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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.

Fly wing growth

Oxygen availability constrains growth during development

Growth is a key feature of development, but animals, organs and tissues must know when to stop growing. Researchers at the Crick have shown that the sac-like structures that give rise to fly wings do not stop growing abruptly. Instead, growth slows down over the course of days. Measurements of global gene activity during growth deceleration suggest that, as the primordium expands, it becomes increasingly hypoxic. Decreasing oxygen availability, perhaps due to inefficient import as tissue size increases, was confirmed with new genetic sensors of cellular oxygen. This study uncovers a feedback loop whereby growth (and increasing tissue size) leads to hypoxia, which in turn dampens growth to ensure that oxygen demand does not overwhelm dwindling supplies.

HIF-1α-mediated feedback prevents TOR signalling from depleting oxygen supply and triggering stress during normal development

Published in Nature Communications

Published

firebrat and fruit fly

When evolution took flight

Researchers at the Crick have identified a signalling feedback loop which they think may have been vital to the evolution of insect wings and therefore flight. They found that, as concentrations of a morphogen called Dpp decrease across the wing tissue, another molecule called Brinker forms a reverse gradient. The Brinker gene is repressed by Dpp and is therefore increasingly expressed as the Dpp signal becomes weaker. They then found that Brinker is only found in insects and not in closely related crustaceans, and that it is found in a wingless insect called a firebrat, but doesn't form a gradient and is as yet unconnected to the Dpp signal transduction. This suggests that the Brinker-mediated feedback circuit may have been an evolutionary innovation of winged insects.

A genetic circuit that extends the useful range of a BMP morphogen arose alongside insect wing evolution

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Published in Current Biology

Published

Fly wings

Refining wing vein pattern on the fly

During development, cells acquire cell fates with remarkable precision and reliability. This is exemplified in insect wings, which form a highly stereotypical vein pattern. Molecular markers suggest that vein fates are specified during larval stages, when wing primordia still undergo growth and morphogenetic movements. Previous work has shown that the initial vein pattern can be compared to broad brush strokes that are subsequently refined to make up the final picture. Using live reporters of cell fate and signalling activity, combined with mathematical modelling, researchers at the Crick and the University of Geneva show how a network of three well-known signal transduction pathways continuously update the vein fate to ensure reproducible vein formation despite the complex flows associated with tissue rearrangements.

Signaling-dependent refinement of cell fate choice during tissue remodeling in Drosophila pupal wings

Published in Developmental Cell

Published

epithelial cells

Ecdysone, key Drosophila steroid hormone, both initiates and stops cell growth depending on level in the circulation

In this paper, the researchers show that a key steroid hormone of the fruit fly Drosophila, Ecdysone, both initiates and stops cell growth, depending on its level in the circulation. Low level Ecdysone promotes cell growth by removing a default anti-growth role of its receptor, while high levels trigger instructions from genes that stop cells from growing. The researchers then show mathematically and with synthetic reporters that combinations of basic gene regulatory elements can replicate the dual activity of this hormone. They highlighted the concentration of nuclear hormone signalling needed for growth control, which could be of interest for further research into growth hormone signalling for therapeutic purposes.

The Drosophila ecdysone receptor promotes or suppresses proliferation according to ligand level

Published in Developmental Cell

Published

New tool to control of fruit fly gene expression using light

Researchers in the Vincent Lab, , in collaboration with the group of Yohanns Bellaiche at Institut Curie in Paris, have developed a new tool for robust control of gene expression in Drosophila using light. They successfully used the new method to activate key genes in different tissues and at various developmental stages and demonstrated gain and loss-of-function phenotypes at animal, organ, and cellular levels. Their work provides developmental biologists with the ability to control gene expression with high temporal and spatial resolution, a valuable addition to the Drosophila genetic toolkit.

Rapid and robust optogenetic control of gene expression in Drosophila

Published in Developmental Cell

Published

Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition

In this paper, we uncover the cell biological basis of a human ribosomopathy. Somewhat unusually, this project was spurred by a member of the public who asked us to create a Drosophila model of his son’s condition caused by a ribosomal mutation (RPS23[R67K]. Flies carrying this mutation are viable but display many markers of cellular stress. Surprisingly, this is not caused by insufficient protein synthesis capacity but instead by a reduced ability to eliminate misfolded proteins, perhaps because of an unusual burden from orphaned ribosomal proteins. We found that pharmacological or genetic inhibition of TOR significantly rescued cellular stress in these animals, suggesting a therapeutic strategy to alleviate the symptoms of this and other ribosomopathies.

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Published in Nature Cell Biology

Published

Glypicans shield the Wnt lipid moiety to enable signalling at a distance

This paper solves the Wnt solubility problem, which has preoccupied the Wnt field for the past 15 years. It explains how the lipid of Wnts can be maintained in the extracellular space.

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Published in Nature

Published

Patterning and growth control in vivo by an engineered GFP gradient

By merging the power of molecular genetics, basic physical chemistry and mathematical modeling we show quantitatively how an inert protein, GFP, can be turned into a morphogen that provides positional information in a developing tissue, the Drosophila wing disc. This is the first time that an active synthetic morphogen gradient has been reconstituted in vivo. Because the properties of the synthetic gradient can be experimentally modulated, a physical analysis of molecular determinants of morphogen gradients becomes possible.

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Published in Science

Published

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Research case studies 

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