Human eggs are frequently aneuploid, meaning they have the wrong number of chromosomes, and this is a major cause of pregnancy loss and Down syndrome. Aneuploidy in human eggs increases with advanced maternal age, which may explain why it is more difficult for women to get pregnant as they get older, and why miscarriages and Down syndrome are more likely in women of advanced age. However, the causes of this maternal age effect in humans have until recently been largely unclear.
DNA damage represents a constant threat to the integrity of genomic information in cells and is closely linked to the origins of cancer. DNA single-strand breaks (SSBs) are the most frequent type of damage with thousands of such lesions from different sources occurring in each cell every day.
Ribosomes, the molecular machines in cells that make proteins, are constructed in a series of discrete steps to create both a large and a small subunit. Release of a key building block, eIF6, from the large 60S subunit allows assembly of the mature active ribosome.
The process of autophagy, in which unnecessary or dysfunctional cellular components are degraded, is important to prevent accumulation of cellular waste and can be triggered by cellular stress.
Formaldehyde, or formalin, is well known to all of us as a common chemical used in many industrial processes and also as a preservative, remarkably we also produce formaldehyde in our bodies. This “endogenous” formaldehyde is ubiquitous, and sufficient amounts might be produced that could damage our cells.
New research by John O’Neill, in the LMB’s Cell Biology Division, and Kenneth Wright, at the University of Colorado, has revealed the mechanism by which caffeine affects the human body clock. The body’s internal clock affects many aspects of human health and disease, such as when we feel sleepy, how we metabolise food, and even when in the day we observe the best athletic and cognitive performance.
The atomic structure of the 170 kDa membrane protein gamma-secretase, a membrane protein complex that has an important role in Alzheimer’s disease, has been solved using single-particle electron cryo-microscopy (cryo-EM) by Sjors Scheres’ group in the LMB’s Structural Studies Division. This demonstrates for the first time that high-resolution reconstruction of such small molecules can be achieved using cryo-EM.
New research from the LMB’s Cell Biology and Structural Studies Divisions has answered a long-standing problem in molecular biology: how does the ribosome decode the signals to stop protein synthesis? In cells, all proteins are produced by ribosomes that ‘read’ messenger RNA (mRNA) one codon, or three nucleotides, at a time. Protein translation terminates when a ribosome reaches one of three nucleotide sequences that encode for stop codons.
In a long-standing collaborative effort, groups at MRC Harwell, the LMB, and the University of Oxford have discovered a new genetic mechanism in the circadian body clock that could have important implications for research in mental health and psychiatric disease. Biological clocks run in all our cells, controlling the timing of a number of crucial daily body functions such as core body temperature, hormone production and brain wave activity.
Early-onset Parkinson’s disease arises when the Parkin protein, an E3 ubiquitin ligase, cannot be activated and remains in a permanently ‘off’ state in neurons. Despite the importance of Parkin activation, until recently no-one has understood how the protein could be switched on. David Komander’s group, in the LMB’s Protein and Nucleic Acid Chemistry Division, has now revealed the structure of Parkin bound to an activator, phospho-ubiquitin.