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Explore a selection of research case studies from the past five years.

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Researchers at the Crick are tackling the big questions about human health and disease, and new findings are published every week.

Our faculty have picked some of the most significant papers published by Crick scientists, all of which are freely available thanks to our open science policy.

T Cell in pink

Water influx kicks immune cells into action

T cells are white blood cells that play a critical role in the immune response to pathogens and vaccines. To be recruited into an immune response, T cells must be stimulated through the T cell antigen receptor, which leads to their activation and to cell division. In this study researchers at the Crick show that a protein called WNK1 is essential for this activation process and for cell division. Surprisingly, they were able to show that the reason WNK1 is required is because it leads to an influx of ions (sodium , potassium and chloride), which in turn causes water to to enter the cell by osmosis. Importantly, they show that this water entry is essential for the cells to divide normally. More broadly, they speculate that water entry may be required for cell division by many other cell types, both within the immune system and outside it.

WNK1-dependent water influx is required for CD4+ T cell activation and T cell-dependent antibody responses

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Published in Nature Communications

Published

3D reconstructions of embryonic mouse hearts with Down syndrome

Gene behind heart defects in Down syndrome identified

Researchers at the Francis Crick Institute and UCL have identified a gene that causes heart defects in Down syndrome, by studying human Down Syndrome fetal hearts and embryonic hearts from a mouse model of Down syndrome. They identified a gene on human chromosome 21 called Dyrk1a, which causes heart defects when present in three copies in the mouse model of Down syndrome. An extra copy of Dyrk1a turned down the activity of genes required for cell division in the developing heart and the function of the mitochondria, correlating with a failure to correctly separate the chambers of the heart. A DYRK1A inhibitor partially reversed the genetic changes when tested on mice pregnant with pups that model the heart defects in Down syndrome.

Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome

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Published in Science Translational Medicine

Published

Immune cells images with help from the Crick's Light Microscopy STP.

Influx of water and salts propel immune cells through the body

Researchers at the Francis Crick Institute, working with Imperial College London, King’s College London and University of Cambridge, have shown that an influx of water and ions into immune cells allows them to migrate to where they’re needed in the body. The researchers imaged mouse T cells and observed that, following a chemokine signal, WNK1 is activated at the front of the cells, called the ‘leading edge’. The team showed that the activation of WNK1 opens channels on the leading edge, resulting in an influx of water and ions. They propose that this flow of water causes the cells to swell on the front side, creating space for the ‘actin cytoskeleton’ – the scaffolding inside the cell which holds its structure – to grow into. This propels the whole cell forwards and the process repeats again. The researchers believe that the mechanism they’ve discovered could be involved in lots of different cell types beyond immune cells.

T cell migration requires ion and water influx to regulate actin polymerization

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Published in Nature Communications

Published

Immune cells images with help from the Crick's Light Microscopy STP.

Researchers show genetic basis of facial changes in Down Syndrome

Researchers at the Francis Crick Institute, King’s College London and University College London have shed light on the genetics behind changes in the structure and shape of the face and head in a mouse model of Down Syndrome. The researchers found that having a third copy of the gene Dyrk1a and at least three other genes were responsible for these changes taking place in development – called craniofacial dysmorphology – which involve shortened back-to-front length and widened diameter of the head. Because Dyrk1a is so key for craniofacial dysmorphology, it's highly likely it's involved in other changes in Down Syndrome too, like heart conditions and cognitive impairment.

Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes

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Published in Development

Published

Microscope images of mouse and human spinal cord development at equivalent stages.

Species-specific pace of development is associated with differences in protein stability

Despite evolutionarily conservation of molecular mechanisms, the speed of development varies substantially between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the programme of motor neuron differentiation runs twice as fast in mouse as in human. We provide evidence that a two-fold increase in protein stability and cell cycle duration in human cells compared to mouse can account for the slower pace of human development, indicating that global differences in kinetic parameters play a major role in interspecies differences in developmental tempo. This study establishes a new experimental system in which to address fundamental questions.

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Published in Science

Published

Plasmodium-specific atypical memory B cells are short-lived activated B cells

This paper provides strong evidence that “atypical” B cells are short-lived activated B cells, and are probably the result of chronic stimulation and not the cause of chronic malaria. This questions the commonly held view that atypical B cells are evidence of an aberrant or defective response in malaria.

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Published in eLife

Published

WNK1 kinase balances T cell adhesion versus migration in vivo

In this study we identified the WNK1 kinase as a negative regulator of CD4+ T cell adhesion and a positive regulator of T cell migration. Furthermore, we showed that WNK1 controls migration through the OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter. This was an unexpected finding since WNK1 had been previously shown to regulate salt homeostasis in the kidney. Our study is the first to have implicated movement of Na+, K+ and Cl- ions in the regulation of T cell migration.

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Published in Nature Immunology

Published

Analysis of motor dysfunction in Down Syndrome reveals motor neuron degeneration

In this study we showed that the Dp1Tyb mouse model of DS has locomotor defects, mapped the causative genes to a 25-gene region and identified that Dyrk1a is one of these. Furthermore, we found an unexpected progressive loss of motor neurons in these mice and showed that a similar loss is seen in humans with DS.

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Published in PLOS Genetics

Published

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Research case studies 

Explore a selection of recent case studies that spotlight particular areas of research at the Crick.