Insight on Research


Speeding up cargo deliveries in the cell

dynein/dynactin/BICDR1 complex

Cytoplasmic dynein-1, a protein that transports cargos along microtubule tracks throughout the cell, binds to dynactin and cargo adaptor proteins to carry its cargos over long distances. Various cargos use different adaptors to recruit dynein for transport. Until now, it has not been clear whether all cargos recruit dynein in the same way and how different cargo adaptors act.

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Uncovering how alcohol-derived metabolites damage the genome of stem cells

Lack of the two-tier protection system leads to genomic instability and mutations in blood stem cells.

Previous work from KJ Patel’s group in the LMB’s PNAC Division revealed that aldehydes – such as acetaldehyde, a by-product of alcohol metabolism – can damage our DNA. Further research by the group showed that our cells are protected against these toxic aldehydes using a two-tier protection system: enzymes that remove these aldehydes (tier-1) and DNA repair that fixes the damage they cause (tier-2).

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New machinery for membrane protein insertion

Squalene synthase, a membrane protein, becomes mislocalised when EMC does not function.

The human genome encodes approximately 5000 membrane-embedded proteins that carry out many essential processes such as cell-to-cell communication, cell adhesion and intracellular trafficking. Almost all of these proteins are assembled at the endoplasmic reticulum (ER) by molecular machines that guide them into the membrane. Because these thousands of membrane proteins are highly diverse in size, shape and charge, different machines are needed for different types of membrane proteins.

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Trim-Away: powerful new tool for studying protein function

All the cells in our body contain thousands of proteins, molecular machines which carry out almost all biological processes that are essential for life. Many diseases, such as cancer and neurodegeneration, are caused when these protein machines go wrong. Thus it has been a long-term goal in science to characterise the functions of proteins within our cells.

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Spliceosome catalysis: the completed puzzle

RNA at the core of the spliceosome.

The spliceosome is a molecular machine that plays an important role in gene expression. It cuts non-coding sequences (introns) out of messenger RNA (mRNA) precursors, and stitches together the useful coding sequences (exons). The spliceosome performs this in two steps. First, the start of an intron is recognised, cut, and joined to a specific point in the middle of that intron, forming a lasso-like looped structure.

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Human wound healing is affected by the body clock

Internal body clocks, which time the length of a day in almost all organisms, control many aspects of human physiology and activity, from when we go to bed to when we perform best mentally and physically. Most importantly, these biological circadian clocks are in every single individual cell of our bodies, not just in the brain.

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New insights into ubiquitin phosphorylation and the development of early-onset Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative condition caused by the loss of dopaminergic neurons in the midbrain, which manifests clinically in the form of characteristic motor defects. Most PD cases are sporadic and found in people above the age of 60. However, roughly 10% of PD cases are autosomal recessive juvenile forms (AR-JP), causing early-onset PD.  It is known that mutations in PARK genes are responsible for this, but often a molecular explanation is lacking.

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The missing link between golgins and endosomal vesicles discovered

A model for the role of TBC1D23 as a link between the trans-Golgi network golgins and FAM21A of the WASH complex on endosome-derived vesicles.

Inside our cells there are many distinct membrane compartments – organelles – which carry out the different tasks that allow the cell to function. Each organelle is like a factory that requires a constant supply of raw materials to stay active. Small transport vesicles deliver this cargo of particular proteins and lipids to each organelle.

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Network control principles predict neuron function in the C. elegans connectome

Image of a nematode worm brain

The connectome of an animal is the comprehensive map, or wiring diagram, of all the neural connections in the brain. However, an important challenge is how to make sense of this information.  The nematode worm Caenorhabditis elegans, still the only animal for which the entire connectome has been described, illustrates the problem. Although it has only 302 neurons, these make thousands of connections.

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