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.
Genes are encoded in DNA and need to be copied into an intermediate mRNA molecule that contains the instructions to allow synthesis of protein. Almost every mRNA has a repetitive sequence at one end called a poly(A) tail. The length of this tail specifies the amount of time that the mRNA is present in the cell, and how often it is translated into protein. Errors or changes in the tail are found in human diseases including β-thalassemia, thrombophilia and cancer, as well as viral infections.
The connectome of an animal is the comprehensive map, or wiring diagram, of all the neural connections in the brain. However, an important challenge is how to make sense of this information. The nematode worm Caenorhabditis elegans, still the only animal for which the entire connectome has been described, illustrates the problem. Although it has only 302 neurons, these make thousands of connections.
Cell growth requires the synthesis of molecules, such as nucleotides to make DNA and amino acids to make proteins. One essential building block of these is the one carbon unit. This is produced by the one carbon (1C) cycle, which requires the vitamin folate and the amino acid serine (the main source of the 1C unit). 1C metabolism is important for human health, and folate deficiency causes birth defects, nerve damage and anaemia.
Amino acids are the building blocks of proteins. Just twenty different amino acids are strung together in different orders – like beads – to build all the proteins in living organisms. When a single type of amino acid is found consecutively within a protein, this is known as a homorepeat. Abnormal variation in the length of amino acid homorepeats has long been known to be associated with disease, such as Huntington’s.
The cells in our body contain numerous molecular machines that carry out nearly all biological processes essential for life. These machines are built from proteins that are often assembled into complex structures. For example ribosomes contain 80 distinct proteins on a scaffold of four different RNAs. The assembly of such structures from so many parts is a complicated process and inevitably results in ‘leftover’ proteins.
Proteins can be reversibly phosphorylated – phosphate groups are added to proteins by the action of kinase enzymes and can be removed by phosphatases. This controls a huge variety of cellular processes and targeting phosphorylation thus offers a board range of therapeutic opportunities. Indeed, kinases have received much attention in pharmaceutical research, yet phosphatases have been largely untapped.