Insight on Research


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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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 electron cryo-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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