Site under construction…
Bacterial Oscillatory Therapy (B.O.T.) aims to fight colorectal cancer,
whose incidence and mortality has increased over past decades. Treatments such as 5-FU chemotherapy
have been shown to be more efficient or have less adverse effects when administered at a certain point of the
circadian cycle (which is known as chromotherapy). We will use E.coli Nissle 1917, a naturally probiotic bacterial strain, that has been reported to target the hypoxic environment of tumours.
The repressilator (a molecular oscillator composed of three transcriptional repressors) will serve to express the anticancer protein called “azurin” in a cyclic time-dependent manner. This drug can bind tumour-specific receptors, adding an extra layer of specificity, and will act by stabilizing p53 tumour supressing gene, which has been reported to have variation on its cellular accumulation during the circadian cycle. Our aim is to achieve the oscillatory release of azurin by E.coli and explore how to achieve stable oscillations with a 24h period within the human gut environment, gaining insights both from wet and dry lab.