Project Description
Here is the map of our project. You can go to the corresponding page by clicking on the picture.
CRC
Colorectal cancer (CRC) is a very common disease resulting from abnormal multiplication of intestinal cells. Causing 1.8 million cases and 862'000 deaths worldwide in 2018 [1], its incidence is on the rise. Traditional methods of treating CRC, notably surgery, chemotherapy and radiotherapy are invasive or have important side effects. They are often used in combinations, but even then their efficiency is not certain, especially in later stages of cancer. This shows a need for new approaches to treat cancer, one of which is chronotherapy.
Chronotherapy
Evidence [2] shows that administration of anticancer drugs at a certain point of the circadian rhythm (day-night cycle) has a positive impact on the treatment efficiency and can lower side effects, which are basic principles of chronotherapy [3]. Our project explores the possibility of combining chronotherapy and bacteriotherapy to explore a new method of fighting cancer.
Our project
We have implemented a two-plasmid system into a probiotic strain of E.coli Nissle 1917.
One plasmid containing a repressilator system assures the periodic regulation of azurin, an anticancer peptide,
which is expressed by the other plasmid. As our bacteria naturally targets tumor environments and azurin has
shown high specificity to cancer cells [4]
we hope to have created an autonomous system, which could be simply ingested by the patient.
Using mathematical models, we have made predictions about our systems characteristics, notably an Individual Based Model and
ODE model of the repressilator, which helped us develop B.O.T even further. It was crucial to assure the safety of our system,
so we have implemented a kill-switch, which will eliminate any bacteria that escape the conditions present in the colon.
Motivation: See what inspired us to do this project!
Learn more about our project:
- Design: dive into the details of our system!
- Human Practices: discover our beyond-the-bench activities!
- Proposed Implementation: a peek into the future!
- Safety: learn how we have tamed our bacteria!