ORCID Profile
0000-0002-5264-0929
Current Organisation
University of Nottingham
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Genomics | Bioinformatics | Genetics
Publisher: Cold Spring Harbor Laboratory
Date: 21-08-2020
DOI: 10.1101/2020.08.18.20174623
Abstract: In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on in iduals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected in idual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea – also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger s le of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.
Publisher: F1000 Research Ltd
Date: 14-05-2021
DOI: 10.12688/WELLCOMEOPENRES.16631.1
Abstract: We present a genome assembly from an in idual female Aquila chrysaetos chrysaetos (the European golden eagle Chordata Aves Accipitridae). The genome sequence is 1.23 gigabases in span. The majority of the assembly is scaffolded into 28 chromosomal pseudomolecules, including the W and Z sex chromosomes.
Publisher: Cold Spring Harbor Laboratory
Date: 13-09-2021
DOI: 10.1101/2021.09.13.459777
Abstract: The ongoing SARS-CoV-2 pandemic has demonstrated the utility of real-time analysis of sequencing data, with a wide range of databases and resources for analysis now available. Here we show how the real-time nature of Oxford Nanopore Technologies sequencers can accelerate consensus generation, lineage and variant status assignment. We exploit the fact that multiplexed viral sequencing libraries quickly generate sufficient data for the majority of s les, with diminishing returns on remaining s les as the sequencing run progresses. We demonstrate methods to determine when a sequencing run has passed this point in order to reduce the time required and cost of sequencing. We extended MinoTour, our real-time analysis and monitoring platform for nanopore sequencers, to provide SARS-CoV2 analysis using ARTIC network pipelines. We additionally developed an algorithm to predict which s les will achieve sufficient coverage, automatically running the ARTIC medaka informatics pipeline once specific coverage thresholds have been reached on these s les. After testing on run data, we find significant run time savings are possible, enabling flow cells to be used more efficiently and enabling higher throughput data analysis. The resultant consensus genomes are assigned both PANGO lineage and variant status as defined by Public Health England. S les from within in idual runs are used to generate phylogenetic trees incorporating optional background s les as well as summaries of in idual SNPs. As minoTour uses ARTIC pipelines, new primer schemes and pathogens can be added to allow minoTour to aid in real-time analysis of pathogens in the future. Source code and documentation is available at github.com/LooseLab/minotourapp . Supplementary data are available from github.com/LooseLab/artic_minotour_analyses .
Publisher: Springer Science and Business Media LLC
Date: 25-08-2023
Publisher: Springer Science and Business Media LLC
Date: 07-10-2011
DOI: 10.1007/S00285-011-0468-7
Abstract: Stochastic phenomena in gene regulatory networks can be modelled by the chemical master equation for gene products such as mRNA and proteins. If some of these elements are present in significantly higher amounts than the rest, or if some of the reactions between these elements are substantially faster than others, it is often possible to reduce the master equation to a simpler problem using asymptotic methods. We present ex les of such a procedure and analyse the relationship between the reduced models and the original.
Publisher: Microbiology Society
Date: 06-2021
DOI: 10.1099/JGV.0.001595
Abstract: In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on in iduals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected in idual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV-2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea – also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger s le of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2019
Publisher: Springer Science and Business Media LLC
Date: 30-01-2019
DOI: 10.1038/S41467-019-08387-8
Abstract: High-resolution molecular programmes delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are largely inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and of epiblast and hypoblast in late blastocysts. We show that following an emergent short naive pluripotent signature in early embryos, there is a protracted appearance of a primed signature in advanced embryonic stages. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.
Publisher: Cold Spring Harbor Laboratory
Date: 20-06-2018
DOI: 10.1101/347823
Abstract: High-resolution molecular programs delineating the cellular foundations of mammalian embryogenesis have emerged recently. Similar analysis of human embryos is limited to pre-implantation stages, since early post-implantation embryos are inaccessible. Notwithstanding, we previously suggested conserved principles of pig and human early development. For further insight on pluripotent states and lineage delineation, we analysed pig embryos at single cell resolution. Here we show progressive segregation of inner cell mass and trophectoderm in early blastocysts, and then of epiblast and hypoblast in late blastocysts. We detected distinct pluripotent states, first as a short ‘naïve’ state followed by a protracted primed state. Dosage compensation with respect to the X-chromosome in females is attained via X-inactivation in late epiblasts. Detailed human-pig comparison is a basis towards comprehending early human development and a foundation for further studies of human pluripotent stem cell differentiation in pig interspecies chimeras.
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2017
DOI: 10.1101/211466
Abstract: Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus free or to have only exogenous variants of KoRV with low rates of KoRV induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV induced disease such as lymphoma. This paper uses a combination of sequencing technologies, Illumina RNA sequencing of “southern” (south Australian) and “northern” (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of “southern” (South Australian and Victorian animals) to retrieve full length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication competent KoRV, are not in fact KoRV free but harbour defective, presumably endogenous, “RecKoRV” variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV induced disease.
Publisher: Cold Spring Harbor Laboratory
Date: 03-05-2018
DOI: 10.1101/312256
Abstract: The Oxford Nanopore Technologies (ONT) MinION is used for sequencing a wide variety of s le types with erse methods of s le extraction. Nanopore sequencers output fast5 files containing signal data subsequently base called to fastq format. Optionally, ONT devices can collect data from all sequencing channels simultaneously in a bulk fast5 file enabling inspection of signal in any channel at any point. We sought to visualise this signal to inspect challenging or difficult to sequence s les, or where flow cell performance is modified by an external agent, such as ‘Read Until’. The BulkVis tool can load a bulk fast5 file and overlays MinKNOW classifications on the signal trace. Users can navigate to a channel and time or, given a fastq header from a read, jump to its specific position. BulkVis can export regions as Nanopore base caller compatible reads. Using BulkVis, we find long reads can be incorrectly ided by MinKNOW resulting in single DNA molecules being split into two or more reads. The longest seen to date is 2,272,580 bases in length and reported in eleven consecutive reads. We provide helper scripts that identify and reconstruct split reads given a sequencing summary file and alignment to a reference. We note that incorrect read splitting appears to vary according to input s le type and is more common in ‘ultra long’ read preparations. The software is available freely under an MIT license at github.com/LooseLab/bulkVis . The software requires python3 to run.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2023
DOI: 10.1101/2023.04.28.538769
Abstract: 2. Repeat spill over of SARS-CoV-2 into new hosts has highlighted the critical role of cross species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spill-over include Mustelidae (mink, ferrets and related animals) and cricetid rodents (hamsters and related animals). These predispositions led us to screen British wildlife with sarbecovirus specific qPCR and pan coronavirus PCR assays for SARS-CoV-2 using s les collected during the human pandemic to establish if widespread spill-over was occurring. Fourteen wildlife species (n=402) were tested, including : 2 Red Foxes ( Vulpes vulpes ), 101 Badgers ( Meles meles ), 2 wild American Mink ( Neovison vison ), 41 Pine Marten ( Martes martes ), 2 Weasels ( Mustela nivalis ), 7 Stoats ( Mustela erminea ), 108 Water Voles ( Arvicola hibius ), 39 Bank voles ( Myodes glareolous ), 10 Field Voles ( Microtus agrestis ), 15 Wood Mice ( Apodemus sylvaticus ), 1 Common Shrew ( Sorex aranaeus ), 2 Pygmy Shrews ( Sorex minutus ), 2 Hedgehogs (Erinaceus europaeus ) and 75 Eurasian Otters ( Lutra lutra ). No cases of SARS-CoV-2 were detected in any animals, however a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
Publisher: Springer Science and Business Media LLC
Date: 25-01-2013
DOI: 10.1007/S11538-013-9811-Z
Abstract: Hybrid models for gene expression combine stochastic and deterministic representations of the underlying biophysical mechanisms. According to one of the simplest hybrid formalisms, protein molecules are produced in randomly occurring bursts of a randomly distributed size while they are degraded deterministically. Here, we use this particular formalism to study two key regulatory motifs-the autoregulation loop and the toggle switch. The distribution of burst times is determined and used as a basis for the development of exact simulation algorithms for gene expression dynamics. For the autoregulation loop, the simulations are compared to an analytic solution of a master equation. Simulations of the toggle switch reveal a number of qualitatively distinct scenarios with implications for the modelling of cell-fate selection.
Publisher: Microbiology Society
Date: 14-06-2023
DOI: 10.1099/JGV.0.001859
Abstract: Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV and SARS-CoV- 2. Despite the devastating impact of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species ( Rhinolophus hipposideros and R. ferrumequinum ) present in Great Britain, collected in 2021–22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros s les from 33 roost sites and 277 R . ferrumequinum s les from 20 roost sites were tested. No coronaviruses were detected in any s les from R. ferrumequinum whereas 44 and 56 % of in idual and pooled (respectively) faecal s les from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive s les (and partial genomes from two more) using Illumina RNAseq on unenriched s les. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with % similarity to previously-reported European isolates from R. hipposideros . The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros . Despite frequently sharing roost sites with R. ferrumequinum , no evidence of cross-species transmission was found.
Publisher: Cold Spring Harbor Laboratory
Date: 27-04-2020
DOI: 10.1101/2020.04.24.058164
Abstract: We have sequenced the genome of grass pea ( Lathyrus sativus ), a resilient diploid (2n=14) legume closely related to pea ( Pisum sativum ). We determined the genome size of the sequenced European accession (LS007) as 6.3 Gbp. We generated two assemblies of this genome, i) EIv1 using Illumina PCR-free paired-end sequencing and assembly followed by long-mate-pair scaffolding and ii) Rbp using Oxford Nanopore Technologies long-read sequencing and assembly followed by polishing with Illumina paired-end data. EIv1 has a total length of 8.12 Gbp (including 1.9 billion Ns) and scaffold N50 59,7 kbp. Annotation has identified 33,819 high confidence genes in the assembly. Rbp has a total length of 6.2 Gbp (with no Ns) and a contig N50 of 155.7 kbp. Gene space assessment using the eukaryote BUSCO database showed completeness scores of 82.8 % and 89.8%, respectively.
Publisher: Cold Spring Harbor Laboratory
Date: 14-02-2023
DOI: 10.1101/2023.02.14.528476
Abstract: Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV-1 and 2. Despite the devastating impacts of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species ( Rhinolophus hipposideros and R. ferrumequinum ) present in Great Britain, collected in 2021-22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros s les from 33 roost sites and 277 R. ferremequinum s les from 20 roost sites were tested. No coronaviruses were detected in any s les from R. ferrumequinum whereas 44% and 56% of in idual and pooled (respectively) faecal s les from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive s les (and partial genomes from two more) using Illumina RNAseq on unenriched s les. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with % similarity, as previously reported European isolates from R. hipposideros . The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros . Despite frequently sharing roost sites with R. ferrumequinum , no evidence of cross-species transmission was found.
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
DOI: 10.1038/S41586-020-2547-7
Abstract: After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist 1,2 . Here we present a human genome assembly that surpasses the continuity of GRCh38 2 , along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome 3 , we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis liconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.
Publisher: Cold Spring Harbor Laboratory
Date: 03-02-2020
DOI: 10.1101/2020.02.03.926956
Abstract: Nanopore sequencers enable selective sequencing of single molecules in real time by in idually reversing the voltage across specific nanopores. Thus DNA molecules can be rejected and replaced with new molecules enabling targeted sequencing to enrich, deplete or achieve specific coverage in a set of reads to address a biological question. We previously demonstrated this method worked using dynamic time warping mapping signal to reference, but required significant compute and did not scale to gigabase references. Using direct base calling with GPU we can now scale to gigabase references. We enrich for specific chromosomes mapping against the human genome and we develop pipelines enriching low abundance organisms from mixed populations without prior knowledge of s le composition. Finally, we enrich panels including 25,600 exon targets from 10,000 human genes and 717 genes implicated in cancer. Using this approach we identify PML-RARA fusions in the NB4 cell line in under 15 hours sequencing. These methods can be used to efficiently screen any target panel of genes without specialised s le preparation using a single computer and suitably powerful GPU.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2023
DOI: 10.1038/S41467-023-36503-2
Abstract: Grass pea ( Lathyrus sativus L.) is a rich source of protein cultivated as an insurance crop in Ethiopia, Eritrea, India, Bangladesh, and Nepal. Its resilience to both drought and flooding makes it a promising crop for ensuring food security in a changing climate. The lack of genetic resources and the crop’s association with the disease neurolathyrism have limited the cultivation of grass pea. Here, we present an annotated, long read-based assembly of the 6.5 Gbp L. sativus genome. Using this genome sequence, we have elucidated the biosynthetic pathway leading to the formation of the neurotoxin, β-L-oxalyl-2,3-diaminopropionic acid (β-L-ODAP). The final reaction of the pathway depends on an interaction between L. sativus acyl-activating enzyme 3 (LsAAE3) and a BAHD-acyltransferase (LsBOS) that form a metabolon activated by CoA to produce β-L-ODAP. This provides valuable insight into the best approaches for developing varieties which produce substantially less toxin.
Publisher: Cold Spring Harbor Laboratory
Date: 12-2021
DOI: 10.1101/2021.12.01.470722
Abstract: Adaptive s ling enables selection of in idual DNA molecules from sequencing libraries, a unique property of nanopore sequencing. Here we develop our adaptive s ling tool readfish to become “barcode-aware” enabling selection of different targets within barcoded s les or filtering out in idual barcodes. We show that multiple human genomes can be assessed for copy number and structural variation on a single sequencing flow cell using s le specific customised target panels on both GridION and PromethION devices.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2011
DOI: 10.1007/S00285-011-0433-5
Abstract: Gene expression at the single-cell level incorporates reaction mechanisms which are intrinsically stochastic as they involve molecular species present at low copy numbers. The dynamics of these mechanisms can be described quantitatively using stochastic master-equation modelling in this paper we study a generic gene-expression model of this kind which explicitly includes the representations of the processes of transcription and translation. For this model we determine the generating function of the steady-state distribution of mRNA and protein counts and characterise the underlying probability law using a combination of analytic, asymptotic and numerical approaches, finding that the distribution may assume a number of qualitatively distinct forms. The results of the analysis are suitable for comparison with single-molecule resolution gene-expression data emerging from recent experimental studies.
Publisher: Springer Science and Business Media LLC
Date: 09-12-2019
DOI: 10.1038/S41592-019-0697-Z
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2017
DOI: 10.1038/NATURE22401
Publisher: Elsevier BV
Date: 02-2021
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2018
DOI: 10.1101/459529
Abstract: High throughput cDNA sequencing technologies have dramatically advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and because modifications are not carried forward in cDNA. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies (ONT). Our study focused on poly(A) RNA from the human cell line GM12878, generating 9.9 million aligned sequence reads. These native RNA reads had an aligned N50 length of 1294 bases, and a maximum aligned length of over 21,000 bases. A total of 78,199 high-confidence isoforms were identified by combining long nanopore reads with short higher accuracy Illumina reads. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes from nanopore RNA data. Together, these nanopore-based techniques are poised to deliver new insights into RNA biology. MA holds shares in Oxford Nanopore Technologies (ONT). MA is a paid consultant to ONT. REW, WT, TG, JRT, JQ, NJL, JTS, NS, AB, MA, HEO, MJ, and ML received reimbursement for travel, accommodation and conference fees to speak at events organised by ONT. NL has received an honorarium to speak at an ONT company meeting. WT has two patents (8,748,091 and 8,394,584) licensed to Oxford Nanopore. JTS, ML and MA received research funding from ONT.
Publisher: Cold Spring Harbor Laboratory
Date: 12-09-2021
DOI: 10.1101/2021.09.10.459783
Abstract: MinoTour offers a LIMS system for Oxford Nanopore Technology (ONT) sequencers, with real-time metrics and analysis available permanently for review. Integration of unique real-time automated analysis can reduce the time required to answer biological questions, including mapping and classification of sequence whilst a run is in progress. Real-time sequence data requires new methods of analysis which do not wait for the completion of a run and MinoTour provides a framework to allow users to exploit these features. Source code and documentation are available at github.com/LooseLab/minotourcli and github.com/LooseLab/minotourapp . Docker images are available from /adoni5/ , and can be installed using a preconfigured docker-compose script at github.com/LooseLab/minotour-docker . An ex le server is available at 137.44.59.170 .
Publisher: Microbiology Society
Date: 28-06-2022
DOI: 10.1099/JGV.0.001749
Abstract: Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus-free or to have only exogenous variants of KoRV with low rates of KoRV-induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV-induced disease such as lymphoma. In this study we use a combination of sequencing technologies, Illumina RNA sequencing of ‘southern’ (south Australian) and ‘northern’ (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of ‘southern’ (South Australian and Victorian animals) to retrieve full-length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication-competent KoRV, are not in fact KoRV-free but harbour defective, presumably endogenous, ‘RecKoRV’ variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV-induced disease.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2020
DOI: 10.1101/2020.08.22.20176834
Abstract: COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.
Publisher: Wiley
Date: 06-2007
DOI: 10.1002/9780470151808.SC01D01S1
Abstract: Controlled differentiation of pluripotential cells takes place routinely and with great success in developing vertebrate embryos. It therefore makes sense to take note of how this is achieved and use this knowledge to control the differentiation of embryonic stem cells (ESCs). An added advantage is that the differentiated cells resulting from this process in embryos have proven functionality and longevity. This unit reviews what is known about the embryonic signals that drive differentiation in one of the most informative of the vertebrate animal models of development, the hibian Xenopus laevis . It summarizes their identities and the extent to which their activities are dose‐dependent. The unit details what is known about the transcription factor responses to these signals, describing the networks of interactions that they generate. It then discusses the target genes of these transcription factors, the effectors of the differentiated state. Finally, how these same developmental programs operate during germ layer formation in the context of ESC differentiation is summarized. Curr. Protoc. Stem Cell Biol. 1:1D.1.1‐1D.1.22. © 2007 by John Wiley & Sons, Inc.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2017
End Date: 12-2019
Amount: $419,500.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: Australian Research Council
View Funded Activity