Let me walk you through my idea for this contest! It's probably something you haven't heard of before but it's definitely a field which requires more admiration and support! It's called Oncolytic Virotherapy! It is genetically modifying a virus and creating such a virus that can only attack cancer cells while sparing healthy cells. This type of virotherapy utilizes cellular vehicles called liposomes to deliver the viral particle effectively. This virus mainly focuses on lysis of Lung and Pancreatic Cancer using the Monoclonal antibodies and BiTEs that specifically bind to Epidermal Growth Factor Receptors (EGFRs) that are excessively expressed in Lung and Pancreatic Cancer cells. The stable genes can be incorporated with lower chances of immune suppression than other oncolytic viruses and low pathogenicity for normal cells. Selected genes may be deleted or inserted to gain therapeutic effects and evade the immune system till they successfully reach the tumour cells. After this, the virus uses the tumour’s cellular machinery to replicate. This replication culminates with the cell bursting (lysis). The death of the tumour cells and release of antigens stimulate an immune response. This results in the recruitment of immune cells (T, NK and Dendritic cells) then successfully enter the Tumour Micro-Environment (TME) and attack the remaining tumour cells. Present Oncolytic Virotherapy faces several challenges: lowering toxicity to normal cells, tumour heterogeneity, proper delivery etc. Combating these challenges through a blend of unique approaches like using monoclonal antibodies (mAbs) and Bispecific T-cell Engager (BiTE) to create a synergistic treatment for Cancer proved to be successful through this study. By far, Lung and Pancreatic Cancer cells are the most challenging types of Cancer to kill mainly because of their immunosuppressive Tumour Micro-Environment (TME), high resistance to chemotherapy and their surgical operations are quite complex due to their anatomical location and positioning near vital blood vessels. Only a small percentage of patients (around 15-20%) are eligible for surgery at diagnosis due to the extent of the disease. The standard procedure, the Whipple operation, is complex and has significant risks. Oncolytic Virotherapy and can cure cancer even where Chemotherapy is not sufficient and is compatible with synergistic treatment, has broad tropism, efficient replication rate and is long-lasting. With the help of UP_210--the Oncolytic Virus (strain of Adenovirus type5) I plan to modify, the challenges faced by immunotherapies like tumour heterogeneity, effective delivery, pathogenicity, toxicity, to normal tissues, immunosuppressive TME, high cost, chances of cancer returning etc. will be significantly minimised.The UP_210 virus incorporated a strong promoter Survivin which drives selective replication in tumour cells and can survive through the harsh acidic and hypoxic conditions of the TME. The E1 gene has been deleted. By deleting E1, the virus can only replicate in cells that have specific defects in the Rb and p53 tumour suppressor pathways, which are commonly altered in cancer cells. The inserted GM-CSF Factor stimulates the proliferation and activation of immune cells, particularly dendritic cells, which are crucial for initiating immune responses. Incorporating shared introns, allows for alternative splicing of mRNA, enabling the expression of different protein isoforms from a single gene. TRAIL (TNF-Related Apoptosis-Inducing Ligand) induces apoptosis (programmed cell death) in tumour cells by binding to death receptors on their surface. By incorporating 2A Peptides, the gene lengths are shortened further. TNF (Tumor Necrosis Factor) promotes inflammation and can induce apoptosis in certain cancer cells. The shared silencers modulate gene expression by repressing transcription in non-target cells. IFN-α (Interferon Alpha) enhances the immune response and has antiviral properties. CCL2 (C-C Motif Chemokine Ligand 2) recruits immune cells, particularly monocytes, to the tumor site. CCL5 (C-C Motif Chemokine Ligand 5) attracts T cells and other immune cells to the tumor microenvironment. FLT3L (Fms-Like Tyrosine Kinase 3 Ligand) promotes the development and activation of dendritic cells. CXCL11 (C-X-C Motif Chemokine Ligand 11) attracts T cells to the tumor site. Anti-PD-1 (Immune Checkpoint Blockade) blocks PD-1 receptor enhancing T cell responses. The BiTE using MUC1 and CD3 and Monoclonal antibodies (mAbs) receptors bind to EGFR receptors overly expressed in lung and pancreatic cancers. The BiTE attaches one receptor on the tumour and other to a T cell promoting lysis. The 4-1BBL activates T cells and promotes their survival and proliferation while the OX40L produces long-lasting resistance to tumour recurrence. All these genes are expresses once the virus replicates inside the host cell. Upon virus internalization through receptor-mediated endocytosis, the viral particles are disassembled and exposed capsids that enter the cytoplasm by lysis of endosomal membrane and are subsequently transported along microtubules to the nuclear envelope, where viral genomes import into the host nucleus. Adenoviruses are one of the most widely studied viruses because they provide several advantages, such as the feasibility of manufacturing high viral titers, ease of genome manipulation, and inherently potent lytic activity. Like cytokines, BiTE and TriTE molecules have drawbacks such as short biological half-life, rapid excretion, poor residence time in TME. Luckily, the problems could be solved when they become a team with OVs.

**ENTRY FOR STEM PROJECT CONTEST** --->Background: Why I want to win the contest Since childhood I have been involved in fishkeeping (actually when I was 4) which, led me to Biology. I live in Bangladesh, where the average wage of a person is a bit over 200$, which is why I have always known that I am much much privileged than that of many other students like me. But this has also led to the reason I cannot invest much into my STEM projects. One day, while browsing Facebook I saw that tissue culture aquarium plants were being imported from various parts of the world and being sold for a very steep price; something that led me to wonder, why doesn't Bangladesh produce it themselves? I found out that although tissue cultured banana plants were produced by government organizations, no one was able to produce plants commercially due to the steep price of the setup and chemicals required to do it. --->The Project: Finding a BETTER & COST EFFECTIVE SUBSTITUTE!! This led to me to work on minimizing the biggest cost, getting MS media (a.k.a. Murashige & Skooge). Currently I am working on methods and substitutes of the media, which gives the same result if not the same as MS media. I had talked to many of the lab Heads of some of the best agricultural Universities of Bangladesh, many of them have helped me supplying some of the ingredients I need for the research. The PROOF that I am working on this can be seen from the attachments I am sharing (but of course, these are not the current work I am doing but the drafts, of when I was first starting). I believe in the freedom of access to knowledge and resources, especially when that free access can help another person push the frontiers of research and knowledge ultimately. I hope you guys vote, not for me But for each and every single person who is deprived of such facilities. Thank you for reading!

I have this project i worked on with 2 other friends, which we presented at a conference and published a research paper for. I've attached the research paper below, its kind of a non profit thing, so this funding would be of great help! I have the presentation and video explaining the project, for further context. Thank you!

🎯I’m trying to determine if I can predict the winning number in a casino game just by analyzing the ball's movements before it lands 👇CHECK THE VIDEO👇 Using a self-coded algorithm I will extract information from roulette games and divide it into input and output data. Then, I will use this dataset to train a neural net. The final goal is to create a tool that, given a video of a roulette play (without the part where the ball lands), can provide a precise approximation of where it will land. In the scheme you can see the basic structure of the video analyzer, which is already developed and I just need to improve and implement it with lots of roulette plays. Regarding the Neural Network, I have some knowledge about how to implement it, but I have not yet fully developed it due to some issues and time restrictions. If you are interested in knowing more about the project, visit the attached document, where I will be updating the project's development. *If interested in giving ideas or commenting about the project, I will gladly read them in this entry. https://docs.google.com/document/d/1aFx7acvxA1EstakfdOgHR2sErDfUbwVy4HMnn6I4Bfg/edit?usp=sharing

Portable CRISPR Device for Real-Time Microbial Detection in Water Sources Any feedback or comments on my project are greatly appreciated! Microbial contamination of drinking water poses significant risks to public health, particularly in areas with limited access to laboratory-based water testing methods (Ashbolt, 2015). Traditional techniques, such as microbial culturing and polymerase chain reaction (PCR), are effective but impractical for real-time, field-based applications due to their cost, time requirements, and reliance on specialized infrastructure (Yu et al., 2005). This study proposes a portable CRISPR-based device for rapid, real-time detection of microbial pathogens in water. The device integrates modular components for filtration, cell lysis, genetic material extraction, and CRISPR-Cas12/Cas13-based detection, with fluorescence or colorimetric outputs to provide accurate and timely results (Tian et al., 2024). Methodologies for pre-filtration, lysis chamber design, and CRISPR reaction setup are outlined. Future advances include AI-enhanced signal analysis and multiplexed pathogen detection. Why Does This Matter? Current water testing techniques often fail to meet the needs of vulnerable populations due to their complexity, cost, and dependence on laboratory infrastructure. My device bridges this gap, providing a simple and effective solution to detect waterborne pathogens in real time. With potential applications in households, disaster zones, and industrial water monitoring, this device could significantly improve global health outcomes. The funding from this contest would enable the acquisition of necessary materials for further testing and optimization. If you believe in the power of innovation to solve the water crisis and save lives, consider supporting this project! https://docs.google.com/document/d/1mEhQnTgx47RrZWAklg6OH4O4qSzfmooUIxwN3uVEqFA/edit?usp=sharing