The interactions between Clostridium difficile, intestinal microbiota and the host response in hospitalised patients
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases
Abstract
Clostridium difficile is a bacterium that causes chronic diarrhoea and sometimes life-threatening disease (referred to as C. difficile infection or CDI) mainly in elderly and hospitalized patients. C. difficile is now the most significant hospital acquired infection with over 34,000 UK cases last year and an estimated cost to be £500 million per annum. The reported incidence of CDI has risen dramatically over the last decade and is related to the emergence of aggressive strains. Given the ability of C. difficile to evolve to be highly virulent coupled with the ageing population and increasing rates of hospitalization, the problem of CDI is likely to continue. It is a current NHS imperative to reduce the burden of CDI.
CDI is unique among infections in that in almost all cases, disease follows the administration of antibiotics that disrupt the "normal" bacteria (called microbiota) present in the gut. It provides C. difficile the opportunity to overgrow, produce toxins and cause disease. It has become apparent that the balance of the microbiota plays a key role in disease. One of the most perplexing questions concerning CDI is the diversity of clinical symptoms. For example, C. difficile colonization can result in a spectrum of clinical outcomes ranging from asymptomatic carriage to death. The relative virulence of C. difficile organism clearly plays a role in determining clinical outcome, but the nature of this role has not been identified. Up to 30% of patients treated successfully for symptomatic CDI succumb to recurrent disease, but it is unclear why only some patients relapse. In addition to the pathogen, the host immune response and/or host microbiota are also likely important determinants of clinical outcome, but remain largely unexplored. Our central hypothesis is that variations in C. difficile genetics, the composition of the resident intestinal microbiota and the host immune response to the bacterium shape the clinical outcome.
We will investigate the three-way interaction between pathogen, host and microbiota by monitoring a unique group of patients with and without CDI. C. difficile serum and faecal samples will be studied in unprecedented detail to provide a platform for follow up studies to understand how C. difficile causes disease. We have established a high quality prospectively collected bioarchive comprising bacterial, blood and serum samples from 300 patients with CDI and full clinical history. These samples are linked to detailed clinical data and a disease severity-scoring index along with 150 control samples from hospitalised patients who have been exposed to antibiotics but did not develop CDI. We will use the existing cohort to validate methodologies and then also recruit another cohort of 150 confirmed CDI cases, 100 diarrhoea controls and 100 healthy volunteers (e.g. patient's spouses) to confirm our findings. This unique resource will be used to monitor the host response (including how the immune system responds to the infection), determine the complete genome sequence of infecting C. difficile and identify the intestinal microbiota by sequencing and culturing. The studies will also allow us to distinguish between re-infection (infection caused by another strain) and relapse (re-infection caused by the same strain).
Robust statistical analysis comparing disease severity, host response, infecting pathogen and the composition of intestinal microbiota will facilitate subsequent studies on C. difficile to determine how and why it causes disease. This will be achieved by selecting C. difficile genes and constructing defined mutants and studying these alongside the parent strain in a range of assays established in the applicants' laboratories.
A comprehensive understanding of C. difficile, the host response and the intestinal microbiota will strengthen our understanding of the microorganism and to develop novel strategies to reduce the burden of CDI.
CDI is unique among infections in that in almost all cases, disease follows the administration of antibiotics that disrupt the "normal" bacteria (called microbiota) present in the gut. It provides C. difficile the opportunity to overgrow, produce toxins and cause disease. It has become apparent that the balance of the microbiota plays a key role in disease. One of the most perplexing questions concerning CDI is the diversity of clinical symptoms. For example, C. difficile colonization can result in a spectrum of clinical outcomes ranging from asymptomatic carriage to death. The relative virulence of C. difficile organism clearly plays a role in determining clinical outcome, but the nature of this role has not been identified. Up to 30% of patients treated successfully for symptomatic CDI succumb to recurrent disease, but it is unclear why only some patients relapse. In addition to the pathogen, the host immune response and/or host microbiota are also likely important determinants of clinical outcome, but remain largely unexplored. Our central hypothesis is that variations in C. difficile genetics, the composition of the resident intestinal microbiota and the host immune response to the bacterium shape the clinical outcome.
We will investigate the three-way interaction between pathogen, host and microbiota by monitoring a unique group of patients with and without CDI. C. difficile serum and faecal samples will be studied in unprecedented detail to provide a platform for follow up studies to understand how C. difficile causes disease. We have established a high quality prospectively collected bioarchive comprising bacterial, blood and serum samples from 300 patients with CDI and full clinical history. These samples are linked to detailed clinical data and a disease severity-scoring index along with 150 control samples from hospitalised patients who have been exposed to antibiotics but did not develop CDI. We will use the existing cohort to validate methodologies and then also recruit another cohort of 150 confirmed CDI cases, 100 diarrhoea controls and 100 healthy volunteers (e.g. patient's spouses) to confirm our findings. This unique resource will be used to monitor the host response (including how the immune system responds to the infection), determine the complete genome sequence of infecting C. difficile and identify the intestinal microbiota by sequencing and culturing. The studies will also allow us to distinguish between re-infection (infection caused by another strain) and relapse (re-infection caused by the same strain).
Robust statistical analysis comparing disease severity, host response, infecting pathogen and the composition of intestinal microbiota will facilitate subsequent studies on C. difficile to determine how and why it causes disease. This will be achieved by selecting C. difficile genes and constructing defined mutants and studying these alongside the parent strain in a range of assays established in the applicants' laboratories.
A comprehensive understanding of C. difficile, the host response and the intestinal microbiota will strengthen our understanding of the microorganism and to develop novel strategies to reduce the burden of CDI.
Technical Summary
Reduction in C. difficile infection (CDI) related morbidity and mortality is a current healthcare imperative. To develop appropriate sustained interventions, a holistic integrated view of the pathogen, the host response and the intestinal microbiota during infection is required. Our central hypothesis is that variation in C. difficile genetics, the composition of the resident intestinal microbiota and the repertoire of host factors, including the humoral immune response, shape the clinical outcome of CDI. To this end we will evaluate in unprecendented detail the pathogen genome sequence, intestinal microbial composition and the host response in a case-control study of CDI hospitalised patients. Rigorous statistical comparisons of data from the organism, intestinal microbiota and host response in relation to a patient disease severity index will enable selected genes/proteins to be chosen for functional analysis. To determine their role, defined/complemented mutants and wild type strains will be compared in several relevant in vivo-relevant assays. Potential biomarkers of disease severity will be assessed based on the combined clinical and molecular profile. Additionally, we will identify key bacterial groups important in re-establishing healthy microbiota during infection. Such analysis will investigate the role of the microbiota in providing colonisation resistance against CDI and will give new information on the bacterial species important in the re-establishment of healthy microbiota after infection, with applications in the rational design of microbial replacement therapy. This integrated clinical case control study will provide for the first time a comprehensive comparison of the pathogen, host response and the role of the intestinal microbiota in CDI that will afford new clues to pathogenesis with practical implications in terms of diagnosis and therapeutic interventions.
Planned Impact
C. difficile is now known to be the most frequent cause of hospital acquired infections in developed countries. Given the continued use of broad-spectrum antibiotics, other drugs and the rising numbers of immuno-compromised and elderly patients, the problems associated with CDI will remain a challenge to healthcare delivery for the foreseeable future. To date, most research on C. difficile has been piecemeal and has not taken into account the role of the microbiota and the host. This study will uniquely follow infection in a cohort of patients and be compared to appropriate controls. This multidisciplinary research programme fits squarely into several priority research areas identified by the MRC, in terms of reducing the burden of hospital acquired infections, health in the ageing population, the application of genomics, to the identification of biomarkers, drug and vaccine candidate and the design of novel treatments.
Given the mortality and morbidity caused by CDI and the enormous cost to the UK economy (estimated to be £500 million per annum), the benefits of improved methods to detect, prevent and understand CDI to health and wealth of society are self-evident. The commercial private sector will potentially benefit from the research in several areas. Specific examples include the investigation of the role of the healthy microbiota in providing colonisation resistance against CDI and will give new information on the bacterial species important in the re-establishment of a healthy microbiota after infection, with applications in the rational design of microbial replacement therapy. The identification of immunodominant antigens from samples of patient serum with the pan-C.difficile protein microarray may identify useful immunodiagnostic markers and provide information on potential vaccine candidates. A deeper understanding of the factors important during relapse may provide clues to novel strategies to curtail the effect of CDI. Given the healthcare issues surrounding hospital-acquired infections and the human microbiota, the project will also engage the public
Additionally, through these studies and our deeper understanding of CDI and recurrent disease, this is likely to influence policy makers and regulators as to the optimum treatment for CDI. C. difficile and CDI are very much in the public and political eye, the co-ordinated program of work described is unique and promises to break new ground in both basic and translational research. The research program should give the UK a significant boost in this important and topical health care issue and will contribute significantly to the UK science base.
Given the mortality and morbidity caused by CDI and the enormous cost to the UK economy (estimated to be £500 million per annum), the benefits of improved methods to detect, prevent and understand CDI to health and wealth of society are self-evident. The commercial private sector will potentially benefit from the research in several areas. Specific examples include the investigation of the role of the healthy microbiota in providing colonisation resistance against CDI and will give new information on the bacterial species important in the re-establishment of a healthy microbiota after infection, with applications in the rational design of microbial replacement therapy. The identification of immunodominant antigens from samples of patient serum with the pan-C.difficile protein microarray may identify useful immunodiagnostic markers and provide information on potential vaccine candidates. A deeper understanding of the factors important during relapse may provide clues to novel strategies to curtail the effect of CDI. Given the healthcare issues surrounding hospital-acquired infections and the human microbiota, the project will also engage the public
Additionally, through these studies and our deeper understanding of CDI and recurrent disease, this is likely to influence policy makers and regulators as to the optimum treatment for CDI. C. difficile and CDI are very much in the public and political eye, the co-ordinated program of work described is unique and promises to break new ground in both basic and translational research. The research program should give the UK a significant boost in this important and topical health care issue and will contribute significantly to the UK science base.
Publications
Knetsch CW
(2018)
Zoonotic Transfer of Clostridium difficile Harboring Antimicrobial Resistance between Farm Animals and Humans.
in Journal of clinical microbiology
Passmore IJ
(2018)
Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria.
in PLoS pathogens
Tosas Auguet O
(2018)
Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing Between Hospitals.
in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Ravenhall M
(2018)
Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.
in PLoS genetics
Portelli S
(2018)
Understanding molecular consequences of putative drug resistant mutations in Mycobacterium tuberculosis.
in Scientific reports
Ndila CM
(2018)
Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study.
in The Lancet. Haematology
Sobkowiak B
(2018)
Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data.
in BMC genomics
Coll F
(2018)
Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.
in Nature genetics
Sepúlveda N
(2018)
Global analysis of Plasmodium falciparum histidine-rich protein-2 (pfhrp2) and pfhrp3 gene deletions using whole-genome sequencing data and meta-analysis.
in Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
Benavente ED
(2018)
Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development.
in Scientific reports
Costa SS
(2018)
Genetic Diversity of norA, Coding for a Main Efflux Pump of Staphylococcus aureus.
in Frontiers in genetics
Richards E
(2018)
The S-layer protein of a Clostridium difficile SLCT-11 strain displays a complex glycan required for normal cell growth and morphology.
in The Journal of biological chemistry
Benavente E
(2018)
A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line
in International Journal for Parasitology
Palittapongarnpim P
(2018)
Evidence for Host-Bacterial Co-evolution via Genome Sequence Analysis of 480 Thai Mycobacterium tuberculosis Lineage 1 Isolates.
in Scientific reports
Andreu N
(2017)
Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
in Scientific reports
Browne HP
(2017)
Transmission of the gut microbiota: spreading of health.
in Nature reviews. Microbiology
Diez Benavente E
(2017)
Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure
in PLOS ONE
Trimarsanto H
(2017)
VivaxGEN: An open access platform for comparative analysis of short tandem repeat genotyping data in Plasmodium vivax populations.
in PLoS neglected tropical diseases
McNerney R
(2017)
Removing the bottleneck in whole genome sequencing of Mycobacterium tuberculosis for rapid drug resistance analysis: a call to action.
in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Dombrowski JG
(2017)
G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.
in Malaria journal
Cairns MD
(2017)
Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages.
in Journal of clinical microbiology
Jamille Dombrowski
(2017)
MOESM3 of G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon
Nakatani Y
(2017)
Role of Alanine Racemase Mutations in Mycobacterium tuberculosis d-Cycloserine Resistance.
in Antimicrobial agents and chemotherapy
Peltier J
(2017)
Disparate subcellular location of putative sortase substrates in Clostridium difficile.
in Scientific reports
Sengstake S
(2017)
Pyrazinamide resistance-conferring mutations in pncA and the transmission of multidrug resistant TB in Georgia.
in BMC infectious diseases
Campos MC
(2017)
Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole.
in Scientific reports
Gomes AR
(2017)
Genetic diversity of next generation antimalarial targets: A baseline for drug resistance surveillance programmes.
in International journal for parasitology. Drugs and drug resistance
Felgner J
(2017)
Development of ELISAs for diagnosis of acute typhoid fever in Nigerian children
in PLOS Neglected Tropical Diseases
Jamille Dombrowski
(2017)
MOESM1 of G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon
Cairns MD
(2017)
Correction for Cairns et al., "Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages".
in Journal of clinical microbiology
Jamille Dombrowski
(2017)
MOESM2 of G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon
Campino S
(2016)
Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines.
in Malaria journal
Valiente E
(2016)
Role of Glycosyltransferases Modifying Type B Flagellin of Emerging Hypervirulent Clostridium difficile Lineages and Their Impact on Motility and Biofilm Formation.
in The Journal of biological chemistry
Phelan JE
(2016)
Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages.
in BMC genomics
| Title | Additional file 10: Figure S9. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Non-neutral evolution for genes within Clusters of Orthologous Groups (COG*) categories. Boxplots are constructed using (-log10) p-values of non-neutral evolution for each gene. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 127Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_10_Figure_S9_of_Recombination_in... |
| Title | Additional file 10: Figure S9. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Non-neutral evolution for genes within Clusters of Orthologous Groups (COG*) categories. Boxplots are constructed using (-log10) p-values of non-neutral evolution for each gene. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 127Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_10_Figure_S9_of_Recombination_in... |
| Title | Additional file 2: Figure S1. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The global distribution of geographic origin and lineage of the isolates. Lineages one to four are represented by blue, green, purple, and red, respectively. (PNG 265 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of___Mycobacterium_t... |
| Title | Additional file 2: Figure S1. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The global distribution of geographic origin and lineage of the isolates. Lineages one to four are represented by blue, green, purple, and red, respectively. (PNG 265 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of___Mycobacterium_t... |
| Title | Additional file 2: Figure S1. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Allele frequency spectra for each lineage by synonymous (blue) and non-synonymous (red) mutations. The peaks at intermediate allele frequencies include sub-lineage defining SNPs (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). (TIF 207Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of_Recombination_in_... |
| Title | Additional file 2: Figure S1. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Allele frequency spectra for each lineage by synonymous (blue) and non-synonymous (red) mutations. The peaks at intermediate allele frequencies include sub-lineage defining SNPs (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). (TIF 207Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_2_Figure_S1_of_Recombination_in_... |
| Title | Additional file 3: Figure S2. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | SNP allele frequency spectrum. A large number of rare variants are observed. Peaks with higher allele frequency reflect the presence of lineage and sub-lineage specific SNPs. (PNG 33 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of___Mycobacterium_t... |
| Title | Additional file 3: Figure S2. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | SNP allele frequency spectrum. A large number of rare variants are observed. Peaks with higher allele frequency reflect the presence of lineage and sub-lineage specific SNPs. (PNG 33 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of___Mycobacterium_t... |
| Title | Additional file 3: Figure S2. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Gene-based nucleotide diversity (D ) for the 21 reference genomes. All genes with high nucleotide diversity (D â >â 0.0075) are labelled. (TIF 148Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of_Recombination_in_... |
| Title | Additional file 3: Figure S2. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Gene-based nucleotide diversity (D ) for the 21 reference genomes. All genes with high nucleotide diversity (D â >â 0.0075) are labelled. (TIF 148Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_3_Figure_S2_of_Recombination_in_... |
| Title | Additional file 4: Figure S3. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree constructed using 50,540 genome-wide SNPs. Clear clustering according to lineage can be seen (Lineage 1 (Indo-Oceanic, green), lineage 2 (East-Asian (Beijing), blue), lineage 3 (East-African-Indian, purple), lineage 4 (Euro-American, red)). Reference genomes are labelled. M. canetti is annotated in cyan. (TIF 69Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_4_Figure_S3_of_Recombination_in_... |
| Title | Additional file 4: Figure S3. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree constructed using 50,540 genome-wide SNPs. Clear clustering according to lineage can be seen (Lineage 1 (Indo-Oceanic, green), lineage 2 (East-Asian (Beijing), blue), lineage 3 (East-African-Indian, purple), lineage 4 (Euro-American, red)). Reference genomes are labelled. M. canetti is annotated in cyan. (TIF 69Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_4_Figure_S3_of_Recombination_in_... |
| Title | Additional file 5: Figure S4. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Identifying sites leading to differences in tree topologies based on all SNPs (Additional file 4: Figure S3a) and only those from pe/ppe genes (Additional file 4: Figure S3b). The Î Site wise log likelihood score (Î SSLS) is calculated for each SNP in the pe/ppe gene alignments. Negative differences indicate SNP positions favouring the pe/ppe tree. SNPs in pe_pgrs3, ppe57 and ppe60 produce strong phylogenetic signals supporting the pe/ppe tree. (TIF 113Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_5_Figure_S4_of_Recombination_in_... |
| Title | Additional file 5: Figure S4. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Identifying sites leading to differences in tree topologies based on all SNPs (Additional file 4: Figure S3a) and only those from pe/ppe genes (Additional file 4: Figure S3b). The Î Site wise log likelihood score (Î SSLS) is calculated for each SNP in the pe/ppe gene alignments. Negative differences indicate SNP positions favouring the pe/ppe tree. SNPs in pe_pgrs3, ppe57 and ppe60 produce strong phylogenetic signals supporting the pe/ppe tree. (TIF 113Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_5_Figure_S4_of_Recombination_in_... |
| Title | Additional file 6: Figure S5. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree created using only SNPs from pe_pgrs3. No clear clustering by lineage is observed. However there are two major clades, one consistent with H37Rv (bottom-left). (TIF 126Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_6_Figure_S5_of_Recombination_in_... |
| Title | Additional file 6: Figure S5. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Phylogenetic tree created using only SNPs from pe_pgrs3. No clear clustering by lineage is observed. However there are two major clades, one consistent with H37Rv (bottom-left). (TIF 126Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_6_Figure_S5_of_Recombination_in_... |
| Title | Additional file 7: Figure S6. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Molecular interactions established by wild-type residues in katG and rpoB residues. (A) The interactions established by Ser315 in katG. Given the proximity of the residue to the ligands INH and HEM, mutations to Asn and Thr, with slightly larger side chains, would potentially cause steric clashes. (B) The interactions of Asp435 in rpoB. It directly interacts with RMP via polar interactions that would be disrupted by mutations to Val. (C) Thr400 in rpoB is at the end of an alpha helix establishing intra molecular interactions. Giving its distance to RMP, it would be expected that its mutation to Ala would be a lower impact, which would arise from alosteric changes. (D) Ser450 establishes strong intra molecular interactions in the RMP binding site. Mutations to larger residues (Trp and Leu) could disrupt the packing of the region and therefore binding. (E). Ile491 performs hydrophobic interactions with RMP and its neighbouring residues. Mutations to Phe or Val would compromise packing, either inducing steric clashes or compromising packing. (F). His445 performs strong intra molecular interactions, including a donor-pi (blue dashes) and hydrogen bond (red dashes). Mutations to residues Asp, Tyr or Arg would imply in the loss of the pi interaction as well as potential introduction of steric clashes. (PNG 749 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of___Mycobacterium_t... |
| Title | Additional file 7: Figure S6. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Molecular interactions established by wild-type residues in katG and rpoB residues. (A) The interactions established by Ser315 in katG. Given the proximity of the residue to the ligands INH and HEM, mutations to Asn and Thr, with slightly larger side chains, would potentially cause steric clashes. (B) The interactions of Asp435 in rpoB. It directly interacts with RMP via polar interactions that would be disrupted by mutations to Val. (C) Thr400 in rpoB is at the end of an alpha helix establishing intra molecular interactions. Giving its distance to RMP, it would be expected that its mutation to Ala would be a lower impact, which would arise from alosteric changes. (D) Ser450 establishes strong intra molecular interactions in the RMP binding site. Mutations to larger residues (Trp and Leu) could disrupt the packing of the region and therefore binding. (E). Ile491 performs hydrophobic interactions with RMP and its neighbouring residues. Mutations to Phe or Val would compromise packing, either inducing steric clashes or compromising packing. (F). His445 performs strong intra molecular interactions, including a donor-pi (blue dashes) and hydrogen bond (red dashes). Mutations to residues Asp, Tyr or Arg would imply in the loss of the pi interaction as well as potential introduction of steric clashes. (PNG 749 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of___Mycobacterium_t... |
| Title | Additional file 7: Figure S6. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Lineage-specific recombination hotspots. Manhattan plots showing genes that are likely to be recombination hotspots in each lineage (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). The (â log10) p-value for the phi statistic is plotted against genome position. All genes with p-valuesâ |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of_Recombination_in_... |
| Title | Additional file 7: Figure S6. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Lineage-specific recombination hotspots. Manhattan plots showing genes that are likely to be recombination hotspots in each lineage (Lineage 1 Indo-Oceanic; Lineage 2 East-Asian (Beijing); Lineage 3 East-African-Indian; Lineage 4 Euro-American). The (â log10) p-value for the phi statistic is plotted against genome position. All genes with p-valuesâ |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_7_Figure_S6_of_Recombination_in_... |
| Title | Additional file 8: Figure S7. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Evidence of recombination at a gene level in the 21 reference genomes. A Manhattan plot showing genes that are likely to be recombination hotspots. The (â log10) p-value for the phi statistic is plotted against genome position. Genes with p-values less than 0.05 are shown. (TIF 120Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_8_Figure_S7_of_Recombination_in_... |
| Title | Additional file 8: Figure S7. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Evidence of recombination at a gene level in the 21 reference genomes. A Manhattan plot showing genes that are likely to be recombination hotspots. The (â log10) p-value for the phi statistic is plotted against genome position. Genes with p-values less than 0.05 are shown. (TIF 120Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_8_Figure_S7_of_Recombination_in_... |
| Title | Additional file 9: Figure S8. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Selection dN/dS values for each gene within Clusters of Orthologous Groups (COG*) categories. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 124Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_9_Figure_S8_of_Recombination_in_... |
| Title | Additional file 9: Figure S8. of Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Description | Selection dN/dS values for each gene within Clusters of Orthologous Groups (COG*) categories. *ppe/Nâ =â pe/ppe genes annotated as COG category N, * COG categories: A RNA processing and modification, B Chromatin Structure and dynamics, C Energy production and conversion, D Cell cycle control and mitosis, E Amino Acid metabolism and transport, F Nucleotide metabolism and transport, G Carbohydrate metabolism and transport, H Coenzyme metabolism, I Lipid metabolism, J Translation, K Transcription, L Replication and repair, M Cell wall/membrane/envelope biogenesis, N Cell motility, O Post-translational modification, protein turnover, chaperone functions, P Inorganic ion transport and metabolism, Q Secondary Structure, T Signal Transduction, U Intracellular trafficking and secretion, Y Nuclear structure, Z Cytoskeleton, R General Functional Prediction only, S Function Unknown. (TIF 124Â kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2016 |
| URL | https://springernature.figshare.com/articles/figure/Additional_file_9_Figure_S8_of_Recombination_in_... |
| Description | Academic Travel Award |
| Amount | £1,000 (GBP) |
| Organisation | Santander Universities |
| Sector | Private |
| Country | United Kingdom |
| Start | 02/2016 |
| End | 03/2016 |
| Description | Full PhD Fellowship |
| Amount | £125,000 (GBP) |
| Funding ID | #200974442 |
| Organisation | Government of Brazil |
| Department | Science without Borders |
| Sector | Public |
| Country | Brazil |
| Start | 09/2013 |
| End | 03/2017 |
| Description | LY256: A novel and potent antibiotic for treating Clostridium difficile infection |
| Amount | £1,729,174 (GBP) |
| Funding ID | MR/S019103/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2019 |
| End | 03/2023 |
| Description | Wellcome Trust Senior Investigator award |
| Amount | £2,100,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2014 |
| End | 04/2019 |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Additional file 3 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 3. All BLASTN hits from AaegL5 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Flavivirus_integrations_in... |
| Title | Additional file 3 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 3. All BLASTN hits from AaegL5 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_3_of_Flavivirus_integrations_in... |
| Title | Additional file 4 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 4. Accension IDs of all used flavivirus genomes. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Flavivirus_integrations_in... |
| Title | Additional file 4 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 4. Accension IDs of all used flavivirus genomes. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_of_Flavivirus_integrations_in... |
| Title | Additional file 4: Figure S3. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Population structure analysis of the 144 isolates show clustering by lineage (Lineages one to four are represented by blue, green, purple, and red points, respectively). (a) A phylogenetic tree rooted with M. canetti. (b) First two principal components represent 33Â % and 30.5Â % of the variation explained between isolates, respectively. (ZIP 105 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_Figure_S3_of___Mycobacterium_... |
| Title | Additional file 4: Figure S3. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Population structure analysis of the 144 isolates show clustering by lineage (Lineages one to four are represented by blue, green, purple, and red points, respectively). (a) A phylogenetic tree rooted with M. canetti. (b) First two principal components represent 33Â % and 30.5Â % of the variation explained between isolates, respectively. (ZIP 105 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_4_Figure_S3_of___Mycobacterium_... |
| Title | Additional file 5 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 5. All BLASTN hits from AaloF2 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Flavivirus_integrations_in... |
| Title | Additional file 5 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 5. All BLASTN hits from AaloF2 assembly. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_of_Flavivirus_integrations_in... |
| Title | Additional file 5: Figure S4. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The relationship between the total number of non-synonymous SNPs in candidate loci and the MIC values. The size of the circle represents the number of isolates. a) Ethambutol (embB, embA, embA promoter, embC, embR and ubiA). b) Streptomycin (rpsL, rrs). The size of the circles is proportional to the frequency. The MIC values tend to increase with the number of non-synonymous mutations (ethambutol: rho = 0.24, slope = 0.29, p = 0.003; streptomycin: rho = 0.48, slope = 3.59, p = 1.65 × 10-8). The horizontal blue lines refer to the resistance cut-offs. (ZIP 92 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_Figure_S4_of___Mycobacterium_... |
| Title | Additional file 5: Figure S4. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | The relationship between the total number of non-synonymous SNPs in candidate loci and the MIC values. The size of the circle represents the number of isolates. a) Ethambutol (embB, embA, embA promoter, embC, embR and ubiA). b) Streptomycin (rpsL, rrs). The size of the circles is proportional to the frequency. The MIC values tend to increase with the number of non-synonymous mutations (ethambutol: rho = 0.24, slope = 0.29, p = 0.003; streptomycin: rho = 0.48, slope = 3.59, p = 1.65 × 10-8). The horizontal blue lines refer to the resistance cut-offs. (ZIP 92 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_5_Figure_S4_of___Mycobacterium_... |
| Title | Additional file 6 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 6. EVE coordinates and sequences identified in AaloF2. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Flavivirus_integrations_in... |
| Title | Additional file 6 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 6. EVE coordinates and sequences identified in AaloF2. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_of_Flavivirus_integrations_in... |
| Title | Additional file 6: Figure S5. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Percentage of the variation in MIC values explained by each mutated codon in candidate genes. Bars in red represent significant independent associations with increased MIC (pâ |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_Figure_S5_of___Mycobacterium_... |
| Title | Additional file 6: Figure S5. of Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance |
| Description | Percentage of the variation in MIC values explained by each mutated codon in candidate genes. Bars in red represent significant independent associations with increased MIC (pâ |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_6_Figure_S5_of___Mycobacterium_... |
| Title | Additional file 7 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 7. EVE bedfiles for AaegL5 and AaloF2 assemblies; phylogenetic trees and corresponding metadata for Ae. aegypti EVEs and cox1 gene. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Flavivirus_integrations_in... |
| Title | Additional file 7 of Flavivirus integrations in Aedes aegypti are limited and highly conserved across samples from different geographic regions unlike integrations in Aedes albopictus |
| Description | Additional file 7. EVE bedfiles for AaegL5 and AaloF2 assemblies; phylogenetic trees and corresponding metadata for Ae. aegypti EVEs and cox1 gene. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/Additional_file_7_of_Flavivirus_integrations_in... |
| Title | MOESM1 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 1: Table S1. SNPs identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM1_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM1 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 1: Table S1. SNPs identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM1_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM2 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 2: Table S2. Insertions (INS) and deletions (DEL) identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM2_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM2 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 2: Table S2. Insertions (INS) and deletions (DEL) identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM2_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM3 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 3: Table S3. SNPs and Indels identified in the PF3D7_1222600 gene among P. falciparum field isolates from Africa and Asia. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM3_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM3 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 3: Table S3. SNPs and Indels identified in the PF3D7_1222600 gene among P. falciparum field isolates from Africa and Asia. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM3_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM4 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 4: Table S4. Structural variants identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM4_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM4 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 4: Table S4. Structural variants identified in the three lines 3D7A, A4 and F12. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM4_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM7 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 7: Table S5. A scan for motifs in gene sequences (coding and UTR regions). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM7_of_Genomic_variation_in_two_gametocyte_n... |
| Title | MOESM7 of Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines |
| Description | Additional file 7: Table S5. A scan for motifs in gene sequences (coding and UTR regions). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2016 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/dataset/MOESM7_of_Genomic_variation_in_two_gametocyte_n... |
| Title | Oligosaccharyltransferase Polypeptide |
| Description | New enzyme to improve glycoengineering in E. coli |
| IP Reference | GB1704103.9 |
| Protection | Patent application published |
| Year Protection Granted | 2018 |
| Licensed | Commercial In Confidence |
| Impact | Improve glycoengineering in the E. coli cell |
| Title | THERAPEUTIC FOR TREATING CLOSTRIDIUM DIFFICILE INFECTION |
| Description | The invention relates to deoxyribonuclease for use in the treatment of a suspected or existing C. difficile infection; a pharmaceutical or veterinary composition or formulation comprising at least deoxyribonucleasefor use in the treatment of a suspected or existing C. difficile infection; a combination therapeutic comprising at least deoxyribonucleasefor use in the treatment of a suspected or existing C. difficile infection; a method of treating a mammal suspected of being infected with, or infected with, C. difficile comprising the use of at least deoxyribonuclease; a method of cleaning or sterilising a material or product comprising the use of at least deoxyribonuclease; and a cleaning or sterilising product impregnated with or containing at least deoxyribonuclease. |
| IP Reference | WO2013175172 |
| Protection | Patent application published |
| Year Protection Granted | 2013 |
| Licensed | No |
| Impact | Simple treatment to reduce C. difficile disease |
| Description | 8th International Conference on the Molecular Biology and Pathogenesis of the Clostridia, 22-26th October 2013 (Andrew Swale and Fabio Miyajima) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Presentation of 2 posters which attracted significant attention from the audience. Interactions with several leading research groups represented in the field, access to most current expertise and trends in the field. Set up of strategic collaborations and access to new methodologies and materials, such as protein epitopes and immunogenic. |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.clostridia.net/ClostPath.htm |
| Description | 8th International Conference on the Molecular Biology and Pathogenesis of the Clostridia, 22-26th October 2013 -conference cast (Andrew Swale) |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Conference Cast made by Scitable (Nature education group) in which one of the members of the team (Andrew Swale: PhD Student) shared his experience related to his research and attendance at the 8th International Conference on the Molecular Biology and Pathogenesis of the Clostridia, 22-26th October 2013 in Australia. Provided further insights for postgraduate students about the conference experience for a junior researcher. Requests for further contributions have been made. |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.nature.com/scitable/blog/conferencecast/molecular_biology_pathogenesis_of_the |
| Description | BBC Breakfast |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Interview on Antibiotic resistance, Vaccine development and Government plans |
| Year(s) Of Engagement Activity | 2019 |
| Description | BBC News |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Interview on Antibiotic resistance, Vaccine development and Government plans |
| Year(s) Of Engagement Activity | 2019 |
| Description | Steering Committee Meeting on Clostridium difficile infection (Royal Liverpool and Broadgreen Hospitals - NHS Trust) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Our team is frequently invited to take part of the meetings and provide regular updates of our research findings to the committee. This interaction with NHS is highly beneficial for both parts and has assisted the Hospitals to shape their guidelines and keep CDI and other nosocomial infections under control. |
| Year(s) Of Engagement Activity | 2012,2013,2014,2015 |
| Description | TV Broadcasts |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | BBC Breakfast TV interview on vaccine design and antimicrobial resistance BBC one interview on Campylobacter in Food chain One Show BBC on antimicrobial resistance |
| Year(s) Of Engagement Activity | 2015 |
| Description | University Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | 50-60 prospective undergraduate students attended the University open day with their parents, relatives and friends, and paid a visit to our research facilities. This was an important initiative to attract future talents for the courses offered in the area of biomedical sciences and medicine and the event as a whole has certainly sparked further interest from the audience as courses have been well sought after. |
| Year(s) Of Engagement Activity | 2014,2015 |