Insight on Research


Activation of lysosomes allows worms to live longer and may protect against neurodegenerative diseases

Disease-causing proteins and lysosomes in the body of a worm.

Ageing is a growing problem for society, particularly because of the associated increased risk of developing disease. Understanding how we might be able to live healthier for longer is a key goal of medical research. The nematode worm C. elegans is a commonly used model for studying the changes that take place as animals age.

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Insights into how KAP1 silences viral origin DNA in our genomes

Crystal structure of KAP1

Our genome contains DNA from ancestral retroviral infections. These stretches of DNA are not usually harmful unless the cell’s normal ability to regulate them is lost, then their expression can potentially lead to disease. Yorgo Modis’ group, in the University of Cambridge Molecular Immunity Unit at the LMB, have solved the structure of a master regulator of integrated retroviral DNA, KAP1, providing mechanistic understanding into the function of KAP1 in silencing retroviral insertions.

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Functionalized graphene sheets on gold grids aid structure determination by electron cryo-microscopy

Scanning electron micrograph of a grid square.

With the ‘resolution revolution’ of recent years, it should in principle be possible to determine atomic resolution structures of any proteins using electron cryo-microscopy (cryo-EM). However, in practice, preparation of frozen samples that are suitable for high resolution imaging is a barrier to progress.

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A novel mode of RNA recognition based on structure not sequence

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

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

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

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

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

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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