Insight on Research


New understanding of protein abundance control

Translating ribosomes with the emerging protein acting as a beacon

Cells tightly control the levels of ‘housekeeping’ proteins to maintain smooth operation of basic life processes. The most common way cells accomplish this task is feedback control of transcription to turn on or turn off genes in response to perceived need of their protein products.

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Decade-long collaboration results in the first structure of the Fanconi anaemia core complex

Fanconi anaemia core complex structure

Our DNA contains all of the information required to tell a cell what it needs to do, but it is constantly being damaged. This damage can cause severe problems, making repair processes hugely important. One common type of DNA damage, known as crosslinking, involves links forming inappropriately between two nucleotide letters. Although the specific repair pathway that fixes DNA crosslinks, and the complex at the heart of it, have been known about for decades, a full mechanistic understanding has been missing. Lori Passmore’s group, in the LMB’s Structural Studies Division, has now revealed the structure of the complex at the heart of this repair pathway for the first time.

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

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

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. Recent measurements of radiation damage to biological specimens by high-energy electrons have shown that at lower energies there is an increased amount of information available per unit damage. The authors of the paper foresee that future cryo-microscopes designed for ultimate single-particle resolution will be designed to maximise this information. This will then make true atomic resolution (~1 Å) more accessible and affordable.

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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

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. Activation of mTORC1 is driven by proteins called Rags that sense nutrient abundance. However, some cancer-causing mutations make Rag proteins active even in the absence of nutrients and drive cells to divide when they shouldn’t. Roger Williams’ group, in the LMB’s PNAC Division, has now shown how active Rags bind to mTORC1 and how a cancer-associated mutation can make a Rag protein continuously active.

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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

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. However, how exactly kinetochores recognise the centromere, the central point that links the two halves of a chromosome, has been a long-standing question. David Barford’s group in the LMB’s Structural Studies Division and Stephen McLaughlin of the LMB’s Biophysics Facility, have now determined a structure of a kinetochore complex that suggests the answer to this question.

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Mapping the human kidney

Chronic kidney disease affects more than 500 million patients worldwide, but there are no specific treatments that prevent disease progression. A lack of tissue availability has limited research into human kidney function and animal research hasn’t translated into treatments for human patients. Menna Clatworthy’s group, in the University of Cambridge Molecular Immunity Unit, which is housed within the LMB, has now generated the first atlas-scale dataset map of human kidney cells, which will begin to address this knowledge gap.

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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,

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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,

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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.

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