The Idea

Our goal is to develop a cheap, practical, and effective diagnostic test for the parasite T. solium in humans. By reliably identifying carriers of T. solium, treatment can be directed to those who need it, saving resources and avoiding unnecessary side effects. In this way the most dangerous health effects can be averted.

The test will respond to RNA molecules from T. solium in order to detect a tapeworm infestation. RNA (Ribonucleic acid) is the basis of protein production, and every species, including T. solium, has specific RNA molecules which can be used to unambiguously identify it. We plan to take advantage of this in our diagnostic method.

The test will be based on a newly developed method called toehold switch sensors. This method has already been successfully applied to the diagnosis of the Zika virus [3]. We are therefore convinced that toehold switch sensors will also be useful in detecting T. solium.

In order to develop our test, we first need to achieve two things:

1. Production of toehold switch sensors to detect RNA specific to T. solium
2. Creation of model RNA molecules to test Wormspotter

Once these stages are complete, they will need to be brought together so that we can test whether Wormspotter can recognise and react to RNA from T. solium. We aim to achieve this in a cell-free system

The Experiments – Production of Toehold Switch Sensors

Toehold switch sensors are based on synthetic biology. Essentially, they are RNA molecules which code for a reporter protein. They consist of a specific toehold sequence, a ribosome-binding site (which is important for the production of proteins) and a sequence for the reporter protein. The reporter protein can only be produced if the sensor has bonded with its specific target RNA sequence [4]

When producing the sensors, we can select both the toehold sequence and the reporter protein with complete flexibility to match our needs. In this way we can fashion our Wormspotter so that it only sends a desired signal when it binds to RNA molecules specific to T. solium.

We are planning to use T. solium-specific RNA sequences for the toehold sequence and beta-Galactosidase as a reporter protein.

The Experiments – Toehold Switch Sensor Test

We will then combine the toehold switch sensors and model RNA molecules in a cell-free expression system. These systems can produce proteins, just like in a normal cell. However, they are completely synthetically produced, and therefore provide extremely controlled reaction conditions

We will subsequently be able to verify whether the reporter protein beta-Galactosidase was produced in the cell-free system. If it is present after adding our model RNA molecules, this will serve as proof that the toehold switch sensor reacts specifically to T. solium RNA.