Insight on Research


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

One of the major roles of a skin cell is to respond to and heal wounds, such as cuts and scratches. Skin cells do this by moving into the damaged area, where they produce restorative proteins such as collagen. The ability of cells to migrate into wounds depends on an essential protein called actin. Research led by Nathaniel Hoyle in John’s group showed that the circadian clock ensures that actin in human skin cells is more active during the daytime than at night.

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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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How the poly(A) tail is added to the end of mRNAs

polymerase module structure

Genes are encoded in DNA and need to be copied into an intermediate mRNA molecule that contains the instructions to allow synthesis of protein. Almost every mRNA has a repetitive sequence at one end called a poly(A) tail. The length of this tail specifies the amount of time that the mRNA is present in the cell, and how often it is translated into protein. Errors or changes in the tail are found in human diseases including β-thalassemia, thrombophilia and cancer, as well as viral infections.

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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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Folate and formaldehyde: from vitamin to genotoxin to DNA building block

Cell growth requires the synthesis of molecules, such as nucleotides to make DNA and amino acids to make proteins. One essential building block of these is the one carbon unit. This is produced by the one carbon (1C) cycle, which requires the vitamin folate and the amino acid serine (the main source of the 1C unit). 1C metabolism is important for human health, and folate deficiency causes birth defects, nerve damage and anaemia.

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Amino acid homorepeats influence the function and evolution of proteins

A section of a protein containing an amino acid homorepeat.

Amino acids are the building blocks of proteins. Just twenty different amino acids are strung together in different orders – like beads – to build all the proteins in living organisms. When a single type of amino acid is found consecutively within a protein, this is known as a homorepeat. Abnormal variation in the length of amino acid homorepeats has long been known to be associated with disease, such as Huntington’s.

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Mechanism for cleaning up leftover proteins

Clearing up leftover parts of a complex machine

The cells in our body contain numerous molecular machines that carry out nearly all biological processes essential for life. These machines are built from proteins that are often assembled into complex structures. For example ribosomes contain 80 distinct proteins on a scaffold of four different RNAs. The assembly of such structures from so many parts is a complicated process and inevitably results in ‘leftover’ proteins.

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