Support Undergraduate Research in Synthetic Biology!

Help send the UO iGEM team to Paris to share their project on the world stage and support research that has potential life-saving impact!

The UO iGEM (International Genetically Engineered Machine) team is a research group of undergraduate students working in the Knight Campus for Accelerating Scientific Impact. We are a diverse, motivated team focused on solving real-world problems using synthetic biology. Our members come from a variety of scientific backgrounds, including Biology, Chemistry, Biochemistry, Human Physiology, and even Business! In 2022 we designed a rapid, low-cost biosensor for detecting concussions. In 2023 we set our sights on engineering a probiotic to fight gut infections, and we’ve since adapted our idea to be modular. 

The Paris Jamboree is a scientific conference where iGEM teams from around the world collaborate with each other to advance the field of synthetic biology and network with big industry players. This year there will be more than 5000 attendees, representing 400+ teams from 66 countries. Attending the conference will allow us to present our work on the world stage, putting the University of Oregon on the map. We will present our research to students from the top universities in the world, as well as leading companies in the synthetic biology industry. We can join startup incubator programs to turn our proof of concept prototype into a fully fledged therapeutic, and participate in the scientific process with other iGEM teams from the rest of the world.

Attending this conference will greatly benefit our students' professional development. This Jamboree will expose our members to industry and technology that is only accessible to them during this conference. Our students are ambassadors of the University of Oregon and this opportunity allows us to share our journeys and learn from professional feedback. The Jamboree in Paris gives undergraduate students a chance to see high level synthetic biology that would otherwise have a barrier to entry.

Our research has profound potential benefits in medicine. Enterohemorrhagic Escherichia coli (EHEC) is a food and waterborne pathogen that causes diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS) in humans. In the U.S., EHEC causes an estimated 63,000 hemorrhagic colitis cases annually in the United States; and 2.8 million globally. 10% of EHEC infections progress to HUS, which can then accelerate to additional life-threatening complications such as kidney failure. A probiotic strain effective against EHEC can also be easily re-engineered to target any pathogen in the GI tract, making our treatment adaptable to many potential uses.

Research is expensive! Our experimentation will likely cost around $10,000. This includes the purchase of DNA, bacteria, reagents, single-use lab supplies, and more. Our work does not proceed without these things, so your contribution allows us the freedom to develop our work from ideas and plans to tangible results. 

Travel costs for one student is  $3,400, and we can only afford to send three of our twelve team members with our current funds. Sending more students means that those who worked on specific aspects of the project can explain their own work. We will be able to answer more nuanced questions at the conference, pertaining to the work of specific team members and helping us put our best foot forward. A convincing presentation could open our project to support from startup incubators and  launch our research into the commercialization and mass production stage.

See below for detailed information about the project.

HGT: Hostile Gene Transfer

An engineered probiotic bacterium that eradicates EHEC

Our Motivation

Escherichia coli (E. coli) is a genetically diverse group of bacteria. Although many E. coli strains are nonpathogens and commensal gut microbes, various strains have acquired genes that increase their virulence. Enterohemorrhagic E. coli (EHEC) is a gram negative bacterial pathogen that causes severe gastroenteritis, including stomach cramps and bloody diarrhea, and in severe cases, hemolytic uremic syndrome (HUS) and neurological disorders [2]. It’s estimated that EHEC causes 63,000 hemorrhagic colitis cases annually in the United States, and 2.8 million worldwide [1]. EHEC infections are largely attributed to consuming contaminated food or water. 

EHEC colonizes the small intestine by a distinctive attaching and effacing lesion (AEL), in which it delivers toxins to kill intestinal epithelial cells and utilize their nutrients [3]. EHEC produces a cytotoxic protein called Shiga toxin [4]. Shiga toxin dismantles a cell’s ability to carry out protein synthesis, a key cellular process all cells need for survival. Just one molecule of Shiga toxin is enough to kill a eukaryotic cell. This potent protein toxin is just one of EHEC’s tools in causing disease. EHEC carries the genes for a conjugative secretion system, which it uses to directly inject Shiga toxin into intestinal epithelial cells [5]. It also secretes a hemolysin, serine protease, a catalase, a zinc metalloprotease, and other protein toxins. The activities of these secreted proteins all coordinate to damage intestinal epithelial cells and circumvent their vital nutrients to fuel the growing EHEC AEL. This all results in severe damage to the intestinal lining, inflammation, abdominal pain, and life-threatening HUS and kidney failure. The best tools we have today to fight bacterial infections are broad spectrum antibiotics, which have become significantly less effective in recent years [9]. 

EHEC has developed unique and deadly responses to antibiotics. Studies show that exposure to commonly prescribed antibiotics, including ciprofloxacin [6] and norfloxacin [7], increases EHEC secretion of Shiga toxin, thus significantly worsening symptoms and accelerating the onset of HUS. The only treatments available are hydration and fluid replacement in mild cases, and hemodialysis in cases with HUS complications [1]. We are running out of options that work as EHEC and other bacterial infections are beginning to become resistant to even “last resort” antibiotics  [10]. 

Our Project

Using our team’s expertise in genetic engineering and the support of the global iGEM network, we will develop a genetically modified bacterium that seeks and destroys EHEC in the gut. We’ll be working with “Nissle 1917” a probiotic strain of E. coli that’s already in use in the US for treating certain GI conditions and is sold under the brand name Mutaflor®. Since this bacterium has already been granted Generally Recognized as Safe (GRAS) status by the FDA, our path to deployment is significantly easier than other groups which start from scratch and need to secure their own FDA approvals. 

Our engineered strain will specifically recognize EHEC cells using engineered protein binders, and deliver a malicious DNA payload through a process known as “horizontal gene transfer”. Once injected, this DNA will disrupt the biofilm-forming colonies and trigger the injected cell to kill itself. This is the same principle as cutting edge “phage therapies”, but using bacteria allows us to deploy our treatment at a significantly lower cost while having a greater control over the specificity of our attacks.

We are taking a uniquely modular approach that will allow future work to modify our platform to be targeted towards nearly any pathogenic GI tract bacteria, and allows us to develop these parts in parallel. Other common pathogen examples, such as Salmonella typhi (responsible for typhoid fever), Helicobacter pylori, Salmonella enterica, Clostridioides difficile could also be targeted using our system.

Bacteria in our gut outnumber our cells 10 to 1, and every person’s gut microbiome is slightly different. It’s impossible to say how many of these bacteria could turn into a bacterial infection, but we could build and deploy a new version of our strain in months to target that species directly.

By engineering a novel conjugation mechanism to deliver a fatal DNA payload, we are able to create an E. coli-based therapeutic that is specific, modular, and safe. Our E. coli-based solution does not rely on the use of antibiotics, which can be harmful when used repeatedly in high doses, and are becoming increasingly ineffective against bacterial infections.

We believe that every little step we take today can make a difference in the lives of countless individuals in the future. It is with utmost sincerity and gratitude that we seek your benevolent support to make our participation in this convention a reality. Our vision for an antibiotic-free future in bacterial infection treatments can become reality with your support. Additionally, your support could send a student to the Paris Jamboree and give them an incredible networking opportunity they’ve worked to earn. Your commitment to empowering the next generation of researchers and change-makers will undoubtedly leave an indelible mark on our team, university, and the world at large.