Insight on Research


Redefining the importance of astrocytes in the brain’s master body clock

A body clock puppet is moved around the clock by puppeteers representing astrocyte- and neuron-driven control

Our daily cycle of sleep and wakefulness – our circadian rhythm – is controlled by a central master clock in our brains: the suprachiasmatic nucleus (SCN). Previously, Michael Hastings’ group in the LMB’s Neurobiology Division had demonstrated that astrocytes were not merely the supporting cells that they had been thought to be, but also had a role in driving the body clock alongside the approximately 10,000 neurons found in the SCN.

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Structures of the human GABAA receptor reveal how it functions and could help improve key drugs

Structure of the human 132 GABAA receptor in a lipid nanodisc

Practically all brain functions are controlled through a finely tuned balance of neuronal excitation and inhibition. The main inhibitory neurotransmitter in vertebrates is gamma-aminobutyric acid (GABA). GABA signals through two types of cell surface receptors: GABAA and GABAB, with GABAA receptors mediating millisecond-fast neurotransmission and GABAB receptors mediating slower signalling events.

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Catching enzymes in the act of making an antibiotic

Artist’s view of the thioesterase domain of Vlm2TE with trapped valinomycin in its active site

Enzymes are proteins that accelerate the conversion of substrate molecules into product molecules. Many enzymes accelerate reactions through formation of chemical bonds to their substrates, but the complexes formed this way are difficult to characterise, as they are intrinsically short-lived.

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Making a cell-based factory for polymer synthesis

Researchers in Jason Chin’s group in the LMB’s PNAC Division have for the first time engineered and optimised a ‘stapled’ ribosome that can act as a cell-based factory for synthetic protein polymer synthesis.
We are familiar with polymers in everyday life, from nylon to kevlar and plastics.  Polymers are composed of chemical compounds strung together like beads in a necklace.

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A new tool using genetic code expansion to study circadian rhythms

Controlling the body clock with an expanded genetic code

Circadian rhythms dominate our lives through our daily cycle of sleep and wakefulness. These rhythms are controlled by a master clock in the brain: the suprachiasmatic nucleus (SCN). Studying neuronal cell biology and how the SCN drives behaviour in humans and all animals has been made easier by the development of tools that allow rapid, reversible, and conditional control of these systems.

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How replication of DNA is initiated at origins

Mapping start sites for DNA replication

We each replicate billions of metres of DNA every hour in our dividing cells and it is important that this DNA is replicated accurately. This requires a complex set of machinery called the replisome to unwind the paired strands of DNA allowing different polymerase enzymes to produce new copies. DNA replication is further complicated by the antiparallel structure of DNA: the two strands run in opposite directions alongside one another, and DNA polymerases can only function in one direction.

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New insight into how membrane proteins are made

Endoplasmic Reticulum

The human genome encodes thousands of proteins that are embedded in the membranes of all cells. These membrane proteins have numerous functions ranging from ion transport, to cell communication, to sensing odours, and others. In order to carry out these functions, they must be precisely oriented, folded, and assembled correctly.

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Discovery of a sensor for ribosome collisions

Structure of two collided ribosomes

A collaborative team from the LMB’s Cell Biology and Structural Studies Divisions has identified a cellular factor that detects ribosome collisions. The ribosome is the molecular machine responsible for reading the genetic code to produce proteins, a process known as translation. Such collisions between ribosomes are a sign that something has gone awry during translation, and the collision-detecting factor is critical for initiating pathways to resolve the problem.

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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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