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.

Determination of nucleotide sequences in DNA

Abstract: In spite of the important role played by DNA sequences in living matter, it is only relatively recently that general methods for their determination have been developed. This is mainly because of the very large size of DNA molecules, the smallest being those of the simple bacteriophages such as qXl74 (which contains about 5,000 nucleotides). It was therefore difficult to develop methods with such complicated systems. There are however some relatively small RNA molecules notably the transfer RNAs of about 75 nucleotides, and these were used for the early studies on nucleic acid sequences (1). Following my work on amino acid sequences in proteins (2) I turned my attention to RNA and, with G.G. Brownlee and B.G. Barrell, developed a relatively rapid small-scale method for the fractionation of P-labelled oligonucleotides (3). This became the basis for most subsequent studies of RNA sequences. The general approach used in these studies, and in those on proteins, depended on the principle of partial degradation. The large molecules were broken down, usually by suitable enzymes, to give smaller products which were then separated from each other and their sequence determined. When sufficient results had been obtained they were fitted together by a process of deduction to give the complete sequence. This approach was necessarily rather slow and tedious, often involving successive digestions and fractionations, and it was not easy to apply it to the larger DNA molecules. When we first studied DNA some significant sequences of about 50 nucleotides in length were obtained with this method (4,5), but it seemed that to be able to sequence genetic material a new approach was desirable and we turned our attention to the use of copying procedures.

Guided self-organization and cortical plate formation in human brain organoids

Abstract: Three-dimensional cell culture models have either relied on the self-organizing properties of mammalian cells or used bioengineered constructs to arrange cells in an organ-like configuration. While self-organizing organoids excel at recapitulating early developmental events, bioengineered constructs reproducibly generate desired tissue architectures. Here, we combine these two approaches to reproducibly generate human forebrain tissue while maintaining its self-organizing capacity. We use poly(lactide-co-glycolide) copolymer (PLGA) fiber microfilaments as a floating scaffold to generate elongated embryoid bodies. Microfilament-engineered cerebral organoids (enCORs) display enhanced neuroectoderm formation and improved cortical development. Furthermore, reconstitution of the basement membrane leads to characteristic cortical tissue architecture, including formation of a polarized cortical plate and radial units. Thus, enCORs model the distinctive radial organization of the cerebral cortex and allow for the study of neuronal migration. Our data demonstrate that combining 3D cell culture with bioengineering can increase reproducibility and improve tissue architecture.

Tubulin and FtsZ form a distinct family of GTPases.

Abstract: Tubulin and FtsZ share a common fold of two domains connected by a central helix. Structure-based sequence alignment shows that common residues localize in the nucleotide-binding site and a region that interacts with the nucleotide of the next tubulin subunit in the protofilament, suggesting that tubulin and FtsZ use similar contacts to form filaments. Surfaces that would make lateral interactions between protofilaments or interact with motor proteins are, however, different. The highly conserved nucleotide-binding sites of tubulin and FtsZ clearly differ from those of EF-Tu and other GTPases, while resembling the nucleotide site of glyceraldehyde-3-phosphate dehydrogenase. Thus, tubulin and FtsZ form a distinct family of GTP-hydrolyzing proteins.