Publication highlights

COVID-19 restrictions including social distancing were lifted in the UK in 2021 after the majority of the population had two doses of vaccine. Researchers at the Crick analysed data from the Legacy study to find out if either infection or vaccine as a third exposure generated different immunity. We found overall that both antibody-mediated and cellular immunity was similar, but when T cells were exposed to spike protein challenge in vitro, infection exposure drove production of more innate immune cytokines from T cells and expansion of mucosal-homing T cells, whereas vaccine-only exposed cells led to expansion of the T cell memory population that produced more inflammatory cytokines.

Researchers at the Crick looked at genes in single cells in opossums during early development of organs to characterise temporal shifts in development, known as heterochrony. Although development in marsupials is relatively slow until gastrulation, they then accelerate development of tissues, particularly features required for locomotion and feeding, e.g., craniofacial structures and forelimbs. The team found that, during development, genes are read earlier and more quickly than in placental mammals. This led to neural crest cells migrating before the neural tube closes, motor neurons forming before the spinal cord closes, and patterning of future limbs coming before limb bud outgrowth - all these features are different from placental mammals. Their findings suggest that differences in protein production rates could regulate this phenomenon of heterochrony.

Type 2 immunity is central to parasite protection but when dysregulated causes allergy and atopy (tendency to produce an immune response to allergens), and influences neuroprotection, ageing and cancer. Researchers at the Crick have discovered two new ways the receptor for the type 2 cytokines IL-4 and IL-13 (called IL-13Ra1) is modulated. One is sex-specific – female hormones repress expression of this common receptor so that female cells are less responsive. The other is through an ancient retrovirus that integrated near the IL-13Ra1 gene of our primate ancestors, which produces a partially defective IL-13Ra1 that can block the traditional version from signalling. This is a fascinating example where an ancient retroviral infection has affected modern human immunity.

Researchers at the Crick, the UCL Cancer Institute and UCLH have shown that a test called ORACLE can predict lung cancer survival at the point of diagnosis better than currently used clinical risk factors. This could help doctors make more informed treatment decisions for people with stage 1 lung cancer, potentially reducing the risk of the cancer returning or spreading. ORACLE was developed in 2019 to overcome the lack of biological markers in lung cancer, which is important for people with stage 1 lung cancer, who are normally given surgery without chemotherapy. In this study ORACLE was validated in 158 people with lung cancer in the Cancer Research UK-funded TRACERx study. The team found that ORACLE could predict which patients with stage 1 lung cancer had a lower chance of survival, and might benefit from chemotherapy as well as surgery. The researchers also found that high ORACLE risk scores were linked to regions of the tumour that were more likely to spread to another part of the body.

Small molecule probes offer powerful tools for the study of biological systems and can serve as starting points for the development of therapeutics. The vast majority of human proteins lack such chemical tools, which hinders our ability to explore their function in the context of health and disease. Screening libraries of “reactive fragments”, small molecules that form covalent bonds with their protein targets, by mass spectrometry enables the discovery of new ligands in the native cellular environment. Together with GSK as part of the Crick-GSK Biomedical LinkLabs Prosperity Partnership, researchers at the Crick have developed a robust and versatile proteomics platform for profiling of cysteine-reactive fragments against the native proteome and have identified hundreds of new protein-ligand interactions for probe development.

Researchers at the Francis Crick Institute and UCL, funded by Cancer Research UK, have unveiled the first computer algorithm capable of identifying which cell populations within a tumour drive aggressive growth. The innovative algorithm, called SPRINTER, analyses individual cells within a tumour to identify those that are growing the most rapidly. The algorithm was used to analyse nearly 15,000 cancer cells from a patient with non-small cell lung cancer (in TRACERx and PEACE studies). SPRINTER revealed that the cells that were growing the fastest were responsible for spreading the cancer to other parts of the body, even from other metasasised tumours. It also showed that these cells shed more of their DNA into the bloodstream. The possibility of detecting aggressive cancer cell populations early and monitoring them over time offers a new avenue for more proactive and personalised cancer care.