Insight on Research


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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Uncovering the structure of the serotonin receptor

G protein-coupled receptor

Scientists in Chris Tate’s group in the LMB’s Structural Studies Division have used cryo-electron microscopy to determine the structure of the serotonin receptor coupled to the heterotrimeric G protein Go, providing insights into how receptors bind specific G proteins.
Communication between cells throughout our bodies is vital for our health.

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Controlling actin polymerisation in clathrin mediated endocytosis

Clathrin mediated endocytosis

Work from Harvey McMahon’s group in the LMB’s Neurobiology Division has uncovered how a protein, FCHSD2, controls actin polymerisation during endocytosis. Importantly the scientists discovered that FCHSD2 does its job from the area surrounding the site of endocytosis – making it the first description of an endocytic protein which localises to the flat region around endocytic events.

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Parkin activation and early-onset Parkinson’s disease: the last piece of the puzzle

The structure of activated phospho-Parkin bound to phospho-ubiquitin

Researchers at the LMB have solved the elusive 3D structure of activated Parkin, an enzyme implicated in early-onset Parkinson’s disease. Led by David Komander’s group in the LMB’s PNAC Division, in collaboration with the LMB’s Biological Mass Spectrometry facility, this new work reveals insights into previously unstudied parts of this important protein and helps explain why families with certain mutations in Parkin suffer from early-onset Parkinson’s disease.

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How does the replisome respond to DNA damage?

Diagram to illustrate replication of damaged DNA in a test tube

Work by Joe Yeeles’ group in the LMB’s PNAC Division has for the first time revealed the earliest responses when the eukaryotic DNA replication machinery, the replisome, collides with DNA damage.
Every time a cell divides, its DNA must be replicated so that each daughter cell inherits a complete copy of the genome.

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HIV exploits a native cellular molecule to increase the stability of its capsid

IP6 anchors the HIV capsid

Scientists in Leo James’ group in the LMB’s PNAC Division, in collaboration with Till Böcking’s group at the University of New South Wales, Australia and Adolfo Saiardi’s group at the MRC Laboratory for Molecular Cell Biology, have uncovered how the HIV virus stabilises its capsid by binding to an abundant cellular polyanion, IP6.

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