Insight on Research


New hypothesis for the formation of macropinocytic cups

Dictyostelium cell making four macropinosomes, each of which is organised around a patch of PIP3 (orange) with SCAR/WAVE recruited to its perimeter (green)

Macropinocytosis, the cellular uptake of fluids from the environment, is employed by a variety of cells and requires the formation of a cup-shaped structure that protrudes from the cell’s surface and captures gulps of medium. Polymerisation of actin under the plasma membrane drives the extension of macropinocytic cups. However, until now it has been unclear how the actin forming the walls of the cup is shaped into a ring.

More…

Published

Recovering stalled ribosomes

ArfA and RF2 bound to the bacterial ribosome

Ribosomes are cellular molecular machines that link amino acids together in the order specified by messenger RNA (mRNA) to make proteins. Near the end of the mRNA molecule a specific nucleotide sequence, known as a stop codon, signals for protein synthesis to terminate by recruiting release factors that release the newly made protein from the ribosome and recycle the ribosome to start another round of protein synthesis.
However, some mRNA molecules are defective.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published

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.

More…

Published