Spotlight on Maria Greco

Back in March, a team at the Crick were working to set up an urgently-needed coronavirus testing facility, but supply chain issues threatened to slow it down. Principal laboratory research scientist Maria stepped in. She adapted a method that she uses to extract DNA from ancient samples to extract the genetic material from the virus ready for testing. Here, she tells us what it was like to be involved in the early days of the testing service, and how she developed the RNA extraction method that doesn’t rely on pre-made kits.

What are you usually focused on at the Crick?

Maria Greco.

I’m part of Pontus Skoglund’s Ancient Genomics lab. My work before the pandemic focused on using the Bravo robot to extract DNA from ancient samples and generate libraries of genetic information for NGS (next-generation sequencing) in our dedicated clean room.

Just like my work with Covid-19, it’s a demanding task that requires a delicate workflow, and we need to use special PPE. Although this is to avoid introducing modern DNA into the room, rather than to prevent becoming infected!

Before I joined the Crick, I graduated as a molecular biologist and worked on epigenetics and gene regulation for my PhD and postdocs. Then five years ago, I changed fields and moved to developmental biology, studying how certain regions of DNA (called CNEs) lead to abnormalities and disease in human embryos as part of the Deciphering Developmental Disorders (DDD) study.

I developed a kit-free RNA extraction method. I had just 3 or 4 days to adapt the method before we launched.

Before joining the Skoglund lab, I worked in the Crick’s Genomics Facility where I learnt all I know about automation, like how to work with robots and liquid handling machines. I collaborated with labs interested in introducing cost-effective and scalable ways of running their assays using our equipment, such as James Turner and Kathy Niakan’s labs. I’m also involved in translational research and clinical trials, mainly with Julian Downward, Charles Swanton and Samra Turajlic’s labs.

How did you first get involved in the Crick’s testing programme?

I’ve been involved in the testing pipeline since the initial set-up stage. I came up with a contingency plan in case we were not able to acquire some of the kit. I suggested testing and adapting the Bravo robot method I work with in the lab as an alternative to the traditional RNA extraction method. The traditional method requires specialised kits,  and since the world was in lockdown, we knew that getting orders on time would be unlikely.

So, I developed a kit-free RNA extraction method. I had just three or four days to adapt the method before we launched on Monday 30 March and I needed to make sure everything was working to perfection. I tested four protocols, made minor modifications to the original method, automated it and then validated it by running real patient samples. The method turned out to be vital as sure enough, a few days before we planned to start the pipeline, we discovered that the kits were stuck and would take much longer to be delivered than we expected. The kit-free RNA extraction method is now the principal method in our Covid-19 testing pipeline. 

The method turned out to be vital as sure enough, a few days before we planned to start the pipeline, we discovered that the kits were stuck.

Are you involved with any other Covid projects?

At the beginning of April, I received an email from Miguel Munoz-Ruiz, a postdoc in Adrian Hayday’s lab. He asked if I was available to help with the Covid–ImmunoPhenotype (Covid-IP) project. It’s a collaboration with Guy’s and St Thomas’ Hospital, King’s College London and  EMBL, which aims to understand the state of the immune system in people who have been infected with SARS-CoV-2. I helped to set up the methods and workflow and ran assays examining the immune response in Covid-19 patients. 

We wanted to identify an immune ‘signature’ for Covid-19 that could be used to predict how different patients will respond to the disease, and how severe each case will be. By studying the role of 770 different 'responders' (using a CAR-T panel, Nanostring nCounter technology) involved in modulating the immune response, we’re trying to identify what’s going on in the immune systems of patients and how this relates to their symptoms.

What has the project found so far?

More than anything else, I’m so glad that the Crick has an array of talented, inspiring and professional volunteers.

Our results from the project are very insightful and they have highlighted the huge amount of information that we can get by measuring the status of very specific types of immune cells involved in fighting the virus. 

The study has already identified a Covid-19 immune signature - key immune cells and molecules that correlate with the patient’s health and how the disease manifests. This might eventually become a routine clinical test to identify early on which patients are at the highest risk. The project has not only improved our understanding of Covid-19, but will help us be better prepared for future infectious pathogens.

In the meantime, other groups working on Covid-19 projects have expressed their interest of applying the technology that I’m using to study the immune response. For example, by studying other groups of patients or using it for diagnostics and clinical trials.

How has it felt to be involved?

I have learnt that the key to success is pulling together, working hard as a group, listening to each other with a humble attitude and putting forward our skills to get the answer as quickly as possible to tackle this global pandemic. I will never forget the support I have received from Rupert Beale and Peter Cherepanov during that hectic but amazing week, as well as the words of appreciation from Charles Swanton and Steve Gamblin.

Although it was an enormous responsibility, it has been more than compensated by the outcome. More than anything else, I’m so glad that the Crick has an array of talented, inspiring and professional volunteers who have made enormous efforts to be at the Crick running the pipeline throughout the last four months. 

At the moment, I’m juggling several different projects, with both Covid-19 screening (in particular streamlining the RT-LAMP pipeline) and diagnostics and my usual work in the Ancient Genomics lab, but it’s a privilege to be involved.

It’s rewarding that after 15 years of working with and developing RNA extraction methods, a method I developed has become a key part of the Crick’s testing pipeline. Though more importantly, it’s great to see the Crick having a major impact by screening frontline health-care workers and giving them the assurance they need to return to work, or quarantine at home.

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