Simulation of packet and cell-based communication networks

This thesis investigates, using simulation techniques, the practical aspects of implementing a novel mobility protocol on the emerging Broadband Integrated Services Digital Network standard. The increasing expansion of telecommunications networks has meant that the demand for simulation has increased rapidly in recent years; but conventional simulators are slow and developments in the communications field are outstripping the ability of sequential uni-processor simulators. Newer techniques using distributed simulation on a multi-processor network are investigated in an attempt to make a cell-level simulation of a non-trivial B.-I.S.D.N. network feasible. The current state of development of the Asynchronous Transfer Mode standard, which will be used to implement a B.-I.S.D.N., is reviewed and simulation studies of the Orwell Slotted Ring protocol were made in an attempt to devise a simpler model for use in the main simulator. The mobility protocol, which uses a footprinting technique to simplify hand- offs by distributing information about a connexion to surrounding base stations, was implemented on the simulator and found to be functional after a few 'special case' scenarios had been catered for

DNA packaging by molecular motors: from bacteriophage to human chromosomes

Dense packaging of genomic DNA is crucial for organismal survival, as DNA length always far exceeds the dimensions of the cells that contain it. Organisms, therefore, use sophisticated machineries to package their genomes. These systems range across kingdoms from a single ultra-powerful rotary motor that spools the DNA into a bacteriophage head, to hundreds of thousands of relatively weak molecular motors that coordinate the compaction of mitotic chromosomes in eukaryotic cells. Recent technological advances, such as DNA proximity-based sequencing approaches, polymer modelling and in vitro reconstitution of DNA loop extrusion, have shed light on the biological mechanisms driving DNA organization in different systems. Here, we discuss DNA packaging in bacteriophage, bacteria and eukaryotic cells, which, despite their extreme variation in size, structure and genomic content, all rely on the action of molecular motors to package their genomes

A perfect funeral with no corpse

“Indeed, the role in mitosis of the chromosome arms, which carry most of the genetic material, may be compared with that of a corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961

William R. Brinkley:A giant in biomedical research and public policy

Susan A. Gerbi, Robert E. Palazzo, William C. Earnshaw, and William T. Schrader discuss the life and achievements of William R. Brinkley, who passed away on November 10, 2020

Essential Roles of Drosophila Inner Centromere Protein (Incenp) and Aurora B in Histone H3 Phosphorylation, Metaphase Chromosome Alignment, Kinetochore Disjunction, and Chromosome Segregation

We have performed a biochemical and double-stranded RNA-mediated interference (RNAi) analysis of the role of two chromosomal passenger proteins, inner centromere protein (INCENP) and aurora B kinase, in cultured cells of Drosophila melanogaster. INCENP and aurora B function is tightly interlinked. The two proteins bind to each other in vitro, and DmINCENP is required for DmAurora B to localize properly in mitosis and function as a histone H3 kinase. DmAurora B is required for DmINCENP accumulation at centromeres and transfer to the spindle at anaphase. RNAi for either protein dramatically inhibited the ability of cells to achieve a normal metaphase chromosome alignment. Cells were not blocked in mitosis, however, and entered an aberrant anaphase characterized by defects in sister kinetochore disjunction and the presence of large amounts of amorphous lagging chromatin. Anaphase A chromosome movement appeared to be normal, however cytokinesis often failed. DmINCENP and DmAurora B are not required for the correct localization of the kinesin-like protein Pavarotti (ZEN-4/CHO1/MKLP1) to the midbody at telophase. These experiments reveal that INCENP is required for aurora B kinase function and confirm that the chromosomal passengers have essential roles in mitosis

The intrinsically disorderly story of Ki-67

Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid–liquid phase separation of nucleolar proteins and RNAs

Mapping the invisible chromatin transactions of prophase chromosome remodeling

We have used a combination of chemical genetics, chromatin proteomics, and imaging to map the earliest chromatin transactions during vertebrate cell entry into mitosis. Chicken DT40 CDK1(as) cells undergo synchronous mitotic entry within 15 min following release from a 1NM-PP1-induced arrest in late G(2). In addition to changes in chromatin association with nuclear pores and the nuclear envelope, earliest prophase is dominated by changes in the association of ribonucleoproteins with chromatin, particularly in the nucleolus, where pre-rRNA processing factors leave chromatin significantly before RNA polymerase I. Nuclear envelope barrier function is lost early in prophase, and cytoplasmic proteins begin to accumulate on the chromatin. As a result, outer kinetochore assembly appears complete by nuclear envelope breakdown (NEBD). Most interphase chromatin proteins remain associated with chromatin until NEBD, after which their levels drop sharply. An interactive proteomic map of chromatin transactions during mitotic entry is available as a resource at https://mitoChEP.bio.ed.ac.uk