Team:Alabama/Description

Problem Statement:

Pancreatic ductal adenocarcinoma (PDAC) is a prevalent cancer up 3.2% of all new cancer cases and an estimated 56,770 new cases have popped up in 2019 alone. Despite the small percentage of cases it makes up, it is the cause of 7.5% of all cancer deaths and an estimated 45,750 people have died from it in 2019. Previous reports have shown that intratumor bacteria causes a large role in the tumor’s ability to become resistant to one of the main drugs used to fight this cancer, gemcitabine. Gemcitabine is a chemotherapy drug that in addition to pancreatic cancer, is used to treat breast, bladder, ovarian, and non-small cell lung cancer. Studies show that 1.6% of men and women will experience PDAC. Only 9.3% of people with PDAC survive for 5 years. It is the 11th most common form of cancer.

Project Summary:

This summer we further explored the previously reported link between the intratumoral bacterial environment of pancreatic adenocarcinoma to confirm and characterize the direct consumption of gemcitabine by comparable bacteria such as some strains of E. coli. It has been shown that the production of a specific type of the cytidine deaminase (CDD) protein by these bacteria render the gemcitabine unusable to treat the target cancer. We constructed a plasmid and used it to knock out the cdd gene from E. coli BL21(DE3), and compared growth of knockout and wild-type strains. Degradation of gemcitabine by the wild-type strain was determined by HPLC. We further developed a suite of modular E. coli expression plasmids, with each plasmid component flanked by a unique restriction site, that will facilitate cloning in the future.

Project Inspiration:

As a first year team, we have been trying to find a sponsor inside or outside of the university for the last 3 years. In 2018, Boston Scientific’s internal cancer solutions group agreed to sponsor the iGEM team to work on a project relating to relevant research with a few different chemotherapeutic drugs the company works with to expand their knowledge base on general cancers with a focus on PDAC. We agreed to this as it would not only provide us funding but laid out a clear path ahead of us.

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