Insight on Research


New technologies enable systematic recoding of genomes

GENESIS via REXER schematic

The design and synthesis of genomes provides a powerful approach for understanding and engineering biology. The development of methods that can accurately replace the genome in sections, provide feedback on precisely where a given design fails and on how to repair it, and that can be rapidly repeated for whole genome replacement would accelerate our ability to understand and manipulate the information encoded in genomes. Using E.

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New insights into the mechanism of ubiquitin chain cleavage

Cezanne–Lys11 diubiquitin complex structure

The ubiquitin system is a complex system in all eukaryotic organisms involved in the regulation of most cellular processes. A huge variety of signals are assembled with ubiquitin molecules onto cellular proteins to mark them for a specific task. Important regulators of the ubiquitin system are deubiquitinating enzymes (DUBs), which remove, or cleave, ubiquitin chains in order to reverse these modifications.

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Molecular mechanism triggering assembly of the Wnt signalosome uncovered

Model of Wnt signalosome assembly by domain swapping of Dishevelled (DVL)

The Wnt signaling pathway is an ancient cell communication pathway that has important roles in development and cancer. For the first time, work by Mariann Bienz’s group in the LMB’s PNAC Division has uncovered the molecular mechanism triggering the assembly of the Wnt signalosome, a key component of the Wnt signal transduction pathway that controls normal development and tissue homeostasis in all animals.

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Augmenting CRISPR genome editing applications

Use of tRNA-gRNA arrays to disrupt production of a protein in a specific tissue

The ability of scientists to create changes in gene sequences has improved dramatically in recent years with the emergence of a new method, dubbed ‘CRISPR’. This ‘genome editing’ technology is of great interest due to the wide range of possible applications. CRISPR is already commonly used in fundamental research to study the function of specific genes in either cultured cells or whole animal models of human biology.

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Molecular principles of gene fusion mediated protein interaction networks in cancer

Diagram network rewiring cancer gene fusions

Gene fusions, which occur when two previously separate genes become aberrantly fused together, are common cancer-causing mutations. What remain unknown are the molecular functions of most gene fusions, and the proteins that gene fusions can encode (fusion proteins). This lack of functional understanding is a growing problem, since the number of detected gene fusions in cancer continues to rise with advances in modern sequencing technologies.

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Major breakthrough identifies cause and treatment of fatal autoimmune disease

Graphical depiction of symptoms of ORAS (OTULIN-related Autoinflammatory Syndrome)

The cause of a potentially fatal inherited autoimmune disease has been identified for the first time. The disease, now named OTULIN-related autoinflammatory syndrome (ORAS), was discovered by doctors treating patients who developed symptoms such as rashes, fever, and diarrhoea shortly after birth. The immune system of these patients spontaneously activates and starts to attack the patient’s own body leading to the described symptoms and eventually to the child’s death.

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Molecular basis of APC/C regulation by the spindle assembly checkpoint

During eukaryotic cell division (mitosis) the cell’s chromosomes are duplicated and then equally separated into two new daughter cells. To prevent errors in mitosis cells employ checkpoints that monitor and coordinate the correct order of events. Checkpoints either delay cell division, or if unrecoverable, cause cell death.

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HIV uses capsid pores to import nucleotides and evade innate immunity

HIV is a retrovirus, meaning it has to copy its RNA genome into DNA in order to infect cells. While much has been learned about the virus, investigators don’t understand how it evades our immune system so successfully. A long-standing question has been how the HIV virus copies its genome using raw materials from the cell without being detected by immune sensors.

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An evolutionarily conserved pathway controls proteasome homeostasis

Cell survival depends on adaptive signalling pathways to ensure that the supply of vital components matches the fluctuating needs of the cell. The proteasome is essential for the selective degradation of most cellular proteins and thereby controls virtually all cellular processes. The current prevailing view is that protein degradation is largely regulated at the level of ubiquitination.

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Structure of the catalytic spliceosome

model of spliceosome structure

The spliceosome is a molecular machine, which together with RNA polymerases and ribosomes plays a critical role in basic gene expression. Due to its highly dynamic nature the structure of the spliceosome has remained elusive until now. Research by Kiyoshi Nagai’s group, in the LMB’s Structural Studies Division, has for the first time captured the spliceosome in a fully active, substrate-bound state, immediately after first catalytic reaction.

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