Insight on Research


Fast, simple, accessible and affordable: The future of cryo-EM

A 3D reconstruction of hepatitis B virus capsid at 100 keV

Demonstration of a new direction in electron cryo-microscopy at the LMB promises a new era in resolving biological structures
Is it possible to improve imaging of purified biological specimens in electron cryo-microscopy (cryo-EM) while also reducing its cost? The latest proof-of-principle paper from Chris Russo’s group says yes, and indicates that the answer lies in reducing the electron energy in the cryo-EM from the current standard of 300 or 200 kiloelectron volts (keV) to 100 keV.

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Structural insights into control of cell growth by nutrient availability

mTORC1 recruited to a lysosome by Rag GTPases in order to be activated by RHEB

Structures of active Rag dimers bound to mTORC1 provide greater understanding of control of cell growth and identify potential targets for development of new cancer drugs
Control of cell division is crucially important, as unregulated cell division is a hallmark of cancer. mTORC1 protein kinase is an ancient enzyme complex and master regulator of growth and metabolism that integrates signals relating to nutrient availability, energy, and growth factors.

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How chromosomes are bound to be separated in cell division

Cryo-EM structure of the inner kinetochore-Cenp-A nucleosome complex

The first structure of the inner kinetochore bound to a centromeric nucleosome shows how chromosomes are bound before being segregated into two new cells
When our cells divide, it is important that the pairs of chromosomes are correctly segregated, as errors in this process cause serious problems. For over a century, kinetochores have been recognised as the critical cellular structures responsible for attaching the chromosomes to the microtubules that direct this chromosomal segregation.

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Mapping the human kidney

Scientists use single cell RNA sequencing data to generate the world’s first healthy human kidney cell atlas, providing a critical stepping-stone to understanding the pathways that lead to kidney disease and help identify future therapies
Chronic kidney disease affects more than 500 million patients worldwide, but there are no specific treatments that prevent disease progression.

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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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