Tackling COVID-19 at the Sanger Institute
By Alison Cranage, Science Writer. Illustration by Alex Cagan, Postdoctoral Researcher at the Sanger Institute.
Staff at the Sanger Institute have joined the fight against the global COVID-19 pandemic. Projects and collaborations have been initiated, from investigating the cellular receptors the virus uses to invade our bodies, to understanding how the immune system may play a role in disease severity. We also are working with public health laboratories, Institutes and Universities across the UK to sequence SARS-CoV-2 virus genomes to trace its spread.
Some laboratory staff are joining national testing centres and others are volunteering in their local communities.
Below is a summary of our current efforts. We will update this article over the coming months as our work continues.
SARS-CoV-2 Genome Sequencing
Researchers in the Sanger Institute Cellular Genetics programme, led by Dr Sarah Teichmann, have analysed multiple Human Cell Atlas (HCA) datasets to investigate where COVID-19 may enter the body. These vast datasets are cellular maps of the body, built using single cell RNA sequencing to show which of our cells are using which of our 20,000 genes. The data can reveal which proteins are active in any given cell, and are available online at www.covid19cellatlas.org
The researchers looked for individual cells that had both of two key virus entry proteins present; ACE2 and TMPRSS2. Two specific cell types have been identified as likely initial infection points for COVID-19 coronavirus – goblet and ciliated cells in the nose. This makes these cells the most likely initial infection route for the virus. Some cells in the eye and intestines also contain the viral-entry proteins. The findings are helping researchers understand exactly how the virus is transmitted between people and spreads.
While there are many factors that contribute to virus transmissibility, the findings are consistent with the rapid infection rates of the virus seen so far. The location of these cells on the surface of the inside of the nose make them highly accessible to the virus, and also may assist with transmission to other people.
A consortium of researchers from the Cellular Genetics Programme are using cell atlas technologies to analyse COVID-19 patient samples, including paediatric and adult patients, young and old adults, mild and severely affected patients. This coherent effort to analyse the blood and tissue response to infection in depth includes analysis of the placentas of infected mothers by Dr Roser Vento-Tormo, to gain insight into possible pathways of transmission from mothers to babies.
A further initiative led by Dr Roser Vento-Tormo and Dr Esteban Ballestar from the Josep Carreras Research Institute, which has received funding from the Chan Zuckerberg Initiative, is looking at nasal and blood samples in up to 50 COVID-19 patients with pre-existing immune disorders, including rheumatoid arthritis and multiple sclerosis. By creating a cell atlas of the immune cells involved in tackling SARS-CoV-2, the research will provide insights into human susceptibility to SARS-CoV-2 infection and how the immune system reacts to the virus.
Update: Data on these immune cells from the COVID19 Cell Atlas have been shared before analysis and publication of the results, to maximise the benefit to coronavirus research worldwide. The data are now available at https://covid19cellatlas.org, hosted in collaboration with the Chan Zuckerberg Initiative.
Dr Kerstin Meyer, a Principal Staff Scientist at the Sanger Institute, is working with Dr Marko Nikolic at University College London (UCL) to investigate why children are relatively unaffected by the SARS-CoV-2 virus. They are looking at the presence of the viral entry genes ACE2 and TMPRSS2 in cells from the nose. They are also studying the immune response to the virus – they will identify and characterise the cell types that are responding to infection, and follow these over time.
The team will use single cell transcriptomics, combined with protein profiling (CITE-seq), as well as serum analysis and genotyping, to study children infected with SARS-CoV-2 with both mild and severe symptoms. Their study design is aligned with a similar study in adults, led by Professor Menna Clatworthy and Professor Muzlifah Haniffa, allowing them to study and contrast samples from patients of different ages. Understanding the molecular changes that drive disease severity could help understand how best to treat patients, as well as assist in the development and evaluation of safe vaccines.
There are other research projects underway, or starting up, across the Institute. We’ll update this post with more details over the next few weeks.
PPE, reagents and mice
We have shared available personal protective equipment (PPE) with local NHS services, and are exploring more ways that we can help. Viral extraction reagents that we had ordered have been diverted to national testing centres.
Over the last couple of weeks, Infrafrontier, a European organisation that runs a mouse distribution and repository service for scientists, has asked if we house mice with the key genes for COVID-19 research.
We have supplied four different mouse strains and have offered to provide support by distributing our in-house stocks should this need arise. The staff who run our animal facility have been looking at new ways of working to further increase overall resilience. Whatever research happens, their top priority remains the care and welfare of the animals.
In response to the Government call for experienced laboratory staff to support national testing centres, we are supporting any staff who wish to do this on secondment. Staff will continue to be paid by the Institute rather than the testing centres.
For those wishing to help in other ways volunteering leave has been extended for 2020 for COVID-19 related activity.
Keeping staff safe
The majority of staff are working from home and Campus access is being closely managed to keep numbers on site to an absolute minimum. But for our key workers on site – those working on COVID-19 research projects, looking after our animals and staff from our catering, security, cleaning and facilities teams – we have introduced additional measures to keep them safe.
As well as following government guidelines on hand washing and staying two metres apart, we’re spreading out across Campus to make use of the space we have available. Our cafe, for example, has been reconfigured to allow social distancing. We’re allocating larger rooms for working areas and making use of remote-working technology even within rooms and buildings.
💜Love that tables in DiNA @sangerinstitute are helping our critical staff practice physical distancing on their well-earned breaks
<—-2m—-> 📐🧮📏 Brilliant teams supporting each other! 🙏🏼😊 pic.twitter.com/fLvHnGMxqk
— Dr Cordelia Langford (@CLongstaff) March 25, 2020
We’ve increased our cleaning regime and have placed hand sanitiser stations in communal areas.
We’re regularly reviewing the situation to make sure we’re doing all we can, with regular communications going out to those working on Campus to make sure everyone is informed about how to stay safe.
Staff have been keeping in touch, whether they are working on Campus, or from home where they are joined by family members and pets.
We want to take a moment to celebrate all of our staff who are working so hard from home. They’re supporting our critical research on @wellcomegenome and keeping the institute going! 🎉#SangerAtHome #WorkingFromHome pic.twitter.com/hhnI6ZDrkv
— Sanger Institute (@sangerinstitute) April 17, 2020
“We believe it’s important for us to contribute to the national effort, utilising our technology platforms, to join the fight against this virus. Staff from so many different teams are bringing their skills and experience to the fore to combat this pandemic, and we are incredibly proud of them.”
Dr Cordelia Langford, Director of Scientific Operations