A collaborative study by the Crick, UCL and UCLH NHS Foundation Trust, LEGACY was established in February this year to better understand how and why people are vulnerable to infection with SARS-CoV-2.
The study originally built on the unique bank of more than 400,000 COVID-19 test samples held at the Crick, and continues to gather samples from healthcare workers and Crick employees in collaboration with UCLH.
The team has already published data on the ability of antibodies in the blood of vaccinated and previously infected people to neutralise SARS-CoV-2, and has now turned to look at the Omicron variant.
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In early March, a team of researchers from the Crick and King’s College London released results from the SOAP study, the world’s first reported trial examining the level of immune protection after the Pfizer-BioNTech vaccine in cancer patients.
The team found that cancer patients showed very low levels of immune protection after one vaccine compared to healthy control participants.
Although a second dose after three weeks improved the immune response significantly for solid cancer patients, the team found in this and a later study, also completed in 2021, that most blood cancer patients still displayed poor antibody responses to two doses of the vaccine, and that delaying the second dose did not represent a substantial advantage to the original recommended vaccination schedule. The work remains relevant as blood cancer patients are understandably anxious over their levels of protection against current and future variants.
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At the start of the pandemic, teams across the Crick were busy developing viral antigens that could be used in SARS-CoV-2 serological testing and repeatedly came across an unexpected green colouration in some samples.
They discovered that the green colour was caused by the virus’s spike protein binding with biliverdin – the molecule responsible for the green colour in bruises. The researchers found that biliverdin and another molecule called bilirubin suppressed the binding of some human antibodies. In some cases, biliverdin reduced the ability of the spike protein to recognise patient antibodies by as much as 50%. This could help to explain why some people can become severely ill with COVID-19, despite having antibodies against the virus.
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Tube containing the green coloured COVID-19 protein, with the colour the result of the spike binding with biliverdin.
In April, researchers revealed that CRISPR-Cas9 genome editing can lead to unintended mutations at the targeted section of DNA in early human embryos.
The study went back and looked a data from previous research studying the role of a specific protein in the early stages of human development. The team found that while the majority of CRISPR-Cas9-induced mutations were small insertions or deletions, in some of the samples, there were large unintended mutations that would have been missed by conventional methods to assess DNA changes.
The work highlighted the need for greater awareness of and further research into the effects of CRISPR-Cas9 genome editing, especially when used to edit human DNA in laboratory research.
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In August, scientists from the Crick and UCL published two papers on the potential mechanisms of motor neurone disease or amyotrophic lateral sclerosis (ALS).
In ALS, proteins build up in the wrong parts of brain cells. The first paper focused on aberrantly retained sections within RNA called introns, and found that in cells with ALS, there was a much higher number of intron-retaining transcripts in the cells’ cytoplasm than previously expected. Noting that these aberrantly retained introns bind avidly to specific proteins, this may underlie their mislocalisation to the cytoplasm. The second paper demonstrated how it might be possible to reverse this protein mislocalisation in some cases of ALS.
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