1. Contribution - Our goals

Blending Traditional Chinese and Western Medicine to fight lung cancer

We would like to explore the potential of Cordyceps militaris peptides against Non-Small Cell Lung Cancer (NSCLC). Four peptides from Cordyceps militaris, a well-known dietary therapy in anticancer treatment, were selected to test their effectiveness to lung cancer. Also, we modified those peptides by adding linker and cell-penetrating peptide.


Providing alternative pathway for treating lung cancer, combining AI peptide with Cisplatin

We aim to merge the old and new methods of treating lung cancer, with the former being chemotherapy drugs, and the latter, AI-generated peptides that cannot be found in nature. With any luck, this will lead to better lung cancer treatment options and a decrease in the side effects that patients endure from chemotherapy. Consequently, helping the medical community with the battle against lung cancer.


Reducing the dosage & thus the side-effects of Cisplatin

Due to the unbearable side effects, it was seen that some patients did not complete their course of chemotherapy. Combining the AI-generated peptides with chemotherapy allows for a reduction in the dosage of the drug (cisplatin), which minimizes side effects. Patients can now continue their treatment without experiencing any discomfort.

It is likely that other iGEM teams and researchers will also explore this topic. To support these efforts, we have made all detailed information regarding our project available, with the aim of facilitating further research and collaboration in this area.


2. Part contribution: Anticancer peptides

Our project aims to design and produce an ACP which can have combination effects with cisplatin against Non-Small Cell Lung Cancer (NSCLC). In order to contribute to the iGEM community, we uploaded the plasmid design and experimental steps related to these anticancer peptides on the wiki page. This information is available for other iGEM teams working on projects related to anticancer peptides. They are welcome to view the wiki page to gain insights into our experiments if needed.

We made contributions to the part registry by uploading information regarding expressing anticancer peptides. We have designed fifteen BioBrick™ parts to express different anticancer peptides in our expression system. AC-P19 is an anticancer peptide which has been experimentally proved to have anticancer ability against the A549 cell line [BBa_5056009]. We used it as a positive control. Four peptides from Cordyceps militaris, a well-known dietary therapy in anticancer treatment, were selected to test their effectiveness against lung cancer [BBa_5056005]-[BBa_5056008]. We also modified these five peptides (AC-P19, C-ori, C-rds, CTP-ori, and CTP-rds) by adding a linker and cell-penetrating peptide to increase anticancer ability via promoting cell-penetrating ability [BBa_5056011]-[BBa_5056015]. Furthermore, we used RFdiffusion and ProteinMPNN-AI to generate all-new peptide sequences by targeting PDEδ, which regulates KRAS signaling, a common gene mutation in cancerous cells. Linker and cell-penetrating peptide are also added at the end of these de novo peptides to increase their cell-penetrating ability [BBa_5056000]-[BBa_5056004].

Below are the parts numbers:


3. Modeling contribution: All new anticancer peptides

We identified the 4JV6 structure of PDEδ and then targeted three hotspot residues that our de novo peptides could bind to, changing the shape of PDEδ and preventing it from interacting with KRAS. In order to do that, three artificial intelligences were utilized to generate 16 de novo peptides—which are not found in nature—on cell line A549 and selected five of them (higher score) for wet lab testing. RFdiffusion (which generated backbones), ProteinMPNN (which generated backbone sequences), and AlphaFold (which screened peptides and predicted the outcome of our KAPI and PDEδ). For more information, please visit our modeling part.


4. Education contribution: Promoting synthetic biology in different ways

Publications

To provide students with a basic knowledge of biology. Our team made a leaflet, booklet, and pamphlet for kindergarten, primary, and secondary students, accordingly. Each edition includes additional information about our research as well as advanced lab experiment procedures, including cell passaging, cytotoxicity testing, and AI modeling. We intend to spark children's interest in synthetic biology by teaching them fundamental biology concepts, as well as to increase students' grasp of the topic and enrich their learning experience. In turn, students are inspired to become biologists in the future.

Fig. 1: Pictures of booklet

Newsletter, picture book, card game and board game

Moreover, our team has been publishing a newsletter every month called the HK-Joint-School iGEM Newsletter. This interschool publication is distributed to students from all participating schools. The newsletter highlights our team's progress, educates readers about synthetic biology, and provides information on iGEM activities. In order to reach a wider audience, we designed a picture book for students in kindergarten all over Hong Kong to arouse interest in biology, life science, and biotechnology. Our team seized advantage of this opportunity to spread awareness about lung cancer and provide them with innovative usages of biotechnology. Our team aims to raise awareness about lung cancer. A board game named “Lung Story Short!” and Card game (PokeACPs – The Cancer Killer) are therefore designed during the research project. They will be shared with the public..

Fig. 2: Pictures of newsletter, 'Lung' Story Short boardgame and Card game (PokeACPs – The Cancer Killer)

After that, our team planned a Kahoot and board game tournament for the BLMCSS students. The game "Lung Story Short!" attracted 25 participants from Grades 7-9 (i.e., junior form students). Competitors eagerly engaged in the event, demonstrating their passion for science and technology.

Workshops and assemblies

We organized a great quantity of high-quality workshops for people of all ages in order to educate them about our research and expose them to synthetic biology. Serving them with compassion, we have effectively educated over 3000 individuals via over 20 programs. We also hosted multiple assemblies at several schools, including BLMCSS and HPCCSS, to encourage students to seek careers in scientific research through our project. We believe that by introducing iGEM, we can recruit future iGEMers for next year's competition.

Fig. 3: Educating different age group with our project and introduce synthetic biology

Fig. 4: Several assemblies in different schools such as BLMCSS and HPCCSS

Google Forms, surveys and social media promotion

To teach students more about synthetic biology and biotechnology, our team created reading-to-learn Google Forms for various students. These Google Forms cover a variety of themes, including cancer clinical treatments and scientific advancements in cancer cures in China. Finally, increasing students understanding of such things.Student questionnaires were also designed to improve awareness of lung cancer.

Fig. 5: Google forms and surveys targeting different students

We organized an Instagram account, introducing our project and educating people with it. We also shared our progress, such as the interviews we did and some of the workshops we have organized. Moreover, we created funny reels on Instagram introducing some wet lab works, aiming to educate them on some of the basic laboratory safety precautions and some basic tools and techniques used in the wet

Fig. 6: Our Instagram account

We organized a YouTube account, sharing our process of doing cancer cell culture. With a series of 8 episodes, we shared the scientific concepts in an entertaining way to educate the public.

Fig. 7: Our Youtube account

For more information, please visit our education part.https://2024.igem.wiki/hk-joint-school/education