Insight on Research


Cryo-electron microscopy reveals near-atomic resolution structure of the prespliceosome

Two alternative splicing factors

Kiyoshi Nagai’s group in the LMB’s Structural Studies Division have used electron cryo-microscopy to solve the structure of the prespliceosome at near-atomic resolution, providing new insights into how the spliceosome is assembled and regulated.
The human genome contains approximately 20,000 genes, which when transcribed produce precursor messenger RNA (pre-mRNA) consisting of coding sequences (exons) and non-coding sequences (introns).

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Discovering how translation and mRNA decay are linked

Gel showing global poly(A) tail lengths which shorten over time

Scientists in Lori Passmore’s group in the LMB’s Structural Studies Division have revealed new mechanistic insights into the link between translation and mRNA decay.

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Uncovering the structure of the serotonin receptor

G protein-coupled receptor

Scientists in Chris Tate’s group in the LMB’s Structural Studies Division have used cryo-electron microscopy to determine the structure of the serotonin receptor coupled to the heterotrimeric G protein Go, providing insights into how receptors bind specific G proteins.
Communication between cells throughout our bodies is vital for our health. Cells release signals, such as hormones and neurotransmitters, which must then be received and communicated to the inside of the recipient cell.

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Controlling actin polymerisation in clathrin mediated endocytosis

Clathrin mediated endocytosis

Work from Harvey McMahon’s group in the LMB’s Neurobiology Division has uncovered how a protein, FCHSD2, controls actin polymerisation during endocytosis. Importantly the scientists discovered that FCHSD2 does its job from the area surrounding the site of endocytosis – making it the first description of an endocytic protein which localises to the flat region around endocytic events.

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Parkin activation and early-onset Parkinson’s disease: the last piece of the puzzle

The structure of activated phospho-Parkin bound to phospho-ubiquitin

Researchers at the LMB have solved the elusive 3D structure of activated Parkin, an enzyme implicated in early-onset Parkinson’s disease. Led by David Komander’s group in the LMB’s PNAC Division, in collaboration with the LMB’s Biological Mass Spectrometry facility, this new work reveals insights into previously unstudied parts of this important protein and helps explain why families with certain mutations in Parkin suffer from early-onset Parkinson’s disease.

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How does the replisome respond to DNA damage?

Diagram to illustrate replication of damaged DNA in a test tube

Work by Joe Yeeles’ group in the LMB’s PNAC Division has for the first time revealed the earliest responses when the eukaryotic DNA replication machinery, the replisome, collides with DNA damage.
Every time a cell divides, its DNA must be replicated so that each daughter cell inherits a complete copy of the genome.

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HIV exploits a native cellular molecule to increase the stability of its capsid

IP6 anchors the HIV capsid

Scientists in Leo James’ group in the LMB’s PNAC Division, in collaboration with Till Böcking’s group at the University of New South Wales, Australia and Adolfo Saiardi’s group at the MRC Laboratory for Molecular Cell Biology, have uncovered how the HIV virus stabilises its capsid by binding to an abundant cellular polyanion, IP6.

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Three-dimensional representation of motor space in the brain

In our day-to-day lives we execute spatially targeted movements with ease and seemingly without much thought. These movements may include reaching for your morning cup of coffee, checking your mirrors on your drive into work, or catching a cricket ball.

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How the earliest life on Earth may have replicated itself

Liquid brine containing replicating RNA molecules is concentrated in the cracks between ice crystals, as seen with an electron microscope

Scientists in Philipp Holliger’s group in the LMB’s PNAC Division have created a new type of genetic replication system to demonstrate how the first life on Earth – in the form of RNA – could have replicated itself.
Our understanding of life’s early history is limited but a popular theory for the earliest stages of life on Earth is that it was founded on strands of RNA, a chemical cousin of DNA.

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Next generation sequencing and machine learning provide insights into the dark proteome

: IDR-Screen helps to identify functional segments in disordered protein regions (dark proteome)

Work from Madan Babu’s group in the LMB’s Structural Studies Division, spearheaded by Charles Ravarani and in collaboration with Alexandre Erkine’s group at Butler University, has for the first time harnessed next generation sequencing and machine learning to develop a high throughput screen to uncover disordered regions of proteins that are functional within cells.
Proteins, the molecular machines of the cell, are formed from chains of amino acids.

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