California biologists have developed a way to give engineered bacteria ‘thermostat controls’ in a new development aimed at fighting cancer and diseases of the gut.
A new study out of the ShapiroLab at California Institute of Technology in Pasadena (Caltech) shows genetically-altered bacteria engineered to respond to temperature could be sent into the body to fight disease. By manipulating the temperature around them, such as heating the tissue by ultrasound, it is possible to trigger when and where they release medicine, and when they might need to self-destruct.
Caltech, and the wider California life sciences community in general, is making strides in the growing field of microbial therapeutics, the strategy of using engineered bacteria to fight disease. Mikhail Shapiro is Caltech’s assistant professor of chemical engineering and Heritage Principal Investigator, whose overall research goal is to create new ways to both visualise and control cells — bacterial cells and human cells — for medicinal purposes. The ShapiroLab engineers biomolecules with unusual physical properties and uses them to image and control biological function non-invasively, for example using magnetic fields and sound waves.
Shapiro says: “Bacteria can be designed to act like special agents fighting disease in our bodies. We’re building walkie-talkies for the cells so we can both listen and talk to them. We can use these thermal switches in bacteria to control a variety of behaviours.”
Microbes are already being tested for their ability to fight disease, but currently they can travel to other organs, releasing medicine in the wrong part of the body and lessening the effect of the treatment or causing side effects. To combat this, the Caltech researchers developed a technique to control where the bacteria travel, and make sure they only target the desired areas using thermal cues.
The researchers sought out genetic switches that already depend on temperature, and settled on two candidate proteins: one from Salmonella, and another from a bacteriophage. Next, they used a protein engineering technique — ‘directed evolution’ pioneered by Caltech’s Frances Arnold, Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry — to generate versions of the proteins that activated at temperatures between 36 and 39 degrees Celsius. These genetic switches can act like thermal controls, turning the therapy on or off at a given temperature.
In theory, a doctor could administer genetically-altered bacteria to a cancer patient and then, by focusing ultrasound at the tumour site, trigger the bacteria to fight the tumour. These thermal cues could also terminate the engineered bacteria if the temperature gets too hot, in the case of a fever which might indicate that a patient isn’t responding well to the treatment; or too cold, if they were passed out of the body through defecation, alleviating concerns about genetically modified microbes spreading into the environment.
“When we were thinking about how to get bacteria to sense temperature, we looked at nature and found a few systems where bacteria can do this,” says Dan Piraner, co-lead author of the study. “We tested the performance, found the ones that had the best switching performance. From there, we went on to find that they could be tuned and amplified. It all started with what nature gave us, and engineering took us the rest of the way.”
(via Caltech and New Atlas)
Featured image: Caltech research may allow doctors to instruct engineered bacteria in a patient’s body when and where to administer drugs using thermal cues (Credit: Barth van Rossum for Caltech)