Insight on Research


Cerebral organoids at the air-liquid interface generate nerve tracts with functional output

An improved brain organoid cultured at the air-liquid interface showing aligned nerve bundles, colour-coded by their orientation.

Cerebral organoids, also sometimes called mini-brains or brain organoids, have become an important and useful tool in understanding human brain development and disease. They have the potential to model brain functions, such as information transfer between neurons, but restrictions in their growth have so far limited this. Now, Madeline Lancaster’s group in the LMB’s Cell Biology Division, have for the first time demonstrated that cerebral organoids can direct muscle movement.

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Architecture of a prominent neurotransmitter receptor involved in memory formation and learning revealed

AMPA receptor with GluA1 (blue) and GluA2 (red) subunits and TARP γ8 auxiliary subunit. Binding of the neurotransmitter glutamate will allow the pore to open and sodium ions to flow into the neuron

AMPA receptors are among the most commonly found receptor in the nervous system and play an important role during memory formation and learning. They are composed of four subunits with various possible combinations. Although AMPA receptors act predominantly as heteromeric complexes, structural studies to date have focused on assemblies made from four copies of the same subunit.

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How detection of an invading Salmonella bacterium leads to formation of autophagosomes

Salmonella that enter the cytosol of epithelial cells are targeted by both the autophagy cargo receptor NDP52 (red) and the autophagy regulator FIP200 (green).

Most historical research on immunity has focused on the dedicated cells of our immune system, but, ever since the first single-celled organisms evolved, cells have had to defend themselves against infection. Thus we have a more ancient form of cellular immunity, termed xenophagy, that allows cells throughout our body to capture bacteria that have invaded their cytosol and degrade those invaders inside specialised vesicles termed autophagosomes.

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Identification of a potential therapeutic target in colorectal cancer initiation

Tumour in mouse intestinal epithelium

Colorectal cancer is one of the most common cancers in the UK. Virtually all colorectal cancers are initiated by hyperactive signalling through the Wnt/β-catenin pathway. This can occur due to activating mutations in the protein β-catenin or inactivation of Adenomatous Polyposis Coli (APC), a protein that normally drives degradation of β-catenin.

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Engineering dynein to move backwards to understand how it moves forwards

A cryo-EM class average of single dynein molecules bound to microtubules

Dyneins are a family of motor proteins that run along the microtubule tracks that make up the cytoskeleton. They drive beating of cilia/flagellar and transport of cargos, contributing to processes such as clearing mucus, allowing sperm to swim, positioning organelles and clearing up misfolded proteins. All members of the family move along microtubules in the same direction, but it was not known why this is the case.

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Cutting-edge microscopy reveals how apoptosis starts in the mitochondria

3D model of a mitochondrion during apoptosis in human cells

Apoptosis is a highly controlled form of cell death important for cell turnover during life, in embryonic development, including separation of fingers and toes, and as a cellular response against cancer. Although mitochondria are more widely known for their role as the energy-generating “powerhouses” of the cell, they also have an important role in initiating apoptosis: rupture of the mitochondria releases factors that contribute to an accelerating cascade towards cell death.

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A master regulator of cell movement in response to chemical signals

Dictyostelium discoideum cells

Movement of cells is vital during processes such as wound healing and development. Where cells move is usually controlled by gradients of chemicals in the environment that guide them to particular destinations. These attractive chemicals, or chemoattractants, are detected by receptors on the cell surface, which signal to the cytoskeleton to control movement in the appropriate direction.

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Structure of a post-catalytic human spliceosome improves understanding of splicing control

The structure of the human post-catalytic spliceosome reveals novel proteins that promote mRNA formation

Although humans have a similar number of genes as flies, part of our greater complexity comes from a process called alternative splicing, in which multiple different variants of proteins can be made from a single gene. This process is controlled by a molecular machine called the spliceosome. Until recently, much of the work on spliceosomes has been done using yeast spliceosomes as this system is well conserved and works very similarly across all eukaryotes.

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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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