Effective immunity to infections requires the development of a diverse repertoire of antibodies. Antibody diversity is created through a process known as somatic hypermutation, which is the programmed mutation of specific sequences of DNA in the antibody genes. The introduction of mutations results in the production of antibodies that recognise and bind to different antigens, such as microbes, and allows the immune system to adapt as it is exposed to new antigens.
Target of Rapamycin (TOR) is a protein kinase that is essential in maintaining cellular homeostasis. In mammalian cells the enzyme occurs as two large protein complexes and one of these, mTORC1, controls growth of cells by integrating signals from growth factors and the nutritional state of cells. Many tumours in humans are associated with inappropriate regulation of this protein complex, and it has been demonstrated to be an important therapeutic target for cancer and autoimmune disorders.
Most organisms, including humans and plants, have circadian rhythms that allow them to adjust their metabolism and behaviour to match the 24-hour cycle of day and night. Circadian rhythms are even observed at the level of individual cells, and are dependent upon a biological clock mechanism that is not fully understood.
‘Synthetic biology’ is a scientific approach that seeks to answer fundamental questions in biology by reconstruction and modification of the molecules and processes of life. Beyond its well-known role as the carrier of genetic information, DNA (and its close cousin RNA) have shown great promise as a nano-molecular building material: by careful arrangement of the bases A, T, C and G, DNA strands can be programmed to fold into specific 3D shapes.
Information transfer in the nervous system occurs at synapses, where presynaptic signals are interpreted by postsynaptic receptors. Ingo Greger’s group, in the LMB’s Neurobiology Division, study this process with a focus on AMPA-type glutamate receptors (AMPARs) at various levels of complexity. AMPARs are the prime mediators of excitatory neurotransmission and are regulators of synaptic plasticity, which underlies learning.
Every year hundreds of millions of people worldwide are affected by Malaria and nearly half a million die from the disease. More than two thirds of those dying are children under five. The disease is caused by parasites passed to humans through the bites of infected mosquitoes, with Plasmodium falciparum being the parasite responsible for the most severe form of malaria.
Cell-to-cell variability in gene expression level (noise) has emerged as one of the fundamental concepts in genetics. Non-genetic, cell-to-cell variation in the abundance of a gene product can generate a diversity of behaviour in genetically identical population of cells. This phenomenon is pervasive and prevalent in development (e.g. stem cells) and disease (e.g. cancer). Genome-scale studies on gene expression noise have revealed that some genes are more random in their expression than others.
Researchers in the LMB’s Structural Studies Division have been able to show in more detail than ever before the structure of a large part of the spliceosome, a macromolecular machine involved in the maturation of messenger RNAs for protein synthesis.
Rebecca Voorhees and Manu Hegde, from the LMB’s Cell Biology Division, have used cryo-electron microscopy (cryo-EM) to determine how a channel that is essential for protein transport is opened. This channel, known as Sec61 in mammals, is needed for secretion of proteins from the cell and insertion of proteins into the membrane.
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.