Difference between revisions of "Part:BBa K1897007"

Revision as of 20:36, 11 October 2016

Complete Has operon (controlling expression of luxR)

Usage and Biology

The Has operon is originally a heme acquisition system from the Serratia Marcescens. In the original system, HasA, a hemophore, is secreted out of the bacteria to capture extracellular heme. This holo-HasA then binds to the cell surface receptor HasR. This causes a conformational change in HasR and activation of anti-sigma factor HasS. HasS then releases the extra cytoplasmic function sigma factor HasI. HasI then allows the expression of genes controlled by the Has promoter (pHas).

NUS_Singapore utilises this system to create the RIOT Sensor, one of its two spatial sensors in the RIOTSystem. THe RIOTSystem is a spatially specific cancer diagnostic that relies upon spatial markers that are unique to the tumour microenvironment to allow for specific detection of the tumour. One of the two sensors employed detects the presence of CD44v6, a commonly upregulated cell surface marker on a variety of cancers (Todaro et al., 2014). This is done by conjugating HasA with a CD44v6 antibody (RIOT Transponder). Therefore, the the conjugate can attach to the surface of cancer cells and the holo-HasA would be able to bind to HasR expressed on the E. coli containing the RIOT Sensor. This would then trigger the expression of luxR which is under the expression of the pHas (Figure 1)

Todaro, M., Gaggianesi, M., Catalano, V., et al., (2014). CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell stem cell, 14(3), 342-356.

Sequence and Features