MRC Laboratory of Molecular Biology
One of the world's leading research institutes, our scientists are working to advance understanding of biological processes at the molecular level - providing the knowledge needed to solve key problems in human health.
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.
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.
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.
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.
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.
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.