Insight on Research


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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Daily magnesium fluxes regulate cellular timekeeping and energy balance

stylised 24 hour clock showing release and uptake of magnesium during the night and day

Most organisms, including humans and plants, have circadian rhythms that allow them to adjust their metabolism and behaviour to match the 24-hour cycle of day and night. Circadian rhythms are even observed at the level of individual cells, and are dependent upon a biological clock mechanism that is not fully understood.

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Nanostructures from synthetic genetic polymers

3D model from EM data of an octahedral nanostructure composed entirely of an artificial XNA polymer

‘Synthetic biology’ is a scientific approach that seeks to answer fundamental questions in biology by reconstruction and modification of the molecules and processes of life. Beyond its well-known role as the carrier of genetic information, DNA (and its close cousin RNA) have shown great promise as a nano-molecular building material: by careful arrangement of the bases A, T, C and G, DNA strands can be programmed to fold into specific 3D shapes.

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Structure of brain receptor linked to learning

Structure GluA2/3 AMPA receptor heteromer top view

Information transfer in the nervous system occurs at synapses, where presynaptic signals are interpreted by postsynaptic receptors. Ingo Greger’s group, in the LMB’s Neurobiology Division, study this process with a focus on AMPA-type glutamate receptors (AMPARs) at various levels of complexity. AMPARs are the prime mediators of excitatory neurotransmission and are regulators of synaptic plasticity, which underlies learning.

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