Insight on Research


A novel mode of RNA recognition based on structure not sequence

Structure of the Pan2 deadenylase enzyme bound to a poly(A) RNA

Our genetic code is translated from DNA into proteins through an intermediate molecule: messenger RNA (mRNA). One major way in which synthesis of proteins can be regulated is through turnover of mRNA; less protein is produced from a short-lived mRNA molecule. The signal for the degradation of a particular mRNA is the removal of a stretch of adenosines (As) at the end of the molecule, known as the poly(A) tail.

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Creating an entire bacterial genome with a compressed genetic code

Computational design of an entire bacterial genome with a compressed genetic code

Jason Chin’s group in the LMB’s PNAC Division have, for the first time, synthesised the entire genome of a commonly used model organism, the bacterium E. coli. There has only been one previous example of synthesis of an entire genome: for the Mycoplasma bacterial genome, which consists of approximately 1 million bases. Over the last 5 years, Jason’s group have developed a robust method for assembly of large pieces of synthetic DNA. This has enabled them to synthesise the entire E.

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How tighter ligand binding in drug target cell-surface receptors is achieved

Structure of the active state of the beta1-adrenoceptor bound to salbutamol

Much of the communication in cells is dependent on the presence of cell-surface receptors that detect signals in the form of messenger molecules called ligands. One large family of receptors are G protein-coupled receptors (GPCRs). This family includes a number of important drug targets, so understanding their structure and function are important. Their name derives from the fact that the receptor must couple with a G protein in order to function.

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How eating feeds into the body clock

Eating at the wrong time causes increased levels of insulin to disrupt the body clock contributing to the adverse effects of shift-work on health

We are regularly reminded that a balanced diet is key to staying healthy and preventing disease. What is less well known is that the time at which we eat may also be an essential to long-term health.
Central to this are circadian rhythms – commonly referred to as ‘body clocks’. These are endogenous daily rhythms that occur in every cell of the body; affecting a wide range of physiological processes, from when we sleep, to hormone levels, to how quickly we metabolise drugs.

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Uncharged DNA-like molecules can store genetic information and function like antibodies

Two strands of DNA paired together (left) and a novel uncharged DNA-like molecule paired with a strand of DNA (right)

DNA and RNA both have a highly negatively charged backbone and it was widely believed that such a charged structure is essential for their function as information storage molecules. Philipp Holliger’s group, in the LMB’s PNAC Division, in collaboration with researchers at NIH in the USA and at IRB in Barcelona, have challenged this conjecture by producing a DNA-like genetic polymer that is both uncharged and can store and transfer genetic information.

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Snapshot of a pre-catalytic spliceosome reveals how the exon-intron junction is introduced into the active site

Structure of a human spliceosome before 5’ splice site transfer

The process of reading the genetic code of DNA to produce proteins involves an intermediate molecule called messenger RNA (mRNA). Initially mRNA contains sequences that won’t form part of the new protein, termed introns, as well as protein-coding sequences known as exons. Removal of introns and joining together of exons is called splicing and is performed by the spliceosome, a large molecular machine in eukaryotes that plays an essential role in the control of gene expression.

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Prebiotic chemistry shows how DNA building blocks might have arisen at the origin of life

DNA comes into the Light

Life is based around a complex system of information storage in DNA and conversion of that information into the RNA and proteins that perform the functions to allow our cells and us to survive. Understanding the origin of life requires identification of plausible mechanisms by which the chemical building blocks of this system might have arisen on early Earth.

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New tau structures may benefit diagnosis and treatment of head injury-associated neurodegeneration

A novel tau filament fold was identified in chronic traumatic encephalopathy (one former American footballer and two ex-boxers).

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repeated blows to the head, particularly in relation to contact sports, such as American football and boxing. Understanding of the disease is limited and there is no available treatment. Definitive diagnosis currently depends on examination of the brain after death.

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Cerebral organoids at the air-liquid interface generate nerve tracts with functional output

An improved brain organoid cultured at the air-liquid interface showing aligned nerve bundles, colour-coded by their orientation.

Cerebral organoids, also sometimes called mini-brains or brain organoids, have become an important and useful tool in understanding human brain development and disease. They have the potential to model brain functions, such as information transfer between neurons, but restrictions in their growth have so far limited this. Now, Madeline Lancaster’s group in the LMB’s Cell Biology Division, have for the first time demonstrated that cerebral organoids can direct muscle movement.

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