Integrated Human Practices

As team iGEM IIT Madras, we value how our project impacts the research being conducted in labs worldwide as well as how we can apply it to various industrial domains including food and cosmetic technology, production of recombinant proteins for therapeutic purposes and biomanufacturing. To ensure that our project for this year’s iGEM is relevant for scientists and industries, we took initiatives to meet them and get their feedback as regards to how we can improve our project. For development of our webtool, we also approached the author, Dr. Salis who worked on developing the popularly used RBS Calculator. Based on his inputs, we detailed our model further. To ensure that our project can be scaled up, we had talks with various well known companies like Biocon and incorporated their inputs. We are optimistic that our project will greatly help researchers and industrialists in fine-tuning gene expression and getting higher product yields.

A meeting with Professor Victor de Lorenzo

Our lab team had the opportunity to interact with Dr. Victor de Lorenzo, a highly esteemed synthetic biologist from the National Biotechnology Center in Madrid, Spain. During the discussion we presented our project idea in order to obtain his invaluable feedback and insights.

We were pleased to find that Dr. de Lorenzo was enthusiastic about our proposal to develop a novel genetic engineering toolkit for an unconventional chassis. Further, he expressed his satisfaction with the progress our team had made up to that point in terms of laboratory work as well as computational analysis.

One of the key insights from the discussion was his suggestion to incorporate the effect of species-specific RNases while building a predictive model. These RNases, which are unique for different species, may play a significant role in translation efficiency and including their effect in the model could lead to more accurate predictions. Additionally, Dr. de Lorenzo proposed the utilization of an in vivo recombineering tool to expand the size and diversity of our ribosome binding site (RBS) library. This would enable us to diversify our toolkit more effectively.

The meeting was an invaluable experience for our lab team and we are deeply appreciative of his generosity in sharing his insights and suggestions. The team is grateful for his enthusiasm and guidance, which has not only enhanced the scope and relevance of our project but has also left us inspired and motivated to further explore the boundaries of synthetic biology.

A Correspondence with Professor Howard M. Salis

Our team has the broad goal to develop a library of synthetic ribosome binding site (RBS) sequences for fine-tuning protein expression in Lactococcus lactis. The project also included the creation of an in silico tool to predict the expression level of a gene and optimise its RBS sequence to achieve a desired expression level. Additionally, we wanted to explore applications of RBS engineering in the development of a probiotic treatment for homocystinuria and in the modulation of the molecular weight of hyaluronic acid produced by recombinant L. lactis.

Seeking expert guidance, we reached out to Professor Howard Salis, a prominent figure in the field of synthetic biology, and the creator of the widely used RBS Calculator. The correspondence between our team and Prof. Salis unfolded over several emails. We reached out with a set of specific questions regarding his RBS Calculator and its applications:

1. Incorporating the effects of RNase-mediated degradation and mRNA-S1 protein interaction.
2. Differences in the model's performance between FlowSeq data and individually characterized RBS sequences.
3. Choosing a dataset to compare their model's performance with existing models.
4. Considering separate translation initiation models for Gram Positive and Gram Negative bacteria.
5. Adapting the approach for rational RBS sequence design to different chassis.

Prof. Salis graciously provided detailed answers to the team's questions:
1. Prof. Salis explained the interdependence of mRNA's translation initiation rate and degradation rate in the project. The degradation rate relies on the translation initiation rate predicted by the RBS Calculator.
2. He clarified that performance disparities stemmed from variations in experimental techniques. FlowSeq's methodology could lead to variations due to weighted-average calculations, while individually characterized cells offered more accurate statistics.
3. Prof. Salis recommended using individually characterized cells for model comparison, emphasizing the importance of reliable and robust data for validation.
4. He acknowledged differences in ribosomal interactions between Gram Positive and Gram Negative bacteria, pointing out specific variations like spacer lengths and 16S rRNA differences.
5. Prof. Salis clarified that the design procedure remains consistent when working with different organisms. However, he stressed the importance of fine-tuning the model for specific organisms, adapting it as necessary.

Our team obtained valuable insights and guidance from Prof. Howard Salis regarding our project. The exchange of emails demonstrated a genuine interest in collaborative learning and knowledge-sharing, illustrating the scientific community's commitment to fostering innovation and progress in the field of synthetic biology.

All-India iGEM Meet

Team iGEM IIT Madras along with teams from other institutes across the country came together at the All India iGEM Meet 2023, held between 28th to 30th July at IISER Bhopal. It was a platform for the teams to exchange ideas, receive feedback and foster collaboration, before the Jamboree.

During the judging session, the teams presented their project ideas and progress. The feedback provided by the judges highlighted areas of improvement and provided guidance for the further course of our project.

A poster presentation and interaction event was organized where the teams discussed their project ideas and experiences. It involved offering suggestions, asking questions, and providing constructive feedback on each other's projects. This exchange of knowledge helped teams to learn from each other's experiences and fostered a collaborative environment, leading to new perspectives and improvements in project design.

During the convention, we had the opportunity to interact with esteemed members of the iGEM community such as Dr. Lavanya Bhagavatula, professor at IISER Bhopal, former Co-PI iGEM IISER Bhopal as well as founder and CEO of Anvaya Biotech, Mr. Jeevan Subodh, iGEM ambassador, Ms Shreya Kulkarni, member of iGEM startups and Ms. Sana Jalili, former judge and iGEM promoter Asia and Oceania 23’.Their invaluable insights and recommendations immensely contributed to the enhancement of our project. One of the suggestions was to include a proof of concept in the project explicitly in order to demonstrate the feasibility and functionality of the project. They also recommended validating our model software by comparing the predictions to actual experimental data from the wet lab.

It was a great networking opportunity, enabling us to build connections with individuals from other institutes and experts in the field, paving way for further collaborations and fostering a sense of community among the iGEM teams.

Meeting Biocon

Biocon, a leading and innovative biopharmaceutical company known for its development of affordable biosimilars, generic formulations, and complex APIs, warmly received our project presentation. During our presentation, we introduced them to our RBS calculator and optimiser software, providing insights into their development, parameter choices, and advantages over existing standards.

We discussed the development process, emphasizing the precision and reliability of our RBS calculator and optimiser software. We also explained the key parameters and algorithms used to fine-tune gene expression, highlighting how our software offers improved control and predictability in bioengineering.

Our presentation showcased how our software surpasses current industry standards, offering a more efficient and streamlined approach to optimising gene expression. This is particularly crucial in biopharmaceutical research and production.

We engaged in a discussion about the potential for advancing our project and collaborating with Biocon for real-world applications, especially due to their research in the field of recombinant proteins like hyaluronidase.

Biocon's representatives expressed their enthusiasm for our project and its potential impact, and they offered to sponsor further research and development efforts to support innovation in the biopharmaceutical industry.

Biocon also extended an invitation to IIT Madras for an industry visit to their headquarters in Bangalore, providing us with an opportunity to witness their research action and explore potential synergies in person.

Distinguished individuals from Biocon, including Dr. Nagaraj, Dr. Krishna Rao Kamisetty, Dr. Naga Sirisha Chalamalasetty, Dr. Ravi Kant Pandey, and Dr. Shivakumar Basavaraju, were present during our presentation, adding significant value to the discussion.

We are eager to work closely with Biocon to formalize our collaboration and continue advancing our project, with the shared goal of driving innovation and excellence in the biopharmaceutical sector.

Conversing with

As part of our efforts in making the tech-bio intersection accessible, iGEM IITM reached out to Manish Sainani, ex–Director of Product Management at Google and founder of In an in-person session, our team laid out our perspective of the synthetic biology landscape, and where we hoped our in-house tools would make a significant impact. As a founder in the tech-AI sphere, Mr. Sainani’s expert opinion on the potential developmental and entrepreneurial pitfalls and opportunities involved in refining and scaling this tool, and broadly exploring the biology-technology intersection was instrumental in redefining our future approach.

A Visit to IITM Research Park

iGEM IIT Madras finds it extremely crucial to align the project’s utility with professional standards. Keeping this in mind, we visited IITM Research Park to get valuable inputs on our project from industry professionals.

A talk on recombinant proteins for food
technology by the Good Food Institute

Using synthetic biology to improve the quality of life and reaching sustainable development goals is the spirit of iGEM. Keeping this goal in mind, we conducted a session with Ms. Chandana Tekkatte, a stem cell biologist from the Good Food Institute.

The meat industry is associated with environmental degradation, animal welfare concerns, and health implications, including antibiotic resistance and increased risk of chronic diseases.Good Food Institute India is a community for entrepreneurs, scientists, students, and subject matter experts who are driving innovation in smart protein. Their aim is to replace meat-derived proteins with sustainable plant based synthetic proteins.

Ms. Chandana Tekkate gave a talk on the importance of recombinant protein technology in the area of food technology which will provide a solution for the food crisis. She walked us through the different methods of producing synthetic edible protein which use plant based sources to make meat-like proteins along with types of fermentation process which are used in the food industry, namely traditional fermentation, biomass fermentation, and precision fermentation.The proteins achieved through these methodologies are called smart proteins.

Advantages and disadvantages of various recombinant protein expression systems were discussed. She emphasized on the importance of choosing the right chassis based on speed, cost, yield, post-translational modifications, process development and scalability regulation approval. After receiving this insightful knowledge from her, we discussed with her the scope of using Lactococcus lactis as an expression system since it is a GRAS organism and has always been used in food technology. She greatly appeciated our initiatives in expanding the genetic engineering toolkit for L. lactis.

Finally the session concluded with an insightful discussion on whether synthetic meat proteins can ever truly replace meat-derived proteins considering the social significance of meat. Even though it may not be widely embraced at the moment, recombinant protein technology seems to be the sustainable solution for an ever rising demand for food proteins.