Introduction
Our team was influenced by the difficulties patients with rare cancers face, as far as the treatment is considered: existing chemotherapies as well as radiotherapies can be a “harsh” treatment scheme. We believe that “humans generate science for humans”, so a researcher’s work should be adapted to society’s needs. Rare cancers are unfortunately usually not under the spotlight, due to the low percentage of patients suffering from them. We believe that all patients should have equal opportunities for health, especially when the latest treatments can be precise.
We tried to reach out to patients and medical experts to recognize their needs, and shape our project according to them. We also connected with professors, who were experts on the methodology of certain parts of our project such as the molecular mechanism, nanocarrier, experimental procedures and bioethics. Associations, companies, institutions and regulatory bodies were important during our project development, since their advice, feedback and opinion shaped our approach to Theriac implementation. These meetings aimed to form our project into an innovative and realistically implemented theranostic approach for glioblastoma.
We did not promise to change the world, but we are dedicated to trying to!
Human Practices
Associations
Give Hope ELPIDA
In our effort to get in touch with cancer specialists at TIF HELEXPO, we visited the
ELPIDA Association. “ELPIDA” is a non-profit organisation that implements an integrated framework of care and support for children suffering from cancer and their families, raising awareness. We had the chance to discuss with representatives the difficulty of treating glioblastoma cancer in Greece, the limited access of GBM patients to healthcare, and the serious side effects of available treatment. We also talked about the future implementation of our project and the difficulties we may face to bring Theriac to the market. Trying to raise awareness of rare cancers and cancer in general, we decided to become volunteer bone marrow donors, by just giving a saliva sample. We hope no one has to undergo a transplant procedure, but if they do, and we can, we'll be there to help.
Medical Experts
Georgios Papazisis
Georgios Papazisis MD, Ph.D., is an Associate Professor of Basic and Clinical Pharmacology at the School of Medicine of the AUTh. His interests include clinical Neuropsychopharmacology and adverse drug reactions. We approached him because he currently serves as an External Expert for the European Medicines Agency (EMA) and is also National Representative Observer of the EMA Central Nervous System Working Party. He is an external expert and clinical assessor for the Pharmacovigilance Department of the Greek National Organization for Medicines (EOF) and a member of EOF’s Second Degree Scientific Advisory Board. Dr. Papazisis explained the process needed for developing a new therapy from the discovery and development stage to the preclinical trials and later the clinical. His insights helped a lot with our business model. Regarding the safety part of our project, he highlighted the importance of our nanocarrier to be able to penetrate the BBB to achieve brain clearance and avoid toxicity.
Yasmine Chemrouk & Sophie Lantheaume
Dr. Yasmine Chemrouk and Dr. Sophie Lantheaume are expert psychologists from France who work with cancer patients. Our kind partner, iGEM Toulouse connected us to both of them, taking on both the initial approach and also the translation where needed. A consideration crucial for our project is the quality of life of glioblastoma patients. The quality of life index includes among others, our mental health. Patients can “oscillate in these periods between moments of hope on the one hand and despair on the other. During these periods, there is questioning, life reviews sometimes, mourning and a desire to accomplish certain things before dying”, says Dr. Sophie. Both experts gave us clear insights into the psyche of cancer patients, how to help them when they have to make important, informed decisions about their life or their choice of treatment and how to advise or help their family. This opportunity offered us a better scope into fundamental psychology and medical ethics necessary for any scientist in the field of cancer therapeutics.
Professors
Fok Kin Lam Ellis
Prof. Fok K.L. is a professor of Biomedical Sciences in Hong Kong- SBS with years of experience in teaching RNA interference. The reason we met with him was to hear his expert advice on the siRNAs we choose, the unwanted systemic effects they might have, the functionality of our molecular mechanism, and the systemic distribution of our molecules. He suggested we check that there are no cleavage points on our hairpin structures that would cause the unwanted release of our nanocarrier.He said it is a big goal to achieve and that our approach is pretty interesting. We are very grateful to
iGEM CUHK-HongKong-SBS for arranging this meeting.
Panagiotis Bamidis
Panagiotis Bamidis is a Professor of Medical Physics, Informatics and Medical Education and Director of the Lab of Medical Physics and Digital Innovation in the School of Medicine of AUTh, Greece. His research is about understanding the brain’s reaction to different stimuli, technological or educational interventions, the development and evolution of human emotions and sleep transitions. He is the President of the Hellenic Biomedical Technology Society (ELEBIT), HL7 Hellas, the International Society of Applied Neuroscience (SAN), and a member of the Administration Boards of other societies and patient associations. We presented to him our ideas while we still hadn’t decided that our project would be about glioblastoma cancer. He liked our innovative ideas and talked to us about the technologies in neuroscience, and our interest in brain cancer increased.
George Mosialos
He is a professor at the Department of Genetics, Development and Molecular Biology, in Aristotle University of Thessaloniki and he is a former professor of Medical School of Harvard, in the department of microbiology and immunology. We had a meeting with him, to discuss the details about the molecular aspect of our project. We gave us very useful advice on Theriac mechanism testing in the lab.
Vasiliki Fadouloglou
Vasiliki Fadouloglou is an assistant professor at the Department of Molecular Biology and Genetics, of Democritus University of Thrace. Her interests include structural biology, protein chemistry, enzyme catalysis and non-coding RNAs. We had a meeting to present our project and talked about the stability of the molecules we were about to design using Nupack. Our team had questions about the use of this program and if it was useful for the data we wanted to process. Professor Fadouloglou encouraged us to use Nupack to design our project’s hairpins and clarified that this program is for the secondary structures of our molecules.
Iro Koliakou
Dr. Iro Koliakou is a physics teacher and the coordinator of STEM at Anatolia College. She was awarded the “Global Teacher Award 2021” by the AKS organisation for her inspiring and creative teaching work. She coordinates two European projects, “Green Education for a Sustainable Future” and “Mini Open Labs”, which promote STEM and green education in Europe. She is an ambassador of the European team “Scientix”, which is a teacher’s team in STEM. Iro Koliakou is a founding member of the European Association of STEAM Educators and a member of Stage Europe, developing STEM activities related to the 17 Sustainable Development Goals of the United Nations. She is also a member of Greek Women in STEM, Real Science, and Global Talent Mentoring.
She really helped us to organise our educational plans and school visits and supervised the content shared. Her guidance was valuable and decisive for our educational plans, and we thank her from the bottom of our hearts.
Ioannis Lykakis
Ioannis Lykakis is an Associate Professor at the Organic Chemistry Laboratory, of Chemistry School, A.U.Th. His research interests include Catalysis and Photocatalysis of Organic Reactions in the context of Sustainable Chemistry, with the use of metal nanoparticles and polyoxometallic clusters, as well as the development and mechanistic study of new catalytic synthetic methodologies for the production of organic compounds with possible biological interest.
We had meetings presenting our project and discussing possible experimental methodologies we could use. He pointed out that we should take into consideration while designing our project, the acidic pH levels of the cancer cells. Also, he proposed doing an experiment using Nuclear Magnetic Resonance spectroscopy to determine the molecular structure and chemical composition of our samples in order to check the hybridization reactions.
Stavroula Tsinorema
On the 3rd of August, our team and our partners, iGEM Crete, had an online meeting with Ms. Stavroula Tsinorema, Professor of Modern and Newer Philosophy and Bioethics. We discussed the necessity of bioethics and the ways to promote it but also to pursue it individually. We addressed the bioethics of Theriac and Atropa (iGEM Crete's project). Regarding the implementation of Theriac, Mrs. Tsinorema pointed out the necessity to examine the experimental rules at the stage of clinical trials.
She emphasized that living organisms are a part of this process, for which special permits are required and their handling must conform to the laws. At the stage of clinical trials in humans, the application of bioethical protocols is a prerequisite for them to start. Specifically, because Theriac targets cancer cells in the brain, perhaps the most precious and sensitive organ, it is necessary to strictly follow the safety protocols. She suggested that the siRNAs interfere only in one biochemical pathway that it’s not activated in healthy cells so the appearance of unwanted energies will be prevented. She gave us food for thought regarding the conduction of Theriac’s clinical trials, which we considered during our entrepreneurship plan. Moreover, she underlined the dire need for the existence of ethical behavior by each scientist so that the implementation of each work does not raise questions of a moral nature.
Theodora Choli-Papadopoulou
Theodora Choli-Papadopoulou is a professor of biochemistry at the School of Chemistry at the Aristotle University of Thessaloniki. Her research interests focus on nanotechnology in the field of synthetic biology and biomaterials. We had a meeting with her when still our potential projects were a lot and we hadn’t decided on Theriac. After presenting all of our ideas, she encouraged us to choose for our project the molecular mechanism of Hybridisation Chain Reaction (HCR), since she thought it was really innovative and interesting.
Other
Beetroot
Beetroot is a graphic design company, which helps with branding, web design and development, advertising, identity and even more! We visited their department in Thessaloniki, and showed them how we present our team, our project during presentations at conferences, scientific symposiums and engagement on social media. We gained useful feedback on how to approach our team’s promotion and our project’s presentation. They also inspired us to take into account the web accessibility guidelines for our wiki!
Integrated Human Practices
Associations
Cancer Association of Macedonia and Thrace
Realistically and statistically speaking, if Theriac makes it into the market it will take years. Nevertheless, we consider the opinion of the end user vital for the future implementation of Theriac. Thus, we visited the Cancer Association of Macedonia and Thrace and met with members who were cancer patients and survivors. At our meeting, we explained to them our project, future goals and vision. Their experience and the difficulties they faced regarding accessibility to healthcare, side effects and psychological issues, gave us the motivation to deal with rare cancer and take Theriac one step further. The main focus of our meeting was the best practices to establish truthful and meaningful communication. How to explain our project and future goals without making any promises.
Regarding Theriac’s future implementation, most of the patients stated that while they prefer less invasive methods of administration, they feel insecure without the surgery. Nevertheless, they found our proposal for intranasal administration very innovative because as they mentioned during chemotherapy their veins are getting destroyed and administration is difficult and painful. They also stated the importance of fewer side effects in combination with increased efficacy. We took all of their feedback under serious consideration while searching for the implementation of our project. Thus, we decided to proceed with intranasal administration and ensured that Theriac will work as intended even after surgery.
Medical Experts
Nikolaos Foroglou
Dr. Nikolaos Foroglou is a member of the Education Committee of the Hellenic Neurosurgical Society, a member of the Administrative Council and a former President of the National Neurosurgical Society. We talked to him over several meetings to answer questions and get feedback on our strategy for reviewing papers for biomarkers selection. His insights into the pathology of GBM were crucial. He highlighted the difficulties that the medical community is facing with GBM therapy and patient monitoring. The literature review and the data analysis indicated miR-21, miR-20a, miR-10b, and miR-155 as the best candidates. Dr. Foroglou guided us in the final selection, suggesting that we should target one overexpressed and well-studied microRNA in glioblastoma (miR-21) and one highly specific for glioblastoma cells (miR-10b).
Nikolaos Papanikolaou
Dr. Nikolaos Papanikolaou is an experienced researcher with a demonstrated history of working in the higher education industry, skilled in Radiomics, Machine Learning, AI, Imaging Biomarkers, MRI, and Oncology. He looked over our project and made a couple of important corrections and suggestions. In practice, convolutional neural networks are mighty in detection and segmentation but therein lies the problem of overfitting. He mentioned that to do what we want, we need thousands of patients so that it doesn't happen. There are differences among the images when they come from different machines and hospitals, and MRI scanner is not like the blood pressure monitor. That is why we must have a very large sample so that the algorithm has seen almost all of the differences possible. Otherwise, we could come up with something that works with a specific protocol on a specific machine. He also confirmed that necrosis is visible on MRI, so we implemented that in our software, targeting necrosis as one of the desired output percentages. To sum up, his advice was that radiomics is the only available option for what we want, with the best suggestion being the use of deep learning. That’s how our software was born!
Professors
George Malliaras
George Malliaras is Prince Philip Professor of Technology at Department of Engineering, University of Cambridge. His research is on bioelectronics and he is the leader of a group of scientists, engineers, and clinicians who develop better tools for healthcare. His research also includes bioelectronics with applications on neurological disorders and brain cancer. He is also a Fellow of the Materials Research Society and of the Royal Society of Chemistry while serving as a Deputy Editor of Science Advances and being the Director of the EPSRC IRC in Targeted Delivery for Hard-to-Treat Cancers. Our team was interested in creating a hardware tool as quality control for our wet lab experiments. We were looking for a cost-effective alternative technique to monitor the reaction of our hairpins. Searching through the literature, we found various techniques and materials to use in microelectrodes. Thus, we had a meeting with professor Malliaras. He encouraged us to proceed with the use of microelectrodes for our project. He specifically suggested using gold microelectrodes instead of other materials, he shared his protocols and warned us that microelectrodes can’t be reused.
George Komis
George Komis is an Associate Professor, at the School of Biology at Aristotle University of Thessaloniki. His research interests include plant Biology, physiology, genetics, molecular biology, and even more. He is in charge of the confocal laser scanning microscope at the School of Biology. We approached him because we wanted to include the confocal laser scanning microscopy in our project. However, our collaboration was more just a protocol for confocal microscopy. We were looking for a way to monitor the release of the siRNAs from our hairpins. He suggested adding a fluorochrome to the end of our HCR-hairpins and a quencer to the siRNAs. We were worried that this might change the secondary structure of our hairpins, thus Dr. Komis helped us choose the most appropriate fluorochrome (ATTO 633) and quencer (BHQ3). His advice definitely affected our measurements in a positive way.
Mavroeidis Angelakeris
Mavroeidis Angelakeris is a Professor at the Department of Solid State Physics of School of Physics in the Faculty of Sciences, A.U.Th. His scientific expertise include, the synthesis of metallic, magnetic, and semiconductor thin films, multilayers and nanoparticles. He also focuses on biomagnetism applicability mostly on Magnetic Particle Hyperthermia and Magneto Mechanical Stress. Our first meeting was on 25/02/2022, and we talked about the application of nanocarriers in biotechnology and how a DNA system could be carried by them. He suggested using magnetic nanocarriers, since they are easier to monitor due to their magnetic properties and commented that their cytotoxicity could be controlled via the concentrations used and probably with a proper coating. After our meeting, during our bibliographic research, our team focused on magnetic nanoparticles for Theriac’s implementation, both for transfer and MRI signal amplification.
Pharmaceutical Companies
Novartis, Kyriaki Antoniadou
We had a meeting with Kyriaki Antoniadou, the Precision Oncology Lead at SERCE & Greece at Novartis Oncology. She is an experienced professional in medical and commercial management. She has been working for over 15 years in multinational pharmaceutical companies and collaborates with medical professionals and stakeholders in the healthcare. She is an expert in personalised medicine, as far as the formulation and execution of commercial and marketing strategies are considered. During our meeting, we talked over some parts of our project mainly focusing on its implementation. We shared some ideas for the administration of Theriac, including the one we prefer (intranasal). She helped us strengthen our hypothesis that intranasal administration might be better, analysing the reasons why it would also help the future implementation of Theriac. ‘’It is quite an innovative project, and administration through the nose would be helpful for the production of Theriac, from pharmaceutical companies.’’
Entrepreneurship
WEP Women Entrepreneurship Platform
WEP is an international non-profit organisation based in Brussels, Belgium, which promotes, supports and advocates on behalf of women entrepreneurs as an official European body. The goal is that by 2030, women will be 50% of entrepreneurs in Europe, while at the same time it promotes and improves access to finance, education, innovation, government policies and networks.
We had a meeting with Lina Tsaltampasi, who is the president of the Greek Association of Women Entrepreneurs and CEO of OECON Group of Companies, which “converts ideas to reality”, by providing Business Development Consulting Services about a wide range of activities of companies. During our meeting we discussed the future implementation of our project, how it could realistically be implemented, what steps we should follow to form our business model canvas and future funding. She also provided us with a letter of support for our entrepreneurship plan.
Rhoé company
For the implementation of our entrepreneurship plan we came in contact with Theocharis Vlachopanagiotis, CEO of Rhoe - a multiple award-winning green mobility startup. He co-founded Rhoé when still an undergraduate student in the Aristotle University of Thessaloniki. He is a member of Sigma Square Society, a Global Student Entrepreneur winner and a mentor for Vodafone's Generation Next program. Both Mr. Vlachopanagiotis and his colleague Giannis Ouranos (project manager) helped us with our entrepreneurship plan. The logistics of a startup that has to pass its product through clinical trials did not make sense. Thus, they suggested building a business model around a platform for NFTs to support funding research. More on our entrepreneurship page.
