Human Practices

Human Practices

Every project aims to change the world, but we want the world to change our project, too. The ability to hear the market, people’s needs, and professionals is essential in designing human-centered products. In order to bring a product that finds a place in the world, several feedback loops were created during the whole iGEM cycle. We clustered our stakeholders into 5 main areas: Healthcare, Pharmaceutics, Academia, and Public, which induce the main values that Cellcare is built upon.


Figure 1. Stakeholders-Values Map.


Brainstorming project ideas, our team runs across the idea of therapy via bacteria and the potential of the method with huge room for progress. Brainstorming ideas with researchers at Nazarbayev University, we’ve encountered with research focus of professor Ivan Vorobyev on oncology. Diving into the elaboration of the idea of bacteriotherapy caught us with its novelty along obstacles worthy of a shot. Professor Vorobyov helped us to identify the main limitation in the research and development of current chemotherapy methods is efficiency. So, looking at the ways of enhancing efficiency, we’ve focused on the specificity of Cellcare as the targeting span of chemotherapy is considerably broader. This is how we’ve attained our 1st main value from a Research and Development perspective as - Specificity.

Upon the choice of a particular method with our primary PI, we sought feedback from the pharmaceutical industry in order to find out whether there’s a place for our solution in the industry. In order to understand to what extent our method fits the problems and limitations of current treatment systems, such as availability, side effects, and suitability. We’ve reached out to local and regional manufacturers as well as big pharma representatives in Kazakhstan as AstraZeneca and Merck. Giving a start to the discussion with AstraZeneca Kazakhstan, we’ve set the main trajectory towards which to lead the project. With Zhalgas Daniyarov, public affairs manager at AstraZeneca Kazakhstan, we’ve projected the trajectory on which to lead Cellcare from the stage of initial design to clinical trials. Mr Daniyarov helped us to identify the main limitations of current treatments as affordability. This made us derive our 2nd main value from the pharmaceutical industry to be - availability.


Figure 2. Trajectory towards clinical trials.


We’ve recognized hospitals as not only end-users but valuable stakeholders that shall dictate the way the end product should come out. We were able to establish collaboration with the leading center of the country in the field, the National Research Oncology Center. We were presented with slots to bring up our questions by the end of morning rounds at departments of oncochematology, pathomorphology, and general surgery. Practitioners brought forwards the main limitations of current treatment systems clinical-wise and from a patient’s perspective. So, the side effects of chemotherapy derived our 3rd main value to build upon as biocompatibility to the patient.

Figure 3. 3 R's Cellcare.


Integrated Human Practices


Plasmid Construction


Problem 1. Even though we were aware of the theory behind plasmid and its structure, we lacked a thorough understanding and practical skills for construction.

June, 2023

Darkhan Utepbergenov. | Assistant professor. Department of Chemistry, Nazarbayev University



Alina Saidova. | Our mentor.



As the Biology program at the Undergraduate level does not thoroughly teach how to construct a plasmid. Initially, we planned to construct the plasmid of interest by “cutting” two commercially available plasmids. So we’ve reached out to university labs proficient in the matter and started working with Professor Utepbergenov and Dr. Saidova. They held an internship for the wet lab team with a series of workshops on choosing and ordering a particular plasmid, performing molecular cloning techniques, applying PCR when appropriate, and how a glued plasmid works. It not only taught us practical skills of stepwise plasmid construction but also immensely enhanced our understanding of the concepts that need to be considered while working on a plasmid.

Problem 2. Plasmid Modeling

July, 2023

Ivan Bochkov | Professor. Department of Molecular and Human Genetics, Baylor College of Medicine.



By July, we learned that it’s allowed by iGEM to order an already constructed plasmid. Thus, we started to model the needed plasmid on the software SnapGene and Benchling. Knowledge acquired from the above Problem #1 played a crucial role in building upon modeling the plasmid of interest. We’ve reached out to Professor Bochkov with a research interest in genomics architecture. His experience of working with cancer cells allowed him to give the most competent feedback on the plasmid model. Eventually, we were able to develop the final construct of a pET9a low-copy plasmid, which we later ordered.



Problem 3. Upon completion of the plasmid model, we sought sponsorship to order it.

August, 2023

Bolat Sultankulov | Founder. ARLAN BIOTECH LLP.



A biotech company whose specialisation included work with plasmid in our city was an unexpected surprise. We’ve reached out to Arlan Biotech and pitched the issue to its founder, Bolat Sultankulov. The meeting had a successful outcome, and Mr. Sultankulov agreed to order our plasmid from Genscript and supervise the process, covering all the related expenses. Unfortunately, having ordered the plasmid, we didn’t receive it due to a procedural malfunction at the customs service of Kazakhstan, which put the project on hold. Mr. Sultankulov connected us with an agent who assisted in addressing the questions at customs services, which let us receive the plasmid by the 18th of October.

Nurlybek Mursaliyev | Co-founder of the Biodock

June, 2023

We engaged in a comprehensive discussion with Dr. Mursaliyev covering both the technical and entrepreneurial dimensions of our cancer treatment project. A fundamental lesson emerged from our conversation: the significance of precise presentation and strategic approaches when dealing with sponsors, research grant programs, and potential collaborators or partners. Mr. Mursaliyev provided invaluable insights, stressing the need for a meticulous strategy to navigate these avenues effectively.



Furthermore, our discussion highlighted the necessity of addressing potential technical challenges associated with bacteriotherapy. Specifically, the risk of sepsis due to bacterial intervention and the limitations related to the excessive use of bacteria on a living organism were emphasized. This guidance played a pivotal role in refining our approach, ensuring that we comprehensively addressed these concerns in our project development.



On the entrepreneurial front, Mr. Mursaliyev emphasized the evolving trends in the modern scientific market. He underscored the significance of focusing on therapeutic solutions rather than diagnostic ones, given the existence of similar diagnostic solutions in the market. This strategic insight redirected our focus, aligning our efforts with the changing demands of the industry.



Moreover, in terms of international expansion, Mr. Mursaliyev recommended a targeted approach to entering the USA market. He specifically suggested exploring the NSF i-COPRS program, drawing from his own experience participating in it. His status as a non-resident of the USA made this recommendation particularly relevant, given the challenges we faced in promoting our project in the Western market. This strategic direction provided us with a clear path for our international endeavors, ensuring that we navigated the complexities effectively.



Towards the end of our discussion, Mr. Mursaliyev generously offered his support and personal mentorship for our project. This informal agreement established a channel for us to seek guidance on global project development and other related matters. We mutually agreed to maintain an open line of communication, allowing us to schedule future meetings as questions arose, ensuring the continued progress and refinement of our project.



Ogay Vyacheslav | Managing Director for Science. National Center for Biotechnology

August, 2023

In the meeting with Vyacheslav Ogay, a representative from the National Center for Biotechnology, we delved deep into the intricacies of our project. Mr. Ogay provided valuable insights into the nuances of the scientific market, emphasizing the importance of staying abreast of the latest trends. His guidance underscored the need to focus on therapeutic solutions, an approach that was reaffirmed based on industry demands.



During this meeting, Mr. Ogay reiterated the significance of addressing technical challenges associated with bacteriotherapy. He emphasized the potential risks, especially concerning sepsis, and the limitations linked to the quantity of bacteria used in interventions. This reinforced our understanding of the critical need to develop comprehensive safety protocols and thoroughly evaluate the therapeutic dosage of modified bacteria.



Furthermore, Mr. Ogay provided strategic guidance on project promotion in international markets. He stressed the importance of considering regulatory frameworks, intellectual property rights, and collaborations with local institutions. His insights played a pivotal role in shaping our global expansion strategy, ensuring that we approached each market with a tailored and well-informed perspective.



Our meetings with both Mr. Mursaliyev and Mr. Ogay were instrumental in refining our project's technical and entrepreneurial aspects. Their expertise provided us with a comprehensive understanding of the challenges and opportunities in the scientific market, enabling us to navigate the complexities effectively. Their strategic counsel laid the foundation for our international ventures, setting us on a path toward impactful and responsible global expansion.

Patient Oriented Design


The skills and experience of the team have been improved through iGEM NU Kazakhstan's strong connections with pharmaceutical companies and industry professionals, such as AstraZeneca. AstraZeneca's Zhalgas Daniyarov was a key participant, offering insightful input in several sessions to improve the project and create moral standards.

Zhalgas Daniyarov | Public Affairs Manager. AstraZeneca.

June, 2023

In one of the first meetings, ethics took center stage, with a focus on the moral implications of scientific endeavours. Zhalgas emphasised transparent communication and ethical research practices, laying the foundation for the team's Human Practices component. This emphasis on ethics influenced the team's approach, ensuring compliance with the strictest ethical standards.

July, 2023

The second time, the discussions provided insights into effective communication, enabling the team to articulate their research clearly to scientists and stakeholders. Zhalgas' recommendations emphasized the importance of transparency, fostering open communication and collaboration among team members and stakeholders.



September, 2023

Last time, when we conducted a meeting with Zhalgas Daniyarov, the discussions delved into the complexities of clinical trials, which are essential for the project's progress. The team also explored entrepreneurial aspects, leading to the idea of establishing an R&D firm based on their innovative concept. Commercialization strategies were discussed, broadening the team's perspective and equipping them with skills to transform theoretical ideas into practical, commercially viable solutions.



The conversations we had with the manager of AstraZeneca in Kazakhstan were life-changing. They contributed crucial information and abilities, reinforced the team's ethical basis, and gave strategic ideas. Equipped with this acquired knowledge, the group was more capable of negotiating the complex terrain of science, morality, and business. Through their iGEM project, these experiences enabled them to make a substantial contribution to cancer research.

Problem 1. Difficulties with a method of protein purifying.

June, 2023

Darkhan Utepbergenov | Assistant Professor. Department of Chemistry, Nazarbayev University.



In our collaborative effort to advance our cancer treatment project, we had the privilege of consulting with Professor Darkhan Utepbergenov. Initially, our team had planned to produce two plasmids and conduct a double transformation. However, Professor Utepbergenov, with his vast expertise in molecular biology, meticulously reviewed our initial design and provided invaluable insights that led to a significant refinement of our experimental approach.



During our meeting, Professor Utepbergenov not only shared his extensive knowledge but also generously provided us with essential reagents crucial for our experiments. His guidance extended to the purification process of the protein, where he suggested a method that promised enhanced efficiency and purity. His contributions not only streamlined our experimental setup but also significantly improved the quality of our research.



The collaborative spirit and expertise demonstrated by Professor Utepbergenov were pivotal, laying a robust foundation for the experimental phase of our project.



Hydrogel Design


Problem 1. Potential toxicity of hydrogel to bacteria

June, 2023

Mannix Balanay | Assistant Professor. Department of Chemistry, Nazarbayev University.



The expertise of Professor Ellina Mun in chemistry and pharmacology made us collaborate with her as a secondary PI. She led our team in constructing hydrogel matrix sharing, explaining the choice of the primary polymer, methods of synthesis, and essential qualities of components to consider. Upon making the 1st hydrogel gel, we sought additional feedback and reached out to Professor Mannix Balanay, whose research interest covers physical and materials chemistry. Sharing a profound interest in the project, he addressed our concern about the compatibility of hydrogel composition with bacteria. From articles, we derived that chitosan is a toxic environment to bacteria cells and may kill them while encapsulating. Professor Balanay suggested running an MTT Assay experiment to check it. We’ve learned from the results that chitosan induces low toxicity to the bacteria cells.



Problem 2. Immune response to the hydrogel system

July, 2023

Gonzalo Hap Hortelano | Dean. Department of Biological Sciences, Nazarbayev University.



In order to understand the immunity response once the system is injected into the organism, we’ve reached out to Professor Hortelano, who has expertise in Immunology. The professor pointed out that although the bacteria is wrapped in hydrogel, partial leakage would occur. He suggested adding a kill switch into the plasmid in order to kill bacteria in particular conditions. However, we warned that it would, in turn, make the plasmid considerably more significant in size, which would decrease the rate of bacterial transformation. So, in response, he offered to treat bacteria leaked from the hydrogel coat, prescribing patients antibiotics.



Safety and Usability of CellCare


Meeting agenda. Side effects of current cancer treatment methods and safety aspects of CellCare.

June, 2023

Anna Midlenko | Surgical Oncologist. National Research Oncology Center.



Our discussion with Anna Midlenko, a representative from the National Research Oncology Center, shed light on the critical issue of safety and usability in cancer treatments. Anna Midlenko highlighted the alarming fact that only two existing types of chemotherapy for treating solid tumors are currently in use, both of which have harmful effects on the human body. In light of this, our novel approach, combining hydrogel with modified bacteria, offered a promising alternative.



Anna Midlenko provided valuable feedback on the safety and usability aspects of our model. Her insights helped us refine our understanding of the potential risks associated with the treatment and encouraged us to further bolster safety protocols. Her perspective underscored the urgency of our research, emphasizing the need for innovative, safer alternatives to existing treatments.



Meeting agenda. Integrating CellCare model with current cancer treatment methods.

August, 2023

Dmitry Guschin | Assistant Professor. Nazarbayev University School of Medicine.



In our meeting with Dmitry Guschin, a respected oncologist, we had the opportunity to discuss our innovative cancer treatment model, combining hydrogel with modified bacteria. Dr. Guschin provided insightful feedback, emphasizing the importance of integration with existing cancer treatment methods. He pointed out that our unique approach could be further optimized by combining it with established treatment models, enhancing its effectiveness and widening its applicability. Dr. Guschin’s advice illuminated a path forward, showing us how our novel method could be seamlessly integrated into the existing landscape of cancer treatments.



Patient Oriented Design


The skills and experience of the team have been improved through iGEM NU Kazakhstan's strong connections with pharmaceutical companies and industry professionals, such as AstraZeneca. AstraZeneca's Zhalgas Daniyarov was a key participant, offering insightful input in several sessions to improve the project and create moral standards.

Zhalgas Daniyarov | Public Affairs Manager. AstraZeneca.

June, 2023

In one of the first meetings, ethics took center stage, with a focus on the moral implications of scientific endeavours. Zhalgas emphasised transparent communication and ethical research practices, laying the foundation for the team's Human Practices component. This emphasis on ethics influenced the team's approach, ensuring compliance with the strictest ethical standards.

July, 2023

The second time, the discussions provided insights into effective communication, enabling the team to articulate their research clearly to scientists and stakeholders. Zhalgas' recommendations emphasized the importance of transparency, fostering open communication and collaboration among team members and stakeholders.



September, 2023

Last time, when we conducted a meeting with Zhalgas Daniyarov, the discussions delved into the complexities of clinical trials, which are essential for the project's progress. The team also explored entrepreneurial aspects, leading to the idea of establishing an R&D firm based on their innovative concept. Commercialization strategies were discussed, broadening the team's perspective and equipping them with skills to transform theoretical ideas into practical, commercially viable solutions.



The conversations we had with the manager of AstraZeneca in Kazakhstan were life-changing. They contributed crucial information and abilities, reinforced the team's ethical basis, and gave strategic ideas. Equipped with this acquired knowledge, the group was more capable of negotiating the complex terrain of science, morality, and business. Through their iGEM project, these experiences enabled them to make a substantial contribution to cancer research.

Relevance and Positioning of CellCare


Nurlybek Mursaliyev | Co-founder of the Biodock

June, 2023

We engaged in a comprehensive discussion with Dr. Mursaliyev covering both the technical and entrepreneurial dimensions of our cancer treatment project. A fundamental lesson emerged from our conversation: the significance of precise presentation and strategic approaches when dealing with sponsors, research grant programs, and potential collaborators or partners. Mr. Mursaliyev provided invaluable insights, stressing the need for a meticulous strategy to navigate these avenues effectively.



Furthermore, our discussion highlighted the necessity of addressing potential technical challenges associated with bacteriotherapy. Specifically, the risk of sepsis due to bacterial intervention and the limitations related to the excessive use of bacteria on a living organism were emphasized. This guidance played a pivotal role in refining our approach, ensuring that we comprehensively addressed these concerns in our project development.



On the entrepreneurial front, Mr. Mursaliyev emphasized the evolving trends in the modern scientific market. He underscored the significance of focusing on therapeutic solutions rather than diagnostic ones, given the existence of similar diagnostic solutions in the market. This strategic insight redirected our focus, aligning our efforts with the changing demands of the industry.



Moreover, in terms of international expansion, Mr. Mursaliyev recommended a targeted approach to entering the USA market. He specifically suggested exploring the NSF i-COPRS program, drawing from his own experience participating in it. His status as a non-resident of the USA made this recommendation particularly relevant, given the challenges we faced in promoting our project in the Western market. This strategic direction provided us with a clear path for our international endeavors, ensuring that we navigated the complexities effectively.



Towards the end of our discussion, Mr. Mursaliyev generously offered his support and personal mentorship for our project. This informal agreement established a channel for us to seek guidance on global project development and other related matters. We mutually agreed to maintain an open line of communication, allowing us to schedule future meetings as questions arose, ensuring the continued progress and refinement of our project.



Ogay Vyacheslav | Managing Director for Science. National Center for Biotechnology

August, 2023

In the meeting with Vyacheslav Ogay, a representative from the National Center for Biotechnology, we delved deep into the intricacies of our project. Mr. Ogay provided valuable insights into the nuances of the scientific market, emphasizing the importance of staying abreast of the latest trends. His guidance underscored the need to focus on therapeutic solutions, an approach that was reaffirmed based on industry demands.



During this meeting, Mr. Ogay reiterated the significance of addressing technical challenges associated with bacteriotherapy. He emphasized the potential risks, especially concerning sepsis, and the limitations linked to the quantity of bacteria used in interventions. This reinforced our understanding of the critical need to develop comprehensive safety protocols and thoroughly evaluate the therapeutic dosage of modified bacteria.



Furthermore, Mr. Ogay provided strategic guidance on project promotion in international markets. He stressed the importance of considering regulatory frameworks, intellectual property rights, and collaborations with local institutions. His insights played a pivotal role in shaping our global expansion strategy, ensuring that we approached each market with a tailored and well-informed perspective.



Our meetings with both Mr. Mursaliyev and Mr. Ogay were instrumental in refining our project's technical and entrepreneurial aspects. Their expertise provided us with a comprehensive understanding of the challenges and opportunities in the scientific market, enabling us to navigate the complexities effectively. Their strategic counsel laid the foundation for our international ventures, setting us on a path toward impactful and responsible global expansion.

Survey


In order to estimate the level of cancer awareness among the local population and evaluate the overall education regarding cancer treatment methods our team decided to make a survey dedicated for knowledge estimation of the public. The survey was taken during our initial events and gathered 127 answers.

The results are following:

Figure 4. Survey Results.


Thus from the results of the survey we deducted following problems:

1) Low Awareness of Cancer Immunology

According to the results obtained it was identified that people have quite an understanding that the immune system has an ability to fight cancer, however, only around 35% of the respondents know that cancer cells are neglected by the immune system due to their mutation that allows them to be undetectable. These results represent that people have a vague understanding of the immune system’s role and its connection to cancer treatment.

2) Limited Awareness of Cancer Treatment Options

Moreover, 83.1% of respondents chose chemotherapy as a familiar treatment type, which is obvious and could be comprehended since it is the most common and traditional cancer treatment method nowadays. The rest choose radiotherapy as another method. Hence, people do not really know about any other novel possible treatment methods such as immunotherapy, bacteriotherapy etc.

3) Low Perception of Treatment Effectiveness

As for rating effectiveness of modern cancer therapies on average respondents gave grade 5 out of 10. People tend not to believe in the efficiency of novel cancer treatments.

4) Lack of Believe in Cancer Vaccines and Treatments Free From Side Effect

More than half (58.4%) of the respondents do not believe that there is a vaccine against cancer and that there is a possibility to treat cancer without any side effects.

5) Inadequate Education and Awareness

On top of that, the same amount of people did not get any training on cancer prevention and on the importance of oncomarker check ups.

By identifying these problems we thought that the best way to contribute is raising people’s awareness through the distribution of information with the help of various fascinating events. So the survey shaped our scope of the events to be conducted. Making events interesting and interactive attracts more attention from the people and thus more people may be involved in the problem of cancer education that we tried to share with the public. The organisation of the major events of our team like Summer Camp, Blood Donation Day and BioArt exhibition helped us to convey the message of the significance of raising cancer awareness among local people. Furthermore, social media was a great tool that helped us to share the information with the public.

We are highly dedicated in developing a philosophy of prevention of cancer amongst local folk apart from developing a drug, Cellcare. Our prime aim of working with the public has been transmission of values. The survey did not help us only to recognize the major problems of our society in the context of cancer awareness, however it also contributed to the evolution of CellCare as we used the feedback of the people taken from the surveys and tried to integrate it into our project.