amar suggested we use docking interaction energy estimation software like PRODIGY and provided us resources demonstrating the accuracy of GRAMM compared to other similar tools
Action: We used GRAMM and it became the most important software in our docking analysis. Our results can be seen on the Modelling page.

Nisha Barge

To clarify our initial doubts about dry lab, Dr Rachit referred us to Nisha, who gave us great insight into pharmacokinetics and protein modelling.

Suggestions: She suggested us to look at simpler and similar models as discussed in literature. For example, pharmacokinetics of PEG polymers, siRNA-based solutions, etc. She further suggested that we choose a “template” that is closest to our human protein and pointed out that we will have to check metrics like rate of uptake of particles, site of injection and delivery to target cells, kinetics of polymer particles, hydrophobicities, release kinetics of our antibody, etc. She also provided us with online resources to get acquainted to some concepts in Pk-pd.
Action: Much of our dry lab was based on these fundamental suggestions. We implemented her advice partwise, forming various subteams to focus on each part. For further information on the incorporation of these ideas, check our Modelling page.

RR Ojha from QUAXON

After a conversation with Nisha, to understand the fundamentals of docking, we contacted Dr RR Ojha, an expert in the field of homology and docking.

Suggestions: He told us about the importance of protein folding, fundamental assumptions and principles of homology modelling, and the steps to be taken for it, from template recognition to model validation. He also provided us a list of softwares that can be used.
Action: Our entire modelling has been done following the steps underlined by him. We also used and compared the various softwares he listed, and uploaded the results on the Modelling page. The workflow he provided us helped in making our actions robust and efficient.

Nandika Bhattacharya

When our initial attempts at BLI failed, we contacted Nandika, who has been conducting research on scFv’s in an attempt to fix the problems with our experiments.

Suggestions: She pondered for long on our design and then identified the probable problem to be in the formation of disulphide bonds. She gave us multiple ways to troubleshoot the problem:
1. Check the level of expression that cell can tolerate by inducing with different concentrations of iptg
2. Use PelB signal peptide to express protein into the periplasmic space, as proteins would have higher chance of sulphide bond formation, or use shuffle cells, that can make disulfide bonds in cytoplasm itself without any signalling peptide. This is easier because it would only require a simple lysis to get the protein out.
3. Try larger volumes to get higher concentration at the end
Action: We induced our cultures with various concentrations of IPTG and got a positive result in western blot for all of them. We also tried larger volumes, culturing 1L at a time, however, the results were the same. We are trying to procure shuffle cells, after which we’ll clone our sequence on a new vector and proceed with the expression.

Vinayak Annapure and Shreya Kulkarni

After getting the advice from Dr Rachit, we contacted Shreya who was a member of IISER Pune team last year that worked on producing recombinant antibodies. We had an online meeting with her and her teammate Vinayak, where they gave us various tips to increase the circulation time of these antibodies in the body.

Suggestion: Vinayak told us about the kidney filtration pathway, kidney charge bias and the FcRn mechanism. He provided us with multiple resources and papers to understand these better and find ways to make our antibodies last longer.
Action: We went through the resources he provided, and realised multimerising the scFv’s is the easiest way, as the kidney filters everything small, and these large multimers can escape it. We have also added these in our workflow to be performed in the later stages combined with dry lab modelling.

Dr Raghavan Varadarajan

Dr Raghavan is a prominent biophysicist and an expert in mRNA vaccines. We contacted him when we started considering mRNAs as our solution, and have taken his help regularly since then.

Suggestion: He gave us the initial design for mRNA construct and other tips to design it successfully.
Action: His experience in mRNA vaccine proved to be of great value and we based all our designs during the project on the construct.

Suggestion: When our initial attempts of protein purification were unsuccessful, he suggested us to add Ammonium Sulphate precipitation to the protocol.
Action: We added it to our protocol, and saw significant decrease in effort required to purify proteins to the required concentration.

Suggestion: Answering the question about glycosylation asked to us by Dr Geetanjali, he told us that it is not a problem in most cases. However, he also mentioned that the glycosylation patterns may vary based on the cell type. Through literature review, we realized that this has not been tried sufficiently yet, and that introducing mRNA into immune cells is a question yet to be solved.
Action: We have added this to our plans of testing, to see both in vitro and clinical effects.

Suggestion: Suggested us to do BLI instead of SPR, because SPR is costly, and would require significant time to learn and undertake.
Action: As we were low on time left in the iGEM cycle, we accepted his advice and conducted BLI, thus changing our initial project design, getting enough binding efficiency data.

Suggestion : Moderna UTRs are the shortest and have the highest efficiency.
Action: Our project incorporated Moderna’s UTRs, and we also found ways to develop our own UTRs inspired by them.

Dr Ajay Singh

Gennova are the makers of the first mRNA vaccines approved in India. We met Dr Ajay, mRNA Development head at Gennova, during the mRNA conference held at IISc.
Our Question: How to develop our own UTRs, especially considering Moderna’s patent.

Suggestion: Though Moderna has a patent on UTRs, they have taken human betaglobin sequence, and it is not possible to patent natural products. So technically, we can take the original sequence and modify to develop our own.
Action: We have started the process of making new UTRs, and taken this into consideration while making our business model.

Dr Ramray Bhat

Dr Ramray Bhat is a developmental biologist, who also has experience with Organ-on-chip models. We consulted him to find the feasibility and technicalities involved in developing a successful model ourselves.

Suggestion: He told us that he has a peritoneum on a chip model, and we can adapt it to our use by just replacing the endothelium with mesothelium cells to undertake the initial tests.
Action: This ingenious solution would indeed have helped us get the preliminary data, and we started with the planning to implement it. However, we realised it would be quite difficult to procure the mesothelium cells, and hence needed to find other solution

Dr Prajakta Dandekar

While searching for alternate ways to undertake the Organ-on-a-Chip, we came across an article on the research of Dr Prajakta. We contacted her and had an online meeting where she gave us very useful insights into developing our model.

Suggestions: She suggested we should first decide our goals and results we want to extract through our OoC and then design our device based on them. She also suggested us to identify the physiological conditions of the uterus to imitate them in our model. She further told us to look out for the industries in the field to understand the details of proper implementation.
Action: We planned our OoC primarily based on her suggestions, including cocultures, multi-channels, and the stimulating factors to be considered.

J Konnowich

Upon finalising the basics of our OoC based on Dr Prajakta’s feedback, we started to look out for industries in the field, who can provide us with the technical expertise to implement it successfully. Hence, we came in contact with J Konnowich from Emulate.

Suggestion: He made a visualisation of the OoC we needed, and also gave a quotation for the same. He also explained how modifying existing systems is cheaper for both development and manufacturing than starting from scratch.
Action: His visualisations helped us understand the mechanism of 2 channel flow better, which we incorporated into our model. We also realised the business scope of OoCs, and the ease with which we can expand in it, specially in an untapped market like India. We included this in the entrepreneurial aspect of our project.

Education Secretaries

With the target of including synthetic biology in the curricula, we contacted education secretaries of various states. We had meetings with the Education Secretary of Jharkhand, Shri K Ravi Kumar, and Karnataka, Sri Ritesh Kumar Singh and Mrs. Ranjana Arora, Committee member at the National Council of Educational Research & Training, the state book publisher of India.

Suggestion: We should look for already existing chapters where biotechnology can be incorporated, because introducing new chapters might increase the academic load in students.
Action: We prepared a list of chapters in various classes where applications of biotechnology related concepts were being taught, but without directly mentioning it, and suggested ways to represent its scientific aspect better. For example, students are taught about the Green Revolution in India in various subjects, we proposed a small snippet with information about GMOs to be included with it.

Suggestion: They suggested us to organise a bigger campaign parallel to the curriculum to capture the people’s imagination. Something akin to the International Yoga Day, which has become quite popular.
Action: We considered a few choices like the National SynBio Day and National Biology Day. But they seemed either too narrow to gather the initial support or too broad to focus on our message. Finally we settled on the National Biotechnology Day, a topic fairly known among the people, yet with the capabilities to add new enthusiasts.

DD Interview Panel

We conducted a show on Doordarshan, the state broadcaster of India, in Jharkhand, one of the most backward states in the country, both economically and socially. The panel consisted of the host Mr Madhukar from the channel; Dr Suman Sinha, a gynaecologist; Dr Nasreen Jamal, Chief of Project at ICMR Jharkhand; and Shloak Vatsal and Sheersh Sen from our team.

Suggestion: The panellists informed us that the people are generally sceptical about these new solutions, and we should ensure we gain this trust. This is specially important in backward states like Jharkhand, where education is not very prevalent, and practices like jhad-fuk still exist.
Action: Our approach, hence, also turned towards promoting awareness about synthetic biology, apart from endometriosis. We also invited multiple experts to public talks, to validate our methodology, and ensure people of its reliability.

Suggestion: They told us that the conditions relating to women’s health are considered taboo, and hence most people, except specialist doctors, do not discuss them.
Action: “A picture is worth a thousand words”. We tried to achieve something through art in a few months, that words haven’t achieved in years. We tried to make our theme appealing to the people, so that it can attract a larger audience, and makes them talk about these issues. We made comics to make the explanation fun and easy. We also created detailed brochures, with illustrations, stories and interviews, to allow the people to delve deeper if they want to.

Suggestion: The show was in Hindi, and we faced trouble explaining many a things due to this constraint. It was then that Mr Madhukar, somewhat mockingly, suggested us to look up the translation of these words.
Action: We realised that our fundamental goal of making MetraMorpheus a people’s project can’t come true, unless we communicate it in the people’s language. We launched a language project, translating our content into 18 Indian languages, covering 93% of the population. Our next goal is to ensure these become available in every school and health centre across the country.

Dr Lavanya Bhagavatula

We met Dr Lavanya at the All India iGEM meet. She has been the PI of past iGEM teams of IISER Bhopal.

Suggestion: In order to make a better project, we should include more people at IISc, especially outside the UG circles, as it would bring their expertise and experience, as well as exposure to more problems.
Action: We started with events like CS Club launch and sessions with the Biology club at IISc, but soon realised that these too are majorly attended by UG students only. Hence, we collaborated with the Quiz club to organise a synbio quiz, and organised an iGEM symposium, to spread the word about iGEM in newer circles.

Suggestion: The iGEM cycle should be started before the previous one ends. This leaves room for errors and more brainstorming. It also gives teams time to undertake human practices better, as they can plan out long stretched campaigns.
Action: We organised the orientation in August, soon after returning from AIIM. We also organised multiple programs and events like the ‘Rising Dry Lab’ to help the interested students start early, and gain experience.

Dr Shilpa Rao

While identifying our stakeholders, we understood that it is our foremost responsibility to contact the patients, who have seen the horrors of endometriosis firsthand. We found about Dr Shilpa through her awareness posts on social media, and she was a major influence on our project, guiding and inspiring us at the same time.

Suggestion: She told us that Endometriosis is not just a disease of the body, but also affects the mental health of the patient immensely, and we should keep this in mind while talking about the condition.
Action: The narrative for the entire duration of our outreach has focused equally on the physical and mental strain associated with endometriosis. This can be seen in our talks, interviews, comics and brochure.

Suggestion: She stressed the importance of early diagnosis to keep the effects of the disease under control.
Action: We started a collaboration with Utero Diagnostics, to make a complete solution for Endometriosis including both diagnostics and therapeutics. We also contacted the other iGEM teams like IIT Roorkee and IISER TVM to pursue a joint endeavour with their biomarkers based diagnostic project.

Suggestion: She underlined the fact that talking about such conditions concerning women’s reproductive health is considered a taboo and hence many misconceptions build around it which need to be countered.
Action: In our brochure and outreach we included separate sections discussing misconceptions relating to the condition. We hope it would be helpful not just for the people, but also for general physicians and health workers who are the first points of contact for these patients.

Dr Abhishek Mangeshikar

Dr Mangeshikar is the Founder and Director of The Indian Centre for Endometriosis. He is an avid supporter of surgery and we approached him for this reason only, to know his perspective on a new alternative solution.

Suggestion: He explained his point why currently excision through surgery at the earliest stage is the best way to treat Endometriosis, even after its side-effects. He pointed out the lack of consensus among gynaecologists and the hand of the pharmaceutical industry to promote the futile attempts of hormonal therapy being prescribed.
Action: This changed our initial outlook towards surgery, and highlighted even further the dire need to develop a non-invasive treatment. It also made us realise that our treatment, even if effective, will take some time before being adopted by the doctors. This greatly influenced our business model, where we must assume the real case where our treatment would not be miraculously adopted everywhere, but would need gradual expansion, winning the confidence of doctors and patients alike, while countering the false narrative of our competitors.

Suggestion: He dismissed retrograde menstruation as the main cause behind endometriosis, quoting Dr David Redwine’s study where endometriosis occurred even after Mullerian anomalies.
Action: This really triggered us to ponder on alternative causes of Endometriosis, especially concerning the immune system of the body. This then led to the conceptualisation of the CD36 idea, where we want to activate the macrophages to destroy the endometriosis-affected tissues.

Suggestion: He explained to us how endometriosis can actually invade other parts of the body, as it progresses in various steps.
Action: This gave us a new perspective of endometriosis, and made us realise why the antibodies should stay longer in the body. After this, we actively pursued the target of increasing the longevity of our treatment.