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.
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.
When cells divide, they must accurately copy their genetic material (DNA) and also ensure that their pattern of gene expression is maintained – genes that were ‘on’ before the cell divides need to remain on in the daughter cell, and genes that were ‘off’ need to remain off. These patterns of gene expression are determined by epigenetic signals, and it is possible to alter these signals to reprogram gene expression.
Neural networks, circuits of neurons, are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that neural network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. Yet our ability to target and study specific neural networks remains limited. Until now Rabies virus, which can jump synapses, has been used to investigate neural networks.