Enzymes are proteins that accelerate the conversion of substrate molecules into product molecules. Many enzymes accelerate reactions through formation of chemical bonds to their substrates, but the complexes formed this way are difficult to characterise, as they are intrinsically short-lived.
Researchers in Jason Chin’s group in the LMB’s PNAC Division have for the first time engineered and optimised a ‘stapled’ ribosome that can act as a cell-based factory for synthetic protein polymer synthesis.
We are familiar with polymers in everyday life, from nylon to kevlar and plastics. Polymers are composed of chemical compounds strung together like beads in a necklace.
Circadian rhythms dominate our lives through our daily cycle of sleep and wakefulness. These rhythms are controlled by a master clock in the brain: the suprachiasmatic nucleus (SCN). Studying neuronal cell biology and how the SCN drives behaviour in humans and all animals has been made easier by the development of tools that allow rapid, reversible, and conditional control of these systems.
We each replicate billions of metres of DNA every hour in our dividing cells and it is important that this DNA is replicated accurately. This requires a complex set of machinery called the replisome to unwind the paired strands of DNA allowing different polymerase enzymes to produce new copies. DNA replication is further complicated by the antiparallel structure of DNA: the two strands run in opposite directions alongside one another, and DNA polymerases can only function in one direction.
The human genome encodes thousands of proteins that are embedded in the membranes of all cells. These membrane proteins have numerous functions ranging from ion transport, to cell communication, to sensing odours, and others. In order to carry out these functions, they must be precisely oriented, folded, and assembled correctly.
A collaborative team from the LMB’s Cell Biology and Structural Studies Divisions has identified a cellular factor that detects ribosome collisions. The ribosome is the molecular machine responsible for reading the genetic code to produce proteins, a process known as translation. Such collisions between ribosomes are a sign that something has gone awry during translation, and the collision-detecting factor is critical for initiating pathways to resolve the problem.
As well as having instinctive responses to their environment, nearly all animals can learn to associate particular sights, smells, or sounds with rewards or negative consequences. It had been thought that two separate brain centres control these two different types of responses; innate and learned.
Internal transport between different cellular compartments is a complicated process requiring formation of transport carriers, and sorting the right cargo into those carriers, for delivery to the correct part of the cell. Retromer is a protein complex that forms transport carriers departing from the cell’s central sorting station, the endosome. The architecture of the complex and how it contributes to carrier formation and cargo sorting was unknown.
Cells need to respond quickly when they encounter stress conditions in order to avoid consequences such as cell death. New research from Madan Babu’s group in the LMB’s Structural Studies Division has identified a mechanism by which cells can enhance the expression of stress-response genes by increasing the efficiency of protein synthesis specifically for these genes.
Michel Goedert’s group in the LMB’s Neurobiology Division and Sjors Scheres’ group in the LMB’s Structural Studies Division have used electron cryo-microscopy (cryo-EM) to solve the structures of tau filaments from patients with the frontotemporal dementia Pick’s disease.