Integrated genomic and proteomic characterisation of autotransporter proteins of obligate intracellular bacteria C. abortus and L. intracellularis

Lead Research Organisation: Moredun Research Institute
Department Name: Vaccines and Diagnostics

Abstract

Many infectious diseases affect livestock and impact not only on the health and welfare of animals but also on the economic sustainability of our agriculture industry. Among important animal pathogens are some bacteria that live within and are entirely dependent upon host cells. These so-called 'obligate intracellular' bacteria are very difficult to work with hence gaining understanding to aid in improving animal health is very problematic. Since this type of pathogen must infect a host animal to survive they typically develop mechanisms to very efficiently enter and take over host cells and evade the host's defences. Among the obligate intracellular bacteria, Chlamydophila abortus and Lawsonia intracellularis are very highly prevalent in sheep and pigs, respectively. Since such a high proportion of animals are affected, these infections have a considerable effect on animal health, quality of life and productivity. Although vaccines to these pathogens are available these have shortcomings so ultimately, we would like to develop efficient methods to very effectively reduce the effects of these diseases. Since these bacteria are difficult to work with, use of high-technology genomic methods can be very cost-effective and productive ways to improve the understanding of components with important roles in infection and make new developments in controlling disease. Genome sequences provide a wealth of information about pathogens and from this information we have identified a family of components - so-called Type V secretion proteins - which are likely to be involved in causing disease. Analysis of genomes is very informative however this is of greatest value when combined with an understanding of the function of the protein products of genes. We intend to study this family of proteins using computer-based approaches and laboratory methodologies to gain comprehension of these Type V proteins. These proteins are present on the surface of bacteria and, typically, are recognised by host defences and can result in the host activating defences that protect against infection. The ability to vary these proteins can be an important way to 'camouflage' pathogens allowing them to escape from host defences. Both C. abortus and L. intracellularis have many members of these Type V proteins thus we consider it is very likely that the members of this family present on the bacteria surface will vary. By gaining an understanding of how the presence of these proteins varies in each of these species we will be in a position to define the family members that are most important to infection and therefore lead to improved detection, treatment or prevention of these important livestock diseases.

Technical Summary

For many bacterial pathogens, proteins of the Type V secretion system play significant roles in pathogen-host interaction in respect of both pathogenicity and immunity. Members of this protein family are present in a wide diversity of bacteria including the obligate intracellular pathogens Chlamydophila abortus and Lawsonia intracellularis. These species' genomes carry contiguous loci comprising multiple proteins resembling Type V proteins which implies that carriage and/or expression may vary both within and among isolates. To test this hypothesis we will take complementary genomic and functional genomic approaches. Genome sequences for both of these pathogens will be subjected to detailed bioinformatics analyses for motifs representing the main subtypes of these proteins. This will refine the analyses carried out so far and identify any other members of this protein family potentially encoded by these genomes. Comparative genome analysis will be carried out at both intra- and inter-species levels by RFLP, genome hybridisation (microarray) and sequence analysis of the Type V loci from several isolates of these two species. To determine whether isolates vary in expression, candidates will be assessed using RT-PCR, proteomics and immunochemical approaches. To broaden the analysis of Type V protein carriage and expression a seroepidemiological survey of host species (sheep and pigs for C. abortus and L. intracellularis, respectively) will be conducted. This project will define whether Type V proteins of these bacteria impart heterogeneity to strains. This will substantially advance understanding of these important endemic livestock pathogens and make a significant contribution to the development of novel vaccines, diagnostics and epidemiological markers. Furthermore, this will add considerably to the understanding of the important Type V family of bacterial proteins.

Publications

10 25 50
publication icon
Bae JK (2013) Risk factors associated with Lawsonia intracellularis in English pig farms. in Veterinary journal (London, England : 1997)

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Entrican G (2012) New challenges for vaccination to prevent chlamydial abortion in sheep. in Comparative immunology, microbiology and infectious diseases

 
Description Infectious diseases affect livestock and impact not only on the health and welfare of animals but also on the economic sustainability of the agricultural industry. Among important animal pathogens are some bacteria that live within and are entirely dependent upon host cells. These so-called obligate intracellular bacteria are very difficult to work with, hence gaining understanding to aid in improving animal health is very problematic. Since this type of pathogen must infect a host animal to survive they typically develop mechanisms to very efficiently enter and take over host cells and evade the host's defences. Among the obligate intracellular bacteria, Chlamydophila abortus and Lawsonia intracellularis are very highly prevalent in sheep and pigs, respectively. Since such a high proportion of animals are affected, these infections have a considerable effect on animal health, quality of life and productivity.

Although vaccines to these pathogens are available these have shortcomings so ultimately, we would like to develop efficient methods to very effectively reduce the effects of these diseases. Since these bacteria are difficult to work with, use of high-technology genomic methods can be very cost-effective and productive ways to improve the understanding of components with important roles in infection and make new developments in controlling disease. Genome sequences provide a wealth of information about pathogens and from this information we have identified a family of components - so called Type V secretion proteins or autotransporter proteins - which are likely to be involved in causing disease. Analysis of genomes is very informative, however this is of greatest value when combined with an understanding of the function of the protein products of specific genes. During this project we have studied this family of proteins using computer-based approaches and laboratory methodologies to gain a better understanding of these Type V proteins and the role that they play in causing disease.



Autotransporter proteins are present on the surface of bacteria and, typically, are recognised by host defences and can result in the host activating defences that protect against infection. The ability to vary these proteins can be an important way to "camouflage" pathogens allowing them to escape from host defences. Both C. abortus and L. intracellularis have been found to have many members of these Type V proteins and analysis has shown that these proteins are localised to the organism surface. In addition the patterns of recognition of these proteins by the host immune response was found to vary at different time points during infection, suggesting that the organisms vary the presentation of these proteins on their surface as a means of avoiding host defences, thus making it easier for these pathogens to cause disease. A number of specific proteins from both organisms were identified as being particularly important to infection, either as proteins that can form the basis of new novel diagnostic tests or as candidates for inclusion in vaccine development studies, leading eventually to the improved detection, treatment or prevention of these important livestock diseases.



Key findings:

(i) Genomic sequencing, bioinformatic analysis and comparative genomics of the autotransporter proteins of both have revealed the identification of novel genes encoding putative autotransporter proteins. Findings suggest intraspecies heterogeneity is low, although overall intraspecies heterogeneity is high relative to the whole genome. No correlation was found in terms of host animal species or geographical origin. Heterogeneity is being investigated further in a new deep sequencing genome project, allowing more detailed comparative genomic analysis.

(ii) Identification of heterogeneity in autotransporter expression at both the genomic and proteomic level, suggestive of a role in antigenic diversity and immune evasion, and thus an important role in disease pathogenesis.

(iii) Identification of immunogenic autotransporter proteins through proteomic and immunoproteomic analyses, which are forming the basis for new novel diagnostic tests and as candidates for inclusion in vaccine development studies, leading eventually to the improved detection, treatment or prevention of these important livestock diseases. One test is currently being developed commercially.
Exploitation Route Identification of immunogenic autotransporter proteins through proteomic and immunoproteomic analyses, which are forming the basis for new novel diagnostic tests and as candidates for inclusion in vaccine development studies, leading eventually to the improved detection, treatment or prevention of these important livestock diseases. One test is currently being developed commercially.

Knowledge exchange and outreach are important activities for communication and promotion of scientific outputs to a variety of audiences. Communication with non-academic and non-research stakeholders have included a number of articles written for the farming and veterinary press, agricultural shows and liaising with government policy makers and potential industrial partners. These outputs have included 2 articles for the Sheep farmer (received by all members of the National Sheep Association), 2 articles for the Crofter magazine, a Moredun Foundation newsheet (mailed to the 10, 000 Moredun members), and a Moredun magazine article. The work investigating the heterogeneity of UK C. abortus isolates, which identified the abortifacient potential of the currently available EAE vaccine was subject to a press release. This was covered by a number of trade magazines and Newspapers including the Farmer's weekly, Veterinary Times, Press and Journal and The Scotsman, in addition to being carried by the BBSRC and Moredun websites. This work also led to a change in the packaging of the vaccine with its potential as an abortifacient added as an additional contraindication and this additional change was also made to the NOAH website.

A number of publications, providing specific technical advice on the management and control of C. abortus infection in sheep for farmers and veterinary surgeons, as well as potential zoonotic implications for humans for the public in general were written in reviews, articles and book chapters aimed at both scientific and non-scientific audiences. These included chapters on ovine enzootic abortion in the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals and on the therapeutics and control of sheep and goat diseases for Veterinary Clinics of North America: Food Animal Practice, both of which provide practical information and advice on the identification, diagnosis and control of the diseases.

In addition a number of presentations and attendances at agricultural events have been made during the course of the project. These include provision of expert advice at the National Sheep Association (NSA) Scotsheep (2010 and 2012), NSA national sheep event (2010), NSA Northern Ireland (2011) and the Royal Highland Show (2010, 2012). In addition presentations have been made to the Sheep Veterinary Society (2010) and during the Moredun Animal Health roadshows (2011). There has also been attendance and interactions with non-research stakeholders, including government, levy boards, industry and farmers, such as at the SAC pig event held at MRI in 2010, the Scottish Beef Cattle Society (2012), Scottish Government Programme stakeholder event days (2010, 2011), at quarterly Moredun Board meetings, at the annual CEDFAS grantholders workshops (2008, 2009, 2010) and at the CEDFAS Final Dissemination Event (2011).

Interactions with government, in addition to personal communications with members of RESAS, have included, Knowledge Scotland website updates on the progress and impact of research connected with this grant, as well as attendance on a Scottish Government work shadowing scheme (2012) to improve communication between scientists, government policy makers and advisers, influencing policy decisions and achieving a greater insight into the processes involved in determining and delivering policy. The Moredun open day in 2008 highlighting aspects of ongoing research was attended by members of the public, farming community, government and industry, as well as veterinarians, school teachers and school children. In addition presentations on the work of the Chlamydia group were made to Her Royal Highness the Princess Royal in both 2010 and 2011 during Royal visits to Moredun. Annual visits to speak to 5th/6th year pupils at an Edinburgh school to encourage and promote careers in science were also undertaken. New bioinformatic software tools for whole genome analysis and genome comparisons were developed in conjunction with the Moredun Bioinformatics Unit (MBU). These tools enabled multiple options for the visual display of the genomes sequenced during the project as well as colour coded displays indicating the level of conservation between genomic segments in multiple genome comparison views. For the proteomic analyses of both pathogens, new software tools were developed in collaboration with the MBU and Moredun Proteomics Facility (MPF) to facilitate the rapid interrogation of data from the mass spectrometer, in order to validate protein hits and thus identify the proteins present in a particular fraction being analysed. These software tools have been invaluable in for the rapid analysis of data sets and have been utilised by many groups within the organisation as well as for data analysis for external clients of the MPF.

Lawsonia intracellularis (Lic) is a fastidious organism, which is extremely difficult to grow and propagate, requiring specialist culture conditions, involving the use of hydrogen to purge tissue culture flasks upon infection of 20-30% confluent mammalian cells, followed by maintenance of flasks in an incubator under 8% oxygen and 8.8% CO2. As part of the work conducted under this project we have somewhat refined and simplified the methodology for growing this organism, following extensive investigations, with the major change being the replacement of the use of hydrogen gas with the addition of cysteine in the infection medium. This has made growth of the organism simpler and safer.

Genomic sequences for two variant strains of C. abortus (Cab) and for three subtypes of C. pecorum (for comparative purposes; as the only major chlamydial pathogen of ruminants yet to be sequenced and published), identified following genomic analysis and comparison of autotransporter (AT) protein genes with wild-type strains during this study, have been fully sequenced and annotated. The much larger genome of Lic type strain N343 has been sequenced for comparison with strain Phe/MN1-00, identifying little difference at the genomic level. All genomes have or will be deposited in public databases upon publication and provide a beneficial scientific resource for downstream comparative genomic and proteomic studies.

As a result of the collaboration with the Sanger Institute on this project, a much larger Cab Genome Sequencing Project was established at no additional cost, involving multi-collaborative international participation, mainly from colleagues in Europe. To date over 67 Cab strains have been isolated, grown and sequenced. The work is ongoing and due for completion early 2013, but will be a significant resource for the scientific community, allowing comparisons at the whole genome level, as well as allowing estimates of genomic heterogeneity, within key protein families (such as type III and type IV proteins) and across strains, which will be important for future control strategies. Based on phylogenetic analysis of single nucleotide polymorphisms (SNPs) within these sequences and cluster analysis, a new typing system has been developed for the genotypic classification of new isolates. As part of all this work new Cab isolates have been generated for genomic, proteomic and sequencing studies. A number of specific antibody reagents have been produced to both Cab and Lic AT proteins that have allowed analysis of the expression of these molecules under different experimental conditions, and comparing relative expression levels both within and across strains. Real time PCR assays have been developed in order to investigate the expression of AT proteins from both organisms at the transcriptional level, while recombinant protein constructs were produced for protein expression and immunological protein expression analysis. All of these reagents and constructs have been made freely available for other research groups to make use of.

While trying to identify new isolates of a bovine origin to fulfil the objectives of this project, new and novel organisms closely related to Chlamydia were identified following partial sequencing of 16S rRNA genes. These sequences (a total of 46), which have been detailed in a number of publications, have been submitted to GenBank and assigned accession numbers GQ919016-GQ919030 and HQ702405-HQ702436. Following on from this, as well as the new collaboration set up between ourselves and the Royal Veterinary College working on the CEDFAS PMWS project, we submitted an application to the BBSRC for a new 3 year project investigating the prevalence and pathogenesis of these organisms.

This application was submitted as an Industrial Partnership with Pfizer, as well as with the dairy sector levy board DairyCo. The application was successful and the project starts in January 2013.

Proteomic analysis of subcellular fractions of C. abortus while investigating the expression of autotransporter proteins in the outer membrane led to the discovery of a novel bacteriophage that infects the organism, this was published and the sequence submitted to GenBank and assigned accession number AY769964. This will provide a potential mechanism for the mutational analysis for studying gene function and hence identifying new and novel targets for future vaccine development studies.

No licences or patents have arisen so far from the work conducted in this project. However, following the identification of a protein fragment of one of the chlamydial polymorphic membrane proteins as being specific for identifying animals infected with C. abortus and not infected with another chlamydial species that commonly infects ruminants and pigs, C. pecorum, we obtained additional funding to develop this fragment into an enzyme-linked immunosorbent assay for serological detection of anti-C. abortus antibodies. Development of the test into a single well format is expected to be completed early in 2013, at which time it is expected that the test which is being manufactured by a company in Ireland, will be sold by a company based in Edinburgh under a licensing agreement with Moredun.

Proteomic and seroproteomic analysis of L. intracellularis membrane proteins have identified an immunogenic protein, termed LatA, as well as a number of other antigens. LatA has been characterised and suggested to be an autotransporter protein. This offers potential as a serodiagnostic reagent (which currently relies on whole bacterial antigen from culture), although the IP situation is limited by prior art. Nevertheless, the results have led to interest from a veterinary pharmaceutical company into the potential of this work leading to commercially viable diagnostic reagents and subunit vaccine components. This may result in future licensing agreements or patents.

During our investigations of new isolates obtained for this project, a number of isolates that originated from C. abortus vaccinated animals (an attenuated strain) that had aborted as a result of disease caused by this pathogen, revealed the identification of the vaccine in the diseased placentas, suggesting an association with the disease. This was the first report of the live vaccine potentially causing disease and has important implications for the animal health companies that market the two live vaccines. This has led to a collaborative agreement between us and the two animal health companies that manufacture the vaccine to investigate this further.
Sectors Agriculture, Food and Drink,Environment

URL http://www.moredun.org.uk/research/research-%40-moredun/reproductive-diseases/chlamydia/genome-project
 
Description Discussions have been ongoing with Industrial partner A regarding exploitation of Lawsonia intracellularis outer membrane proteins, characterised as part of this project utilising proteomic techniques, as possible vaccine and diagnostic candidate antigens. Explorative discussions with an industrial company regarding the identification of potential vaccine candidate antigens through the work conducted on this project, and possible exploitation through future collaborative funding opportunities. However to date this has not evolved in any tangible additional collaborative opportunities, plus the PI involved in this work has now left the organisation so it is unlikely that this will progress in the short to medium term. Evidence provided in previous work as well as more thorough analysis of the immune response to the chlamydial polymorphic membrane proteins conducted as part of this project has identified one particular protein that is suitable for identifying animals infected with Chlamydia abortus. Additional funding was obtained from Genecom and internal Moredun Innovation Funds to commercially develop and exploit these findings in the form of a new diagnostic ELISA. The work was done in collaboration with Industrial Partner B. Additional Innovate UK funding (£25k) was sought and awarded to take the test through to commercialisation in collaboration with Partner B who would be responsible for marketing the new test and Industrial Partner C who would be responsible for producing the test. The test is now available commercially for purchase.
First Year Of Impact 2012
Sector Agriculture, Food and Drink,Education,Environment
Impact Types Economic

 
Description Development of a novel commercial serological ELISA for diagnosing animals infected with Chlamydia abortus
Amount £15,000 (GBP)
Funding ID P903 
Organisation GeneCom Group 
Sector Private
Country United States
Start 07/2011 
End 06/2012
 
Description Development of a novel commercial serological ELISA for diagnosing animals infected with Chlamydia abortus
Amount £25,805 (GBP)
Funding ID 265 
Organisation Moredun Research Institute 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2011 
End 06/2012
 
Description Emerging chlamydia-like organisms as novel causes of bovine reproductive failure
Amount £614,816 (GBP)
Funding ID BB/J015083/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2013 
End 02/2016
 
Title Complete genome sequence of Lawsonia intracellularis strain N343 
Description Completed the draft sequence and annotation of the L. intracellularis strain N343 for comparison with strain Phe/MN1-00. To be deposited in GenBank and published. 
Type Of Material Biological samples 
Year Produced 2013 
Provided To Others? Yes  
Impact Genome sequence provides essential information for the identification of novel diagnostic and vaccine candidates through antigen discovery programmes 
URL http://www.ncbi.nlm.nih.gov/nuccore/CP004029
 
Title Generation of antibodies against C. abortus Pmps 
Description To investigate the expression of C. abortus Pmps antibodies have been raised against specific peptides or recombinant proteins. For several of the Pmps antibodies have been raised against different domains to enable studies into processing of individual proteins. To date 20 antibodies have been raised and validated. They have been analysed to ensure that there is no cross-reactivity against other Pmps. 
Type Of Material Antibody 
Year Produced 2013 
Provided To Others? Yes  
Impact Antibodies useful for the identification of chlamydial pmps for immunoproteomic studies 
 
Title Generation of antibodies against surface proteins of Lawsonia Intracellularis 
Description To investigate the expression of L. intracellularis autotransporter proteins antibodies were gnerated against 2 autotransporters (demonstrated to be expressed through proteomic analysis) and 3 additional outer membrane proteins. Antibodies were raised against specific peptides and validated against recombinant proteins. 
Type Of Material Antibody 
Year Produced 2012 
Provided To Others? Yes  
Impact Identification of immunoreactive antigens for diagnostic development and as vaccine candidates. 
 
Title Complete genome sequence of Lawsonia intracellularis strain N343 
Description Completed the draft sequence and annotation of the L. intracellularis strain N343 for comparison with strain Phe/MN1-00. To be deposited in GenBank and published. 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact Genome sequence provides essential information for the identification of novel diagnostic and vaccine candidates through antigen discovery programmes 
URL http://www.ncbi.nlm.nih.gov/nuccore/CP004029
 
Description Association of Chlamydia-like organisms with cases of bovine abortion 
Organisation DairyCo
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution These collaborations, some existing, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.
Start Year 2008
 
Description Association of Chlamydia-like organisms with cases of bovine abortion 
Organisation Pfizer Ltd
Department Pfizer Animal Health
Country Global 
Sector Private 
PI Contribution These collaborations, some existing, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.
Start Year 2008
 
Description Association of Chlamydia-like organisms with cases of bovine abortion 
Organisation Scotland's Rural College
Country United Kingdom 
Sector Academic/University 
PI Contribution These collaborations, some existing, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.
Start Year 2008
 
Description Association of Chlamydia-like organisms with cases of bovine abortion: collaboration with AHVLA 
Organisation Animal Health And Veterinary Laboratories Agency (AHVLA)
Country United Kingdom 
Sector Public 
PI Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Collaborator Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Impact Joint publications and conference presentations
Start Year 2010
 
Description Association of Chlamydia-like organisms with cases of bovine abortion: collaboration with Lausanne 
Organisation University of Lausanne
Country Switzerland 
Sector Academic/University 
PI Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.
Start Year 2010
 
Description Association of Chlamydia-like organisms with cases of bovine abortion: collaboration with Royal Vetinary College 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.
Start Year 2010
 
Description Association of Chlamydia-like organisms with cases of bovine abortion: collaboration with University of Lausanne, Switzerland 
Organisation Lausanne University Hospital (CHUV)
Country Switzerland 
Sector Hospitals 
PI Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Collaborator Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Impact Exchange of reagents and biological samples. Joint publications and conference presentations.
Start Year 2010
 
Description Association of Chlamydia-like organisms with cases of bovine abortion: collaboration with Zurich 
Organisation University of Zurich
Country Switzerland 
Sector Academic/University 
PI Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Collaborator Contribution These collaborations, some exisiting, which now include SAC, AHVLA, the University of Zurich, the University of Lausanne and the Royal Veterinary College were started as a result of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application, on which we continue to collaborate and exchange reagents and biological samples
Impact Exchange of reagents and biological samples. Joint publications and conference presentations.
Start Year 2010
 
Description Chlamydial genome sequencing project - collaboratiion with dIstituito Zooprofilattico Sperimentale della Lombardia e dell? Emilia Romagna 
Organisation Lombardy and Emilia Romagna Experimental Zootechnic Institute (IZSLER)
Country Italy 
Sector Public 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaborating with Friedrich-Loeffler Institute 
Organisation Friedrich Loeffler Institute
Country Germany 
Sector Public 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaborating with Pasteur Institute 
Organisation Pasteur Institute, Paris
Country France 
Sector Academic/University 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaborating with University College Dublin 
Organisation University College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaborating with University of Murcia 
Organisation University of Murcia, Spain
Country Spain 
Sector Academic/University 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaborating with Wellcome Trust Sanger Institute 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaboration with Aristotle University of Thessaloniki 
Organisation Aristotle University of Thessaloniki
Country Greece 
Sector Academic/University 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Chlamydial genome sequencing project - collaboration with China Agricultural University 
Organisation China Agricultural University (CAU)
Country China 
Sector Academic/University 
PI Contribution To allow genomic comparisons to be made between different C. abortus and C. pecorum strains, DNA has been obtained from isolates from international and local sources. As sequencing technologies have evolved since the initial submission of the project, whole genomes are being sequenced and assembled and comparisons are being made at the whole genome level rather then restricted to the Pmp regions or by employing microarray (Objectives 5 and 4). This collaborative Genome Sequencing Project was agreed between Moredun and The Wellcome Trust Sanger Institute and evolved as a consequence of this grant.
Start Year 2008
 
Description Emerging Chlamydial-like organisms as novel causes of bovine reproductive failure 
Organisation Pfizer Ltd
Country United Kingdom 
Sector Private 
PI Contribution Following on from the identification of these novel chlamydia-like organisms in this project, as well as the new collaboration set up between ourselves and the Royal Veterinary College working on the CEDFAS PMWS project, partnership discussions were held with Pfizer to commit funding to an IPA application for submission to the BBSRC in October 2011 for a new 3 year project investigating the prevalence and pathogenesis of these organisms. Pfizer committed 10% of the total funding and the application was submitted in October 2011. The application was successful.
Start Year 2011
 
Description Evidence of Chlamydophila abortus vaccine strain 1B as a possible cause of Ovine Enzootic Abortion 
Organisation Animal Health And Veterinary Laboratories Agency (AHVLA)
Country United Kingdom 
Sector Public 
PI Contribution This study was an international collaboration led by ourselves at MRI and involving SAC and the Agence Francaise de Sécurité Sanitaire des Aliments (AFSSA) which demonstrated the potential of the current commercially licenced vaccine as a potential abortifacient agent. The work has led subsequently to the development of a screening program with the commercial pharmaceutical companies which produce the vaccine, SAC and AHVLA.
Start Year 2009
 
Description Evidence of Chlamydophila abortus vaccine strain 1B as a possible cause of Ovine Enzootic Abortion 
Organisation French Agency for Food Safety (AFSSA)
Country France 
Sector Public 
PI Contribution This study was an international collaboration led by ourselves at MRI and involving SAC and the Agence Francaise de Sécurité Sanitaire des Aliments (AFSSA) which demonstrated the potential of the current commercially licenced vaccine as a potential abortifacient agent. The work has led subsequently to the development of a screening program with the commercial pharmaceutical companies which produce the vaccine, SAC and AHVLA.
Start Year 2009
 
Description Industrial consultancy to investigate the incidence of commercial vaccine induced abortion in the UK 
Organisation Ceva Animal Health
Country United Kingdom 
Sector Private 
PI Contribution Consultancy/collaborative agreement put in place for us to investigate cases of abortion submitted to one of the regional veterinary centres in England/Wales through the Animal Health Veterinary Laboratory Agency and in Scotland through the Scottish Agricultural College on behalf of Ceva Animal Health one of the producers of the commercial live enzootic abortion of ewes vaccine.
Start Year 2010
 
Description Industrial consultancy to investigate the incidence of commercial vaccine induced abortion in the UK 
Organisation MSD Animal Health
Country United Kingdom 
Sector Private 
PI Contribution Consultancy/collaborative agreement put in place for us to investigate cases of abortion submitted to one of the regional veterinary centres in England/Wales through the Animal Health Veterinary Laboratory Agency and in Scotland through the Scottish Agricultural College on behalf of MSD Animal Health one of the producers of the commercial live enzootic abortion of ewes vaccine.
Start Year 2010
 
Description Pathogenesis of L. intracellularis and C. abortus strains in host species 
Organisation Moredun Research Institute
Department Pathology Unit
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Animal models have been used to determine the disease causing potential of different strains of both L. intracellularis and C. abortus in their natural host species, pigs and sheep respectively. This work is in the process of being written as a manuscript. It also enabled the formation of close working links with the Pathology unit at MRI. This link has led to various collaborations which have produced publications and a successful grant application.
Start Year 2008
 
Description Phylogenetic analysis of autotransporter proteins of L. intracellularis and C. abortus 
Organisation Biomathematics and Statistics Scotland (BioSS)
Country United Kingdom 
Sector Public 
PI Contribution To analyse the diversity of autotransporter proteins in the two bacterial species phylogenetic analysis (both within individual genomes and between strains/species) is being undertaken in collaboration with BIOSS. This work so far has helped identify variation in C.abortus Pmps and to investigate the evolution of this group of proteins. Work on L. intracellularis putative autotransporters revealed that the structure of many of these proteins encoded on plasmids differ significantly from traditional autotransporters in other species of bacteria. The work has also led to a significant collaboration in the investigations into Chlamydia-like organisms, with several publications and a successul grant application.
Start Year 2008
 
Description Proteomic analysis of L. intracellularis and C. abortus 
Organisation Moredun Research Institute
Department Moredun Proteomic Facility Services
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Outer membrane preparations have been generated for both C. abortus and L. intracellularis for which the manuscripts are in preparation. Autotransporter proteins, the subject of this grant, have ben identified as major components of the chlamydial membrabe and also present in the outer membrane of Lawsonia. Proteomic analysis has been carried out in collaboration with the Moredun Proteomics facility using protocols that have been jointly developed. In addition the facility has validated all recombinant protein constructs that have been generated as part of this project (23 to date)
Start Year 2008
 
Description Provision of Lawsonia intracellularis strains, DNA & sera 
Organisation University of Minnesota
Country United States 
Sector Academic/University 
PI Contribution L. intracellularis is a fastidious obligately intracellular bacterial pathogen and, worldwide, few laboratories have the capability to culture this bacterium reliably. There are few strain archives and the Gebhart laboratory holds one of these. Archived culture material for five L. intracelularis strains was obtained along with some samples of sera from naturally-infected animals. The strains originating from the USA were received as inactivated cultures and could not be cultured to increase their yields. UK isolate stocks were also replenished and culture has been intermittently successful. The materials obtained have been used for preparation of DNA and protein fractions. Aliquots of these samples have been analysed and the results bioninformatically analysed to determine the extent of expression of autotransporters and other outer membrane proteins. The analyses have been performed on multiple strains to determine whether there is variation in protein expression between strains. In addition serum samples from control and infected animals have been analysed against the different protein extracts to determine if there is variation in the immunogenicity of proteins between strains.
Start Year 2008
 
Description Seroepidemiological analysis of Lawsonia intracellularis in UK pigs collaboration between ourselves and both Prof Werling and Dr Barbara Wieland at the Royal Veterinary College 
Organisation Royal Veterinary College (RVC)
Country United Kingdom 
Sector Academic/University 
PI Contribution As a consequence of the CEDFAS meeting at Crewe Hall in June 2010, and following discussions regarding the pig PMWS CEDFAS project, a new collaboration was set up between ourselves the Royal Veterinary College to utilise the pig sera that they had collected for their project to investigate the seroprevalence of Lawsonia in pigs in the UK. This new collaboration has resulted in the submission of a publication.
Start Year 2010
 
Description Surface expression of autotransporter proteins of C. abortus and L. intracellularis in E.coli 
Organisation University of Birmingham
Country United Kingdom 
Sector Academic/University 
PI Contribution Autotransporter proteins of both C. abortus and L. intracellularis were modified to maximise their expression in E. coli. This was done in collaboration with Dr Ian Henderson, a world expert on the expression of autotransporter proteins. Good expression of the C. abortus polymorphic membrane protein was observed and shown to be expressed on the surface of E. coli, in contrast with Lawsonia where expression was poor. Surface expression is currently being confirmed by electron microscopy prior to publication.
Start Year 2008
 
Description Annual CEDFAS dissemination workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact CEDFAS dissemination workshop for grant holders to communicate background, objectives, project results and outcomes, as well impact, future plans and challenges.

no actual impacts realised to date
Year(s) Of Engagement Activity 2008,2009,2010
 
Description BBSRC CEDFAS dissemination event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Final BBSRC grantholders workshop and dissemination event held in London to discuss results and outputs of project "Integrated genomic and proteomic characterisation of autotransporters of C. abortus & L. intracellularis". Included participants from BBSRC, industry, levy boards, scientific and public domains and bodies.
Year(s) Of Engagement Activity 2011
 
Description BBSRC CEDFAS final dissemination event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact CEDFAS dissemination workshop for grant holders to communicate background, objectives, project results and outcomes, as well impact, future plans and challenges to key stakeholders including, scientific audience, government/policy makers, BBSRC, and others involved in the animal health industry.
Year(s) Of Engagement Activity 2011
 
Description Chlamydia Genome Sequencing Project 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact To highlight the ongoing work and disseminate the results of the chlamydial whole genome sequencing (Objectives 4 and 5) freely accessible websites have been developed at both Moredun and the Sanger Institutes Websites highlighting the ongoing work,

http://www.sanger.ac.uk/resources/downloads/bacteria/chlamydophila-abortus.html

no actual impacts realised to date
Year(s) Of Engagement Activity 2008,2009,2010,2011,2012
URL http://www.moredun.org.uk/research/research-%40-moredun/reproductive-diseases/chlamydia/genome-proje...
 
Description Development of SOSPArator software for analysis of proteomic data 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact SOSPArator software was developed at Moredun by scientists in the Bioinformatics Unit specifically for helping in the analysis of data eminating from the proteomic analysis of complex protein mixtures. The results of the proteomic analyses of both Chlamydia and Lawsonia conducted under this project were used in the development and validation of this software. Software development

no actual impacts realised to date
Year(s) Of Engagement Activity 2009
 
Description EU COST Action workshop on serological detection of chlamydial pathogens (Athens, Greece) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited presentation at a European COST Action workshop on the diagnosis of chlamydial infections in animals and birds, which included some of the work on the proteins that are the subject of this project

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description European Buiatrics Conference (Marseille, France) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Networking and promotion of our investigations and results of the initial work on trying to identify C. abortus infected cattle tissue to provide isolates for objectives 4 and 5 of the CEDFAS grant at the European Buiatrics Conference in Marseille, France. This initial work has led to a great deal of international interest in this area of research which has resulted in several publications and a successful BBSRC IPA grant application with Pfizer animal health and DairyCo as industrial partners.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description European Chlamydia conference (Jena, Germany) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation paper presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The work highlighted the presence and possible causal role of novel Chlamydia-like organisms in bovine abortion material isolated from multiple sources. Oral presentation: Evidence of the association of Chlamydia-like organisms with cases of cattle abortion in the UK.

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
 
Description European Meeting on Animal Chlamydioses (Jena, Germany) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on work involving genotyping of Chlamydia abortus by PCR targeting single nucleotide polymorphisms identified from whole genome sequencing. Engagement with colleagues working in similar field to stimulate discussion, ideas and collaboration. Led to some new areas of investigation and stimulated new ideas and direction.
Year(s) Of Engagement Activity 2013
 
Description European Meeting on Animal Chlamydioses (Murcia, Spain) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Oral presentation on the outcome of work investigating the genetic diversity and variability in the genes of the polymorphic membrane proteins (pmps) of 52 strains of C. abortus, originating from cases of fetal loss from various geographical regions and host species (sheep, goat and cow). Analysis found that there was greater variability in some pmps compared to others (genotype). No correlation could be made between genotype, host species or geographical origin except for two Greek strains, which formed a discrete genotype in all pmp-encoding regions (5 regions encompassing 18 genes) except one. Findings suggest that although intraspecies heterogeneity of pmp-encoding genes in C. abortus is low, the sequence heterogeneity should be an important consideration when using pmps as the basis for novel diagnostics or vaccine development.

no actual impacts realised to date
Year(s) Of Engagement Activity 2009
 
Description European Meeting on Animal Chlamydioses (Murcia, Spain) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation paper presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact To disseminate results of a study investigating the transcriptional analysis of in vitro expression patterns of Chlamydophila abortus polymorphic outer membrane proteins during the chlamydial developmental cycle. Provoked lots of interest and questions on our work on these proteins and their role in immune evasion as well as the aims and objectives of the BBSRC project.

no actual impacts realised to date
Year(s) Of Engagement Activity 2009
 
Description European Society for Chlamydia Research conference (Aarhus, Denmark) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientific Committee discussions on goals and aspirations for future European Meetings on Animal Chlamydioses and Zoonotic Infections

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description European Society for Chlamydia Research conference (Amsterdam, The Netherlands) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk aimed at disseminating outputs from the project and demonstrating evidence of the association of Chlamydia-like organisms with cases of bovine abortion in the UK

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description European Society for Chlamydia Research conference (Amsterdam, The Netherlands) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral presentation at the 7th Meeting of the European Society for Chlamydia Research on the comparative genomic analysis of three Chlamydia pecorum strains associated with different disease manifestations.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description European Society for Chlamydia Research conference (Amsterdam, The Netherlands) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation workshop facilitator
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Oral presentation at the 7th Meeting of the European Society for Chlamydia Research on the processing of Chlmaydia abortus polymorphic membrane protein 18D during the chlamydial developmental cycle.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description European Society of Clinical Microbiology and Infectious Diseases Technical Workshop (Villars-sur-Ollon, Switzerland) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Special lecturer for the workshop of the ESCMID Study group for Coxiella, Anaplasma, Rickettsia and Bartonella (ESCAR) on Intracellular Bacteria: from Biology to Clinic. Gave lecture on the importance of Pmps in chlamydial pathogenesis, which included discussion of the results and outputs from this grant.
Year(s) Of Engagement Activity 2013
 
Description European Society of Clinical Microbiology and Infectious Diseases Technical Workshop(Villars-sur-Ollon, Switzerland) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Special lecturer for the workshop of the ESCMID Study group for Coxiella, Anaplasma, Rickettsia and Bartonella (ESCAR) on Intracellular Bacteria: from Biology to Clinic. Gave lecture on the Genomics of Chlamydial species, which included discussion of the results and outputs from this grant.
Year(s) Of Engagement Activity 2013
 
Description Evidence of Chlamydophila abortus vaccine strain 1B as possible cause of ovine enzootic abortion 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Presentation describing the results of the pre-screen of potential new isolates from Scottish flocks (Spring 2009) prior to sequence analysis (Objectives 4 and 5). This presentation was made to staff of MRI, Moredun Scientific and AHVLA and provided relevent information to those of them that speak directly to stakeholders

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description First BBSRC CEDFAS grant holders workshop (Manchester, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact First BBSRC grantholders workshop held in Manchester to discuss progress and future goals of the project. This was a presentation to the 2008 CEDFAS workshop describing the recent findings of the grant "Integrated genomic and proteomic characterisation of autotransporters of C. abortus & L. intracellularis" to other grant holders, the steering group committee and invited guests and speakers, including members of the BBSRC.
Year(s) Of Engagement Activity 2008
 
Description German Chlamydia conference (Ulm, Germany) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecture at the annual German Chlamydia Conference in Ulm, Germany. Covered some of the work conducted under this grant on the pathogenesis of C. abortus infection in sheep.

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description Industry engagement (MSD Animal Health) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Face to face discussions with senior representative from MSD (Intervet) Animal Health from Milton Keynes, UK, regarding the findings of our work on the identification of their commercial vaccine strain in cases of abortion, as identified during the analysis of new chlamydial field isolates obtained for this project.

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Institute seminar (Edinburgh, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Talk on our identification of the association of Chlamydia-related organisms with cases of bovine abortion in the UK through our BBSRC CEDFAS project and how this led to new BBSRC IPA to study their prevalence, pathogenesis and role in bovine reproductive loss.
Year(s) Of Engagement Activity 2012
 
Description Institute talk on diversity, global impact and control of chlamydial infections 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Oral presentation to staff and visitors to the Institute on the spread and impact of chlamydial infections in both humans and animals, with specific aims and reference to the work being done at Moredun on understanding the pathogenesis of chlamydial infections in farm livestock, including work on the proteins that are the focus of this project towards improved methods of controlling infection through diagnosis and vaccination.

no actual impacts realised to date
Year(s) Of Engagement Activity 2009
 
Description Internal seminar (Edinburgh, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Seminar on the first identification of new chlamydial organisms in cases of bovine abortion in the UK. These organisms were identified directly as a result of work funded under this project to generate new isolates.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description Invited talk (Napier University, Edinburgh, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact An invited seminar in which the diversity of chlamydial infections was introduced to a mixed audience of students and staff members at Napier University. The talk highlighted C. abortus and the work being carried out on the BBSRC CEDFAS grant on the Pmps, their potential diagnostic use and possibilities in vaccine design. The talk also stimulated discussion on vaccine safety in light of the work on vaccine breakdown and potential drawbacks of live vaccines.

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Moredun Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Organiser for the bacteriology division promoting the work of the division to the public, stakeholders, government representatives, scientists, veterinarians, farmers, teachers, school children etc. Specifically promoted bacterial diseases, including disease management, vaccine and diagnostic control options, as well as a range of demonstrations and talks.

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description National Symposium on Zoonoses Research (Berlin, Germany) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited keynote speaker at German National Symposium in Berlin: Diversity, impact and control of chlamydial infections in ruminants. Gave lecture on the work we are doing on the pathogenesis and control of C. abortus in sheep, including aspects of the work completed as part of this project.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description National farming events 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research or patient groups
Results and Impact Providing technical advice on Chlamydia abortus infection in sheep to farmers and veterinary surgeons. Disseminating published experimental results to the non-academic audience and placing it in a practical perspective Updated leaflets on sheep abortion caused by Chlamydia abortus infection

Updated Moredun Foundation technical newsheet on ovine abortion caused by Chlamydia abortus infection

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Patent Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Third sector organisations
Results and Impact Workshop organised by Genecom, our Business Development Body, on the patenting process for protecting and exploiting Intellectual Property

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description Policy briefing 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This is a policy briefing aimed at highlighting the current knowledge on C. abortus infection in sheep including vaccine safety and the paucity of sound diagnostic reagents. The briefing also includes a section on the current work of Moredun in this area including the work on next generation diagnostics and sub-unit vaccines.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description Press release - chlamydia vaccine causes abortion 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact As part of our work on the BBSRC CEDFAS project to identify new chlamydia strains to look at variation in the polymorphic membrane protein genes and products we identified strains that originated from aborted animals that had been vaccinated. These strains proved to be identical to the commercial vaccine strains, which led to us conducting some work to show that the vaccine strains were responsible for the abortions, thus have the potential to cause disease in some animals. In view of the sensitive nature of this discovery we spoke with the vaccine companies prior to submission of our manuscript and issued a press release stating that we believe farmers should continue to use the vaccine until such time that an improved one was developed.
Year(s) Of Engagement Activity 2010
URL http://www.moredun.org.uk/news/scientists-urge-farmers-continue-vaccinating-even-through-new-researc...
 
Description Royal Visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Demonstration, posters and discussion with HRH The Princess Royal, Patron of Moredun at her annual visit to the institute on the work we are doing towards understanding the pathogenesis of chlamydial infections in sheep, as well as improved methods for diagnosis and vaccination. This included reporting and discussion on the proteins and findings associated with this project.

no actual impacts realised to date
Year(s) Of Engagement Activity 2011
 
Description Science Promotion in school 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Promotion of a career in science to 6th Year Pupils at a school in Edinburgh, using specific examples of work conducted under this grant

no actual impacts realised to date
Year(s) Of Engagement Activity 2008,2009,2010
 
Description Scottish Government stakeholder event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientific presentation on approaches taken for controlling chlamydial infection in sheep, including work conducted under this project, to key stakeholder groups, organised for the Scottish Government

no actual impacts realised to date
Year(s) Of Engagement Activity 2008
 
Description Second BBSRC CEDFAS grant holders workshop (Cheshire, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Second BBSRC grantholders workshop held in Cheshire to discuss progress and future goals of the project. This was a presentation to the 2009 CEDFAS workshop describing the recent findings of the grant "Integrated genomic and proteomic characterisation of autotransporters of C. abortus & L. intracellularis" to other grant holders, the steering group committee and invited guests and speakers, including members of the BBSRC.

no actual impacts realised to date
Year(s) Of Engagement Activity 2009
 
Description Sheep Veterinary Society invited presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an invited oral presentation to the Sheep Veterinary Society which was timed to coincide with the release of the related manuscript and a press release about the results of the study which suggested the current live vaccine may induce abortion, as discovered as part of work under this CEDFAS initiative. The talk was to an audience of sheep veterinarians and provided them with information which could be passed on to the farming community and avoid sensationalisation of the results.

Abstract published in the Proceedings of the Sheep Veterinary Society v34

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Talk to EBLEX on Control of chlamydial infections in sheep and cattle 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussions with EBLEX regarding possible funding opportunities to take the work generated from this project forward, particularly with regard to improved serodiagnostics and novel vaccination strategies

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
 
Description Third BBSRC CEDFAS grant holders workshop (Cheshire, UK) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Third BBSRC grantholders workshop held at Crewe Hall in Cheshire to discuss progress and future goals of the project. This was a presentation to the 2010 CEDFAS workshop describing the recent findings of the grant "Integrated genomic and proteomic characterisation of autotransporters of C. abortus & L. intracellularis" to other grant holders, the steering group committee and invited guests and speakers, including members of the BBSRC.

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description Vaccination to protect against enzootic abortion of ewes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Face to face discussions with senior representative from MSD (Intervet) Animal Health from Boxmeer, The Netherlands regarding the findings of our work on the identification of their commercial vaccine strain in cases of abortion, as identified during the analysis of new chlamydial field isolates obtained for this project.

no actual impacts realised to date
Year(s) Of Engagement Activity 2010
 
Description World Buiatrics Congress (lisbon, Portugal) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited oral presentation at the 27th World Buiatrics Congress 2012: Evidence of the association of Chlamydia-like organisms with cases of bovine abortion. Despite the worldwide economic importance and welfare issues associated with infectious bovine abortifacients, as well as potential zoonotic threats posed to human health, diagnosis of the causes of abortion remains poor. This could in part be explained by the presence of unidentified infectious abortifacient agents. Recently several novel species of Chlamydia-like organisms (CLOs) including Parachlamydia acanthamoebae have emerged as putative ruminant abortifacients, as well as involved in cases of respiratory infections and miscarriage in humans. The aim of this study was to investigate whether such organisms are present in cases of bovine abortion in the UK.

no actual impacts realised to date
Year(s) Of Engagement Activity 2012
URL http://books.google.co.uk/books/about/Proceedings.html?id=PJo2mwEACAAJ&redir_esc=y