Insight on Research


How the brain orchestrates head movement

Mouse playing motor notes on collicular piano

While reaching for our morning cup of coffee, we experience the movement of our arm as continuous and smooth. It is natural then to think that the representation of these movements in our brain would also be continuous and smooth. Studying how such target-oriented movements are controlled, Marco Tripodi’s group in the LMB’s Neurobiology Division reveal for the first time that the representation of these actions in the brain is instead granular and discontinuous.

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New cell death pathway in tuberculosis indicates potential use of commonly used drugs

Ruptured infected macrophages (in green) and mycobacteria (in magenta) growing extracellularly

Macrophages are a critical part of our immune system. They patrol our tissues, and when they encounter debris or invaders such as bacteria and parasites, they engulf the particles and destroy them. But if, in the course of tuberculosis, these infected macrophages die through a process called necrosis, in which the cells burst open, then the engulfed bacteria are released back into the extracellular environment where they can grow unrestricted.

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Characterisation of recombinant human proteasome complexes

The human 20S-PA200 proteasome assembly

Proteasomes are the main protein recycling centres in all eukaryotic cells. Apart from their role in maintaining a healthy protein population, these complex molecules are critical as they also control key signals that determine the onset of crucial cellular events, including cell division. However, proteasomes are difficult to study. There are many different proteasome forms in a cell, which are difficult to separate biochemically.

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Germ cells need DNA crosslink repair to develop normally

Germ cell development threatens genetic integrity

Germ cells face a significant threat to their genetic integrity during embryonic development. Ross Hill and Gerry Crossan, of the Crossan Group in the LMB’s PNAC Division, have recently found that these cells need a specific form of DNA repair, known as crosslink repair, in order to develop normally. The findings have been published online in Nature Genetics on July 31, 2019.
Germ cells (sperm and eggs) constitute the pipeline that passes on the genetic instructions to make a new organism.

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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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