What are you working on at the moment?
Mike: We’re developing an alternative testing method to the one being used at the Crick and most testing facilities around the world. To test for the presence of SARS-CoV-2, the virus that causes COVID-19, you need to know how much of the virus’ genetic material is present in the sample that you’ve been given.
A patient’s sample may only contain very small amounts, below what many tests can decipher. The testing techniques used at the moment generally rely on a method called RT-qPCR, a multi-step process that involves multiplying specific sections of the virus’ genetic material until you have millions of copies that can be accurately detected.
It involves cycling many times through several different temperatures in order to amplify the material for detection. This method might not be a sustainable way to meet the demand for widespread regular testing because the materials needed are now in extremely high demand and the technique requires sophisticated and expensive equipment.
Enzo: The alternative method that we’re developing uses RT-LAMP, which delivers results in a third of the time that RT-qPCR takes and is much cheaper. RT-LAMP is a single stage process and doesn't need any specific equipment other than a heater.
The procedure is carried out at one temperature and can be combined with a colour-based indicator that simply changes from pink to yellow when the sample is positive for SARS-CoV-2.
We are also working on removing the need for the first step in the process, which involves purifying RNA from a patient sample. This means our technique could be used directly in hospitals and not just in testing labs. In theory, this could also remove the need for the test to be carried out by an expert.
How far have you got?
Mike: We have validated the method with patient samples, so we have high hopes that it will become available for wider use soon. Just like with the testing pipeline that we already have at the Crick, we’ve been collaborating with other researchers, hospitals, institutes, and companies to move this forward not only in the UK, but perhaps elsewhere.
Enzo: We’ve shown a few key strengths of this alternative testing method. Firstly, it’s sensitive, meaning that we can be confident it will pick up a positive sample. Secondly, it’s highly specific and won’t pick up other respiratory infections or coronaviruses. And lastly, it’s less expensive and reduces turnaround time for results.
We’re really excited that it might soon be used for diagnostic purposes. Once there is a lower prevalence of the virus, there’s also a chance that the technique could be used for mass testing in the general population to track the virus because the method is easily scalable for a high throughput format and requires fewer materials than conventional testing, allowing it to be implemented widely.
What do you usually work on at the Crick?
Mike: We’re both second-year postdocs in Caetano Reis e Sousa’s lab, which studies the immune system. My project focuses on the regulation of the development and function of a group of immune cells called dendritic cells, which are responsible for initiating and coordinating the immune system’s response to invading pathogens and cancer.
The more we understand about the biology of dendritic cells, the greater the opportunity we have to harness them in a targeted way for cancer therapy and the development of new vaccines and immune-based therapies.
Enzo: I’m investigating how stem cells fight viral infections. We know that they don’t respond to type-I interferon, which is a key molecule responsible for setting up early antiviral immunity in mammals. However, they are quite resistant to viral infections, suggesting that they display alternative, unknown mechanisms of protection against viruses. That’s what I’m trying to shed light on.
How did your involvement in the testing project come about?
Mike: Lots of people around the Crick started to discuss this alternative testing method after another organisation published the technique in a preprint. We were excited about the possibility of implementing this at the Crick, so we joined a Slack channel that was started by others in the institute also interested in developing alternative testing strategies.
Our group leader, Caetano, and George Kassiotis, another group leader at the Crick and fellow immunologist, approached us about focusing on this project as we have experience in working with highly pathogenic viruses. After we received grant funding from the Rosetrees Trust and The John Black Charitable Foundation, we became focused on this project full-time.
How has the way you work changed?
Enzo: In order to limit the spread of SARS-CoV-2 within the institute and protect staff at the Crick, until this week the only people that have been allowed into the building were those critical to COVID-19 testing, SARS-CoV-2/COVID-19 research and the maintenance of the Crick’s research infrastructure.
It wasn’t possible for us to continue our postdoc projects so we initially volunteered to help with the Crick’s testing efforts. We were able to use our previous experience working in the containment facility to inactivate the virus in patient samples. When a sample arrives for testing, it is still potentially contagious. This step effectively removes the chance that the sample will be able to pass the virus onto anyone that it comes into contact with as it goes through the testing pipeline. Now we’ve fully transitioned to our work on investigating alternative testing methods for SARS-CoV-2.
We’ve reconfigured our lab space and cordoned off an area for us to work in. Bruno, Ana and Johnathan from our lab are also helping with this project and there’s a real push to get this going. We’re both really motivated to see it in action as soon as possible.
How have you found working on the project?
Mike: I feel a sense of purpose, especially because we’re able to use our previous experience and training with viruses and molecular biology for this work. The goal is to make this technique freely available so that other institutes and countries can implement similar strategies.
I’m thankful we have the opportunity to do this at the Crick, despite everything else being essentially shutdown. During a crisis, it’s great to know that the institute is being used for a good purpose.
Enzo: In basic science, we rarely see the applications of our work as progress is so incremental and clinical impact can take several years, if not decades, but now things are moving much faster. It’s a real novelty that we’re seeing the positive impact of our work almost immediately.
As the project moves along, we’re seeing more and more avenues for application, and the immediate reward is very satisfying. We’re proud to be a part of the volunteer efforts here at the Crick and use our resources to serve the public during this pandemic, and we’re very grateful to have the support of The Rosetrees Trust and The John Black Charitable Foundation who have, until now, enabled us to focus on this work full-time.