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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.

Mouse brain slice

Hunger influences the behaviour of female mice towards pups

Researchers at the Crick have found that hunger can make virgin female mice aggressive towards pups, but only in certain hormonal states. These mice would usually ignore other females' pups or show parent-like caring behaviour. The team found that AgRP neurons mediated the effect of food deprivation on behaviour towards pups, by targeting the medial preoptic area. Mice at certain stages of the reproductive estrous cycle were more likely to become aggressive towards pups, dictated by the ratio of oestradiol and progesterone setting the responsiveness of MPOA neurons. They showed that hunger information carried by the AgRP neurons dampens neuronal activity in the MPOA, stimulating the switch from caring behaviour to pup-directed aggression. 

Integration of hunger and hormonal state gates infant-directed aggression

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Published in Nature

Published

Yellow background with black disc in the centre containing small white organoids

Building a backbone: scientists recreate the body’s ‘GPS system’ in the lab

Scientists at the Crick have generated human stem cell models which, for the first time, contain notochord – a tissue in the developing embryo that acts like a navigation system, directing cells where to build the spine and nervous system (the trunk). The team first analysed chicken embryos to understand exactly how the notochord forms naturally. By comparing this with existing published information from mouse and monkey embryos, they established the timing and sequence of the molecular signals needed to create notochord tissue. With this blueprint, they produced a precise sequence of chemical signals and used this to coax human stem cells into forming a notochord. The stem cells formed a miniature ‘trunk-like’ structure, which spontaneously elongated to 1-2 millimetres in length. The scientists believe this work could help to study birth defects affecting the spine and spinal cord.

Timely TGFβ signalling inhibition induces notochord

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Published in Nature

Published

DNA damage in mouse embryonic stem cells.

Radiation or genotoxic drugs do not activate cGAS-STING signalling

Researchers at the Crick investigated cGAS-STING, a pathway that evolved to sense cytoplasmic DNA following bacterial or viral infection, triggering an immune response. They used ionising radiation or genotoxic compounds to damage nuclear DNA, which then formed micronuclei - small compartments that encapsulate the damaged DNA in the cytoplasm. The researchers found that micronuclei induced by radiation failed to activate cGAS-STING signalling, as did genotoxic compounds such as reversine and hydroxyurea. This was due to the presence of histones in the micronuclei that package DNA into chromatin, which inhibits activation of the cGAS-STING pathway. This research challenges the notion that all cytosolic DNA in micronuclei activates cGAS-STING and suggests potential limitations for using genotoxic drugs to stimulate the immune system in cancer therapy.

Micronuclei induced by radiation, replication stress, or chromosome segregation errors do not activate cGAS-STING

Published in Molecular Cell

Published

A 'spiny' neuron - with lots of spines showing lots of connections with other neurons - in the pregnant mouse brain.

Mouse brain is ‘rewired’ during pregnancy to prepare for motherhood

Researchers at the Francis Crick Institute have shown that pregnancy hormones ‘rewire’ the brain to prepare mice for motherhood. Their findings show that both oestrogen and progesterone act on a small population of neurons in the brain to switch on parental behaviour even before offspring arrive. These adaptations resulted in stronger and more selective responses to pups. They found that a population of nerve cells (galanin-expressing neurons) in an area of the brain called the medial preoptic area (MPOA) in the hypothalamus, associated with parenting, was impacted by oestrogen and progesterone. Brain recordings showed that oestrogen simultaneously reduced the baseline activity of these neurons and made them more excitable, whereas progesterone rewired their inputs, by recruiting more synapses (sites of communication between neurons. Making these neurons insensitive to hormones completely removed the onset of parental behaviour during pregnancy.

Hormone-mediated neural remodeling orchestrates parenting onset during pregnancy

Published in Science

Published

Modular microfluidics enables kinetic insight from time-resolved cryo-EM

Cryo-EM has the potential to study any native conformation of a macromolecule. However, the sample preparation time is high, compared to the timescale of most protein interactions and conformational changes. In this paper, we established a robust method of time-resolved cryo-EM sample preparation. We produced high-quality samples for microscopy while speeding up the process of making them by several orders of magnitude. This allowed samples to be collected within 30ms of the initiation of a biochemical reaction, within the timeframe of many critically important and interesting processes. This enables a whole new class of experiments in structural biology research.

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Published in Nature Communications

Published

Cellular geometry scaling ensures robust division site positioning

Here we describe our discovery that preservation of specific cellular geometry across a range of cell sizes is essential for correct division site positioning and survival, demonstrating the organismal-level function for scaling.

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Published in Nature Communications

Published

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Research case studies 

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