Insight on Research


Understanding how TRIM21 is regulated during viral infection

During a viral infection, our immune system produces potent antiviral molecules which are hugely important for restoring us to health. However, if made at the wrong time these molecules can be damaging, leading to autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Our antiviral response must therefore be tightly controlled so that we are protected against infection but do not suffer from autoimmune disease.

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Reversing a decline in cellular transport in ageing nerve cells

Fruit fly wing

Ageing is characterised by a decline in function at both the cellular and organismal level and is the major risk factor for several neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. One of the key cellular processes that is affected during ageing is the transport system that nerve cells use to deliver components to different locations.

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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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