Insight on Research


The structure of retromer: a molecular machine packing cargo at the cell’s logistics hub

Artistic blueprint of a slice through a retromer-coated membrane tubule. Retromer forms arches around the surface of the tube.

Internal transport between different cellular compartments is a complicated process requiring formation of transport carriers, and sorting the right cargo into those carriers, for delivery to the correct part of the cell. Retromer is a protein complex that forms transport carriers departing from the cell’s central sorting station, the endosome. The architecture of the complex and how it contributes to carrier formation and cargo sorting was unknown.

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How cells selectively enhance gene expression in response to stress

Yeast cells under stress

Cells need to respond quickly when they encounter stress conditions in order to avoid consequences such as cell death. New research from Madan Babu’s group in the LMB’s Structural Studies Division has identified a mechanism by which cells can enhance the expression of stress-response genes by increasing the efficiency of protein synthesis specifically for these genes.

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Tau filament structures differ between neurodegenerative diseases

Narrow Pick filaments.

Michel Goedert’s group in the LMB’s Neurobiology Division and Sjors Scheres’ group in the LMB’s Structural Studies Division have used cryo-electron microscopy (cryo-EM) to solve the structures of tau filaments from patients with the frontotemporal dementia Pick’s disease.

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How neuropeptide signalling controls sensitisation in response to touch in C. elegans

C. elegans co-labelled with markers for neurotransmitter and neuropeptide receptor expression.

When an animal detects a stimulus that might signal danger, this primes sensory and motor organs to respond more readily to further stimulation. This is called sensitisation and is one aspect of the more general phenomenon of arousal, in which animals become more alert and can respond more effectively to potential threats. However, the basic principles of how arousal is triggered have not been fully understood.

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How flat sheets of cells become tubular organs: observing cellular dynamics from 2D to 3D

Embryo salivary gland development

Many complex tubular organs, including kidney, lung, the intestine and several glands, form from a flat layer of cells during animal development. Failure of proper tube formation underlies severe congenital malformations such as Spina Bifida, and the failure to maintain tube architecture for instance underlies Polycystic Kidney Diseases. How tissues transition from flat 2D structures to 3D tubes is poorly understood.

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Scientists identify exoplanets where life could develop as it did on Earth

An artist's concept of Kepler-452b, a 1.5 Earth size exoplanet discovered within the habitable zone of a Sun-like star.

Scientists have identified planets outside our solar system where the same chemical conditions exist that may have led to life on Earth. The researchers, from John Sutherland’s group in the LMB’s PNAC Division and the University of Cambridge Cavendish Laboratory, found that the chances for life to develop on the surface of a rocky planet like Earth are connected to the type and strength of light given off by its host star.

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Making the undruggable druggable: the first platform to discover selective phosphatase inhibitors

New method identifies a selective inhibitor of PPP1R15B, a potential target for Huntington’s disease

Anne Bertolotti’s group in the LMB’s Neurobiology Division have developed the first platform to discover selective inhibitors of phosphatases, a class of enzyme which have largely been considered ‘undruggable’. This has allowed Anne’s group to identify a small molecule, Raphin1, which selectively inhibits a protein phosphatase and is effective in a mouse model of Huntington’s disease – an exciting step in the potential treatment of neurodegenerative diseases.

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Cryo-electron microscopy reveals near-atomic resolution structure of the prespliceosome

Two alternative splicing factors

Kiyoshi Nagai’s group in the LMB’s Structural Studies Division have used electron cryo-microscopy to solve the structure of the prespliceosome at near-atomic resolution, providing new insights into how the spliceosome is assembled and regulated.
The human genome contains approximately 20,000 genes, which when transcribed produce precursor messenger RNA (pre-mRNA) consisting of coding sequences (exons) and non-coding sequences (introns).

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Discovering how translation and mRNA decay are linked

Gel showing global poly(A) tail lengths which shorten over time

Scientists in Lori Passmore’s group in the LMB’s Structural Studies Division have revealed new mechanistic insights into the link between translation and mRNA decay.

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