Laboratory of Molecular Biology

About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.

Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

Abstract: Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

Clock-like mutational processes in human somatic cells

Abstract: During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operating in human somatic cells.

Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases.

Abstract: HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-1 integrase was determined at 2.5 A resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with a extensive solvent-inaccessible interface of 1300 A2 per monomer.

Membrane Structure: Some General Principles

Abstract: The arrangement of lipids and some proteins in the erythrocyte membrane has been discussed. The conclusions from this are listed here as a set of general guidelines for the structure of membranes of higher organisms: some of these rules may be wrong. But at this stage it seems useful to sharpen our thoughts in this way and thereby focus attention on various specific points. 1) The basis of a membrane is a lipid bilayer with (i) choline phospholipids and glycolipids in the external half and (ii) amino (and possibly some choline) phospholipids in the cytoplasmic half. There is effectively no lipid exchange across the bilayer (unless enzymatically catalyzed) (68). 2) Some proteins extend across the bilayer. Where this is so, they will in general have carbohydrate on their surface remote from the cytoplasm. This carbohydrate may prevent the protein diffusing out of the membrane into the cytoplasm; it acts as a lock on the protein. 3) Just as lipids do not flip-flop, proteins do not rotate across the membrane. Lateral motion or rotation of lipids and proteins in the plane of the bilayer may be expected. 4) Most membrane protein is associated with the inner, cytoplasmic, urface of the membrane. Proteins are not usually associated exclusively with the outer half of the lipid bilayer. 5) Membrane proteins are a special class of cytoplasmic proteins, not of secreted proteins.