Nigel Burroughs | University of Warwick (original) (raw)

Papers by Nigel Burroughs

In this paper we examine the bi-Hamiltonian structure of the generalized KdV-hierarchies. We veri... more In this paper we examine the bi-Hamiltonian structure of the generalized KdV-hierarchies. We verify that both Hamiltonian structures take the form of Kirillov brackets on the Kac-Moody algebra, and that they define a coordinated system. Classical extended conformal algebras are obtained from the second Poisson bracket. In particular, we construct the WnlW_n^lWnl algebras, first discussed for the case n=3n=3n=3 and

Journal of cell science, Jan 23, 2015

Kinetochores regulate the dynamics of attached microtubule bundles (K-fibres) to generate the for... more Kinetochores regulate the dynamics of attached microtubule bundles (K-fibres) to generate the forces necessary for chromosome movements in mitosis. Current models suggest that poleward (P) moving kinetochores are attached to depolymerising K-fibres and anti-poleward (AP) moving kinetochores to polymerising. How the dynamics of individual microtubules within the kinetochore-fibre (K-fibre) relate to P and AP movements is poorly understood. To investigate this, we developed a live-cell imaging assay combined with computational image analysis that allows EB3-eGFP to be quantified at thousands of individual metaphase kinetochores as they undergo P and AP motion. Surprisingly, we found that K-fibres are incoherent, containing both polymerising and depolymerising microtubules - with a small polymerisation bias for AP moving kinetochores. K-fibres also display bursts of EB3 intensity, predominantly on AP moving kinetochores, equivalent to more coherent polymerisation and were associated wi...

PLoS ONE, 2011

Background: In cyanobacteria the photosystems are localised to, and maintained in, specialist mem... more Background: In cyanobacteria the photosystems are localised to, and maintained in, specialist membranes called the thylakoids. The mechanism driving the biogenesis of the thylakoid membranes is still an open question, with only two potential biogenesis factors, Vipp1 and Alb3 currently identified.

Viral recombination is a key evolutionary mechanism, aiding escape from host immunity, contributi... more Viral recombination is a key evolutionary mechanism, aiding escape from host immunity, contributing to changes in tropism and possibly assisting transmission across species barriers. The ability to determine whether recombination has occurred and to locate associated specific recombination junctions is thus of major importance in understanding emerging diseases and pathogenesis. This paper describes a method for determining recombinant mosaics (and their proportions) originating from two parent genomes, using high-throughput sequence data. The method involves setting the problem geometrically and the use of appropriately constrained quadratic programming. Recombinants of the honeybee deformed wing virus and the Varroa destructor virus-1 are inferred to illustrate the method from both siRNAs and reads sampling the viral genome population (cDNA library); our results are confirmed experimentally. Matlab software (MosaicSolver) is available.

Bioinformatics (Oxford, England), 2014

There are a number of algorithms to infer causal regulatory networks from time series (gene expre... more There are a number of algorithms to infer causal regulatory networks from time series (gene expression) data. Here we analyse the phenomena of regulator interference, where regulators with similar dynamics mutually suppress both the probability of regulating a target and the associated link strength; for instance, interference between two identical strong regulators reduces link probabilities by ∼50%. We construct a robust method to define an interference-corrected causal network based on an analysis of the conditional link probabilities that recovers links lost through interference. On a large real network (Streptomyces coelicolor, phosphate depletion), we demonstrate that significant interference can occur between regulators with a correlation as low as 0.865, losing an estimated 34% of links by interference. However, levels of interference cannot be predicted from the correlation between regulators alone and are data specific. Validating against known networks, we show that high ...

PLoS Pathogens, 2014

The globally distributed ectoparasite Varroa destructor is a vector for viral pathogens of the We... more The globally distributed ectoparasite Varroa destructor is a vector for viral pathogens of the Western honeybee (Apis mellifera), in particular the Iflavirus Deformed Wing Virus (DWV). In the absence of Varroa low levels DWV occur, generally causing asymptomatic infections. Conversely, Varroa-infested colonies show markedly elevated virus levels, increased overwintering colony losses, with impairment of pupal development and symptomatic workers. To determine whether changes in the virus population were due Varroa amplifying and introducing virulent virus strains and/or suppressing the host immune responses, we exposed Varroa-naïve larvae to oral and Varroa-transmitted DWV. We monitored virus levels and diversity in developing pupae and associated Varroa, the resulting RNAi response and transcriptome changes in the host. Exposed pupae were stratified by Varroa association (presence/absence) and virus levels (low/high) into three groups. Varroa-free pupae all exhibited low levels of a highly diverse DWV population, with those exposed per os (group NV) exhibiting changes in the population composition. Varroa-associated pupae exhibited either low levels of a diverse DWV population (group VL) or high levels of a near-clonal virulent variant of DWV (group VH). These groups and unexposed controls (C) could be also discriminated by principal component analysis of the transcriptome changes observed, which included several genes involved in development and the immune response. All Varroa tested contained a diverse replicating DWV population implying the virulent variant present in group VH, and predominating in RNA-seq analysis of temporally and geographically separate Varroa-infested colonies, was selected upon transmission from Varroa, a conclusion supported by direct injection of pupae in vitro with mixed virus populations. Identification of a virulent variant of DWV, the role of Varroa in its transmission and the resulting host transcriptome changes furthers our understanding of this important viral pathogen of honeybees.

PeerJ, 2014

The impetus for this work was the need to analyse nucleotide diversity in a viral mix taken from ... more The impetus for this work was the need to analyse nucleotide diversity in a viral mix taken from honeybees. The paper has two findings. First, a method for correction of next generation sequencing error in the distribution of nucleotides at a site is developed. Second, a package of methods for assessment of nucleotide diversity is assembled. The error correction method is statistically based and works at the level of the nucleotide distribution rather than the level of individual nucleotides. The method relies on an error model and a sample of known viral genotypes that is used for model calibration. A compendium of existing and new diversity analysis tools is also presented, allowing hypotheses about diversity and mean diversity to be tested and associated confidence intervals to be calculated. The methods are illustrated using honeybee viral samples. Software in both Excel and Matlab and a guide are available at http://www2.warwick.ac.uk/fac/sci/systemsbiology/research/software/, ...

PLoS ONE, 2008

Background: S-PM2 is a phage capable of infecting strains of unicellular cyanobacteria belonging ... more Background: S-PM2 is a phage capable of infecting strains of unicellular cyanobacteria belonging to the genus Synechococcus. S-PM2, like other myoviruses infecting marine cyanobacteria, encodes a number of bacterial-like genes. Amongst these genes is one encoding a MazG homologue that is hypothesized to be involved in the adaption of the infected host for production of progeny phage.

Micron, 2011

Interaction between bacteria and protozoa is an increasing area of interest, however there are a ... more Interaction between bacteria and protozoa is an increasing area of interest, however there are a few systems that allow extensive observation of the interactions. A semi-automated approach is proposed to analyse a large amount of experimental data and avoid a time demanding manual object classification. We examined a surface system consisting of non nutrient agar with a uniform bacterial lawn that extended over the agar surface, and a spatially localised central population of amoebae. Location and identification of protozoa and quantification of bacteria population are performed by the employment of image analysis techniques in a series of spatial images. The quantitative tools are based on intensity thresholding, or on probabilistic models. To accelerate organism identification, correct classification errors and attain quantitative details of all objects a custom written Graphical User Interfaces has also been developed.

Microbial Biotechnology, 2009

Secondary structures and the short Shine-Dalgarno sequence in the 5Ј-untranslated region of bacte... more Secondary structures and the short Shine-Dalgarno sequence in the 5Ј-untranslated region of bacterial mRNAs (UTR) are known to affect gene expression at the level of translation. Here we report the use of random combinatorial DNA sequence libraries to study UTR function, applying the strong, s 32 /s 38dependent, and positively regulated Pm promoter as a model. All mutations in the libraries are located at least 8 bp downstream of the transcriptional start site. The libraries were screened using the ampicillinresistance gene (bla) as reporter, allowing easy identification of UTR mutants that display high levels of expression (up to 20-fold increase relative to the wildtype at the protein level). Studies of the two UTR mutants identified by a modified screening procedure showed that their expression is stimulated to a similar extent at both the transcript and protein product levels. For one such mutant a model analysis of the transcription kinetics showed significant evidence of a difference in the transcription rate (about 18-fold higher than the wild type), while there was no evidence of a difference in transcript stability. The two UTR sequences also stimulated expression from a constitutive s 70 -dependent promoter (P1/Panti-tet), demonstrating that the UTR at the DNA or RNA level has a hitherto unrecognized role in transcription.

Interactions between bacteria and protozoa is an increasing area of interest, however there are a... more Interactions between bacteria and protozoa is an increasing area of interest, however there are a few systems that allow extensive observation of the interactions. We examined a surface system consisting of non nutrient agar with a uniform bacterial lawn that extended over the agar surface, and a spatially localised central population of amoebae. The amoeba fed on bacteria and migrated over the plate. Automated image analysis techniques were used to locate and count amoebae, cysts and bacteria coverage in a series of spatial images. Most algorithms were based on intensity thresholding, or a modification of this idea with probabilistic models. Our strategy was two tiered, we performed an automated analysis for object classification and bacteria counting followed by user intervention/reclassification using custom written Graphical User Interfaces.

Journal of Hepatology, 1999

Orthotopic liver transplantation has an established role for the treatment of patients with chron... more Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. Methods: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. Results: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five IVER TRANSPLANTATION (LT) remains the only treat-L ment option for patients with end-stage liver disease complicating hepatitis B virus (HBV) infection. Unfortunately, graft re-infection with HBV is associated with significant morbidity, and with diminished graft and patient survival. Graft re-infection may be prevented by the administration of HBV hyperimmune . patients developed graft re-infection with lamivudineresistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus.

International Immunology - INT IMMUNOL, 2001

T lymphocyte activation by specific antigen requires prolonged TCR occupancy and sustained signal... more T lymphocyte activation by specific antigen requires prolonged TCR occupancy and sustained signaling. This is accomplished by the formation of a specialized signaling domain, the immunological synapse, at the T cell-antigen-presenting cell contact site. Surface receptors and signaling components are progressively recruited into this domain where they are organized in defined three-dimensional structures. To better understand how TCR are supplied to the signaling domain during the activation process, we measured (using confocal microscopy and photo- bleaching recovery techniques) lateral mobility of GFP-tagged TCR on living Jurkat cell surface. We show that: (i) surface-expressed TCR exhibit an intrinsic, actin cytoskeleton-independent, lateral mobility which allows them to passively diffuse over the entire T cell surface within ~60 min and (ii) non-stimulated TCR rapidly enter the signaling domain. Our results indicate that TCR lateral mobility per se is sufficient to ensure TCR sup...

Immunogenetics, 2004

We studied whether the peptides of nine amino acids (9-mers) that are typically used in MHC class... more We studied whether the peptides of nine amino acids (9-mers) that are typically used in MHC class I presentation are sufficiently unique for self:nonself discrimination. The human proteome contains 28,783 proteins, comprising 10(7) distinct 9-mers. Enumerating distinct 9-mers for a variety of microorganisms we found that the average overlap, i.e., the probability that a foreign peptide also occurs in the human self, is about 0.2%. This self:nonself overlap increased when shorter peptides were used, e.g., was 30% for 6-mers and 3% for 7-mers. Predicting all 9-mers that are expected to be cleaved by the immunoproteasome and to be translocated by TAP, we find that about 25% of the self and the nonself 9-mers are processed successfully. For the HLA-A*0201 and HLA-A*0204 alleles, we predicted which of the processed 9-mers from each proteome are expected to be presented on the MHC. Both alleles prefer to present processed 9-mers to nonprocessed 9-mers, and both have small preference to present foreign peptides. Because a number of amino acids from each 9-mer bind the MHC, and are therefore not exposed to the TCR, antigen presentation seems to involve a significant loss of information. Our results show that this is not the case because the HLA molecules are fairly specific. Removing the two anchor residues from each presented peptide, we find that the self:nonself overlap of these exposed 7-mers resembles that of 9-mers. Summarizing, the 9-mers used in MHC class I presentation tend to carry sufficient information to detect nonself peptides amongst self peptides.

Chromosome Research, 2011

As a mechanical system, the kinetochore can be viewed as a set of interacting springs, clutches a... more As a mechanical system, the kinetochore can be viewed as a set of interacting springs, clutches and motors; the problem of kinetochore mechanism is now one of understanding how these functional modules assemble, disassemble and interact with one another to give rise to the emergent properties of the system. The sheer complexity of the kinetochore system points to a future requirement for data-driven mathematical modelling and statistical analysis based on quantitative empirical measurement of sister kinetochore trajectories. Here, we review existing models of chromosome motion in the context of recent advances in our understanding of kinetochore molecular biology.

BMC Genomics, 2010

Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoe... more Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermentergrown samples.

Bioinformatics, 2010

Gene expression measurements are the most common data source for reverse engineering gene interac... more Gene expression measurements are the most common data source for reverse engineering gene interaction networks. When dealing with destructive sampling in time course experiments, it is common to average any available measurements for each time point and to treat this as the actual time series data for fitting the network, neglecting the variability contained in the repeated measurements. Proceeding in such a way can affect the retrieved network topology.

Applied and Environmental Microbiology, 2000

We observed the infection cycle of the temperate actinophage KC301 in relation to the growth of i... more We observed the infection cycle of the temperate actinophage KC301 in relation to the growth of its host Streptomyces lividans TK24 in sterile soil microcosms. Despite a large increase in phage population following germination of host spores, there was no observable impact on host population numbers as measured by direct plate counts. The only change in the host population following infection was the establishment of a small subpopulation of KC301 lysogens. The interaction of S. lividans and KC301 in soil was analyzed with a population-dynamic mathematical model to determine the underlying mechanisms of this low susceptibility to phage attack relative to aquatic environments. This analysis suggests that the soil environment is a highly significant component of the phage-host interaction, an idea consistent with earlier observations on the importance of the environment in determining host growth and phage-host dynamics. Our results demonstrate that the accepted phage-host interaction and host life cycle, as determined from agar plate studies and liquid culture, is sufficient for quantitative agreement with observations in soil, using soil-determined rates. There are four significant effects of the soil environment: (i) newly germinated spores are more susceptible to phage lysis than are hyphae of developed mycelia, (ii) substrate mycelia in mature colonies adsorb about 98% of the total phage protecting susceptible young hyphae from infection, (iii) the burst size of KC301 is large in soil (>150, 90% confidence) relative to that observed in liquid culture (120, standard error of the mean [SEM], 6), and (iv) there is no measurable impact on the host in terms of reduced growth by the phage. We hypothesize that spatial heterogeneity is the principal cause of these effects and is the primary determinant in bacterial escape of phage lysis in soil.