Insight on Research


Major breakthrough identifies cause and treatment of fatal autoimmune disease

Graphical depiction of symptoms of ORAS (OTULIN-related Autoinflammatory Syndrome)

The cause of a potentially fatal inherited autoimmune disease has been identified for the first time. The disease, now named OTULIN-related autoinflammatory syndrome (ORAS), was discovered by doctors treating patients who developed symptoms such as rashes, fever, and diarrhoea shortly after birth. The immune system of these patients spontaneously activates and starts to attack the patient’s own body leading to the described symptoms and eventually to the child’s death.

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Molecular basis of APC/C regulation by the spindle assembly checkpoint

During eukaryotic cell division (mitosis) the cell’s chromosomes are duplicated and then equally separated into two new daughter cells. To prevent errors in mitosis cells employ checkpoints that monitor and coordinate the correct order of events. Checkpoints either delay cell division, or if unrecoverable, cause cell death.

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HIV uses capsid pores to import nucleotides and evade innate immunity

HIV is a retrovirus, meaning it has to copy its RNA genome into DNA in order to infect cells. While much has been learned about the virus, investigators don’t understand how it evades our immune system so successfully. A long-standing question has been how the HIV virus copies its genome using raw materials from the cell without being detected by immune sensors.

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An evolutionarily conserved pathway controls proteasome homeostasis

Cell survival depends on adaptive signalling pathways to ensure that the supply of vital components matches the fluctuating needs of the cell. The proteasome is essential for the selective degradation of most cellular proteins and thereby controls virtually all cellular processes. The current prevailing view is that protein degradation is largely regulated at the level of ubiquitination.

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Structure of the catalytic spliceosome

model of spliceosome structure

The spliceosome is a molecular machine, which together with RNA polymerases and ribosomes plays a critical role in basic gene expression. Due to its highly dynamic nature the structure of the spliceosome has remained elusive until now. Research by Kiyoshi Nagai’s group, in the LMB’s Structural Studies Division, has for the first time captured the spliceosome in a fully active, substrate-bound state, immediately after first catalytic reaction.

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NBLAST – a new online tool to compare neurons

Researchers in Greg Jefferis’s group in the LMB’s Neurobiology Division have developed a new online tool to analyse images of neurons. This tool, known as NBLAST, is free and available to all. NBLAST enables researchers to measure the similarity between neurons and organise them into neuron families, akin to tools such as BLAST that allow protein sequences to be compared.
Neuroscience is seeing a period of major growth in the structural characterisation of neurons.

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In vivo visualisation and quantification of the circadian clock protein Period2

Circadian clocks are found across all higher species, controlling daily rhythms of behaviour and physiology. They are thought to “tick” by producing and then degrading circadian proteins on a 24 hour cycle. At a molecular level, they typically involve expression of “clock” genes that are inhibited approximately every 24 hours by the proteins they encode.

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A protein quality control system for mislocalised proteins

Ubiquilins (green) and Huntington’s disease aggregates (red) in a cell

In order to function properly, many of the cell’s proteins need to be segregated to membrane-bound organelles and assembled into multi-protein complexes. Newly made proteins that fail to be localised or assembled properly must be promptly recognised by the cell and destroyed. These pathways of protein quality control are important because the accumulation of aberrant proteins can lead to neurodegeneration and various other diseases.

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Development of effective immunity to infections is promoted by chromatin component

Effective immunity to infections requires the development of a diverse repertoire of antibodies. Antibody diversity is created through a process known as somatic hypermutation, which is the programmed mutation of specific sequences of DNA in the antibody genes. The introduction of mutations results in the production of antibodies that recognise and bind to different antigens, such as microbes, and allows the immune system to adapt as it is exposed to new antigens.

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Insight into the complex 3D topology of the TOR enzyme

Diagram of a TOR protein complex

Target of Rapamycin (TOR) is a protein kinase that is essential in maintaining cellular homeostasis. In mammalian cells the enzyme occurs as two large protein complexes and one of these, mTORC1, controls growth of cells by integrating signals from growth factors and the nutritional state of cells. Many tumours in humans are associated with inappropriate regulation of this protein complex, and it has been demonstrated to be an important therapeutic target for cancer and autoimmune disorders.

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