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.
When an animal detects a stimulus that might signal danger, this primes sensory and motor organs to respond more readily to further stimulation. This is called sensitisation and is one aspect of the more general phenomenon of arousal, in which animals become more alert and can respond more effectively to potential threats. However, the basic principles of how arousal is triggered have not been fully understood.
Many complex tubular organs, including kidney, lung, the intestine and several glands, form from a flat layer of cells during animal development. Failure of proper tube formation underlies severe congenital malformations such as Spina Bifida, and the failure to maintain tube architecture for instance underlies Polycystic Kidney Diseases. How tissues transition from flat 2D structures to 3D tubes is poorly understood.
Scientists have identified planets outside our solar system where the same chemical conditions exist that may have led to life on Earth. The researchers, from John Sutherland’s group in the LMB’s PNAC Division and the University of Cambridge Cavendish Laboratory, found that the chances for life to develop on the surface of a rocky planet like Earth are connected to the type and strength of light given off by its host star.
Anne Bertolotti’s group in the LMB’s Neurobiology Division have developed the first platform to discover selective inhibitors of phosphatases, a class of enzyme which have largely been considered ‘undruggable’. This has allowed Anne’s group to identify a small molecule, Raphin1, which selectively inhibits a protein phosphatase and is effective in a mouse model of Huntington’s disease – an exciting step in the potential treatment of neurodegenerative diseases.