Insight on Research


A new tool to study neural networks

Diagram to show how use of SiR allows permanent labelling, manipulation and genetic alterations of neural networks

Neural networks, circuits of neurons, are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that neural network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. Yet our ability to target and study specific neural networks remains limited. Until now Rabies virus, which can jump synapses, has been used to investigate neural networks.

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First atomic structures of Tau filaments from Alzheimer’s disease brain

Tau filament structures

Alzheimer’s disease, the most common neurodegenerative disease, is characterised by the formation of filamentous Tau protein inside nerve cells and amyloid-beta peptides outside cells.  Despite more than three decades of research into Tau filaments from a range of different neurodegenerative diseases, atomic structures were still lacking.

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First 3D structure of the complete human dynein

Process of dynein’s activation

Dyneins are a family of motor proteins that move along microtubules to transport various important cargos, including proteins and RNAs, to different parts of the cell and are crucial to correct cell function. Gradually, the structure of various components of dynein have been revealed.

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Dynamic structure of human DNA repair enzyme, ATM, revealed

Dynamic structures ATM graphic

The DNA in cells is constantly damaged by both internal activities of the cell and by external factors such as ionising radiation. In order to function correctly, this damage must be repaired, or if it cannot be repaired, the cell must be killed to prevent development of diseases such as cancer. The large protein kinase, ataxia-telangiectasia mutated (ATM), is a vital component of the cell’s DNA repair machinery.

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The key to GPCR-G protein selectivity

GPCR-G Protein key graphic

G protein-coupled receptors (GPCRs) form the largest family of membrane-protein receptors and drug targets. With over 800 different family members in humans, GPCRs regulate diverse intracellular signalling cascades in different cell types, tissues and organ systems. Whilst GPCRs sense a plethora of environmental stimuli, the appropriate cellular response is primarily triggered by binding to four major Gα protein families encoded by 16 human genes.

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Integral component of the Wnt enhancesome identified

Refined model of Wnt enhanceosome

The Wnt signalling pathway is an ancient cell communication pathway that has important roles in development and cancer. Wnt signals elicit context-dependent transcriptional responses by stabilising a cytoplasmic effector called beta-catenin. This controls the embryonic development of tissues and organs in all animals, from the most primitive ones all the way to humans.

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First complete 3D genome structure from individual mammalian cells

DNA in the nucleus is arranged into nucleosomes to produce an 11nm fibre which then intricately folds into high order assemblies. This nuclear organisation – the 3D arrangement of the genome within the nucleus – is critically linked to nuclear processes. Previously it has only been possible to analyse genome organisation across populations of cells.

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How astrocytes control circadian time-keeping in our principal body clock

Composite image of astrocytes & neurons of the SCN

The suprachiasmatic nucleus of the hypothalamus (SCN) is our principal “body clock”, controlling our daily (circadian) rhythms of physiology and behaviour that adapt us to the 24-hour cycle of day and night.  It ensures that numerous other local tissue clocks distributed across the body are in tune with each other and with the external light-dark cycle.

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New insights into how peptides became a part of the ancient RNA world

Peptides from the ribosome of T. thermophilus

In all present-day organisms, information encoded in DNA, the genetic material of the cell, is converted via an RNA intermediate into proteins, the molecular machines of the cell. However, evidence suggests that in a distant evolutionary past our single-celled ancestors used only RNA for both genetic information storage and metabolism. A cornerstone of this “RNA world” would have been an RNA able to replicate itself.

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The idiosyncratic ribosomes of mitochondria

The overall structure of the complete yeast mitoribosome

Mitochondria are organelles within eukaryotic cells that likely evolved from an ancient bacterium that was engulfed by a primordial eukaryote. Within mitochondria, mitochondrial ribosomes (mitoribosomes) synthesise a subset of essential proteins encoded by the mitochondrial genome.

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